bioworld - Medical Device Daily

BIOWORLD ® 

& MEDICAL DEVICE DAILY 

OBESITY REPORT: 

TIPPING THE MARKET 

SCALES WITH BIOTECH & 

MED-TECH REGIMENS 

2010 

THE BIOWORLD AND MEDICAL DEVICE DAILY OBESITY REPORT 1

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THE BIOWORLD ® AND MEDICAL DEVICE DAILY 

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THE BIOWORLD AND MEDICAL DEVICE DAILY OBESITY REPORT 

OBESITY REPORT: TIPPING THE MARKET SCALES WITH BIOTECH & MED-TECH REGIMENS 

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THE BIOWORLD AND MEDICAL DEVICE DAILY OBESITY REPORT

TABLE OF CONTENTS 

13 An Abstract Analysis: Obesity Treatment and Trends, Today and Tomorrow 

13 Atlas Shrugged . . . and Slumped Under the Weight of a Global Epidemic 

14 Obesity Can't Be Cured, Resolved or Wished Away by Re-defining it 

15 Drugs and Devices in the Obesity's Market's Growing Future 

17 The Overweight Population . . . Epidemic, Risk Factor or Misdiagnosis? 

22 Obesity Challenges Are Smoking for a Dubious Title 

22 Childhood Obesity Is Dooming a Generation Before it Gets Started 

23 A World Equally Hungry and Overfed 

27 Does the BMI Contrive an Artificial Market for Drug Developers, Med-tech 

Purveyors and Physicians? 

29 Does BMI Settle the Debate, or Is the Visual Proof All Around Us? 

29 We Won't Stop Eating, So We Must Keep Researching 

29 Sex, Sleep and Weight . . . Prurient Interests Augment Serious Markets 

30 The Weight of the World to Come: Challenges and Issues of the Future Market 

33 Obesity Drugs: An Underweight Market Seeks Big Opportunites from a 

Growing Problem 

35 Top Obesity Candidates Reveal Promising Data, but Get No Promises from 

Pharma 

38 Solving the Obesity Compound Conundrum: Where’s Big Pharma? 

39 How Much Longer? Pharma Resists the Lure of an Underserved 

Goldmine Market 

40 Combination Drugs Could Deliver Twice the Efficacy and Billions in 

Market Potential 

41 Arena Pharmaceuticals – lorcaserin 

44 Vivus – Qnexa 

48 Orexigen Therapeutics – Contrave 

50 Novo Nordisk – Victoza 

50 Alizyme – cetilistat 

51 Amylin Pharmaceuticals – pramlintide and metreleptin 

51 Obecure – Histalean 

52 Orexigen Therapeutics – Empatic 

53 NeuroSearch – tesofensine 

53 Surface Logix – SLx-4090 

53 Arete Therapeutics – AR9281 

53 Shionogi – S-2367 

53 Amylin Pharmaceuticals and Takeda Pharmaceutical – davalintide 

53 TransTech Pharma – TTP435 

54 7TM Pharma – TM30339 

54 7TM Pharma – Obinepitide (TM30338) 

54 OSI Pharmaceuticals – PSN821 

54 OSI Pharmaceuticals – PSN602 

54 AstraZeneca – AZD4017 


6 



54 Emisphere Technologies – Oral Peptide YY (PYY) 

54 TransTech Pharma – HPP404 

54 Surface Logix – SLx-2119 

55 Zafgen – ZGN-433 

55 Early Stage Development Efforts in Obesity 

55 7TM Pharma – TM38837 

55 Aegis Therapeutics 

55 Agios Pharmaceuticals 

55 AstraZeneca 

55 BioVista 

56 Braasch Biotech 

56 Cambridge Biotechnology / Proximagen Neuroscience 

56 CeNeRx BioPharma 

56 Colby Pharmaceutical – CPC-410 

56 Compellis Pharmaceuticals – CP404 

56 Corcept Therapeutics – CORT 108297 

57 DeveloGen 

57 Elixir Pharmaceuticals 

57 Fasgen 

57 Genfit – TGFTX2 

58 Halsa Pharmaceuticals – ZAG 

58 Intercept Pharmaceuticals – INT-777 

58 Isis Pharmaceuticals 

58 Marcadia Biotech 

58 Merck 

59 Myriad Pharmaceuticals – MPI-0485520 

59 Palatin Technologies 

59 RXi Pharmaceuticals 

59 Sirona Biochem 

60 Transition Therapeutics 

60 Unigene Laboratories – UGP281 

60 Ventana Biotech 

60 Xenon Pharmaceuticals 

60 XOMA – XOMA 052 

60 Zealand Pharma – ZP2929 

60 ZenBio 

61 Znomics 

61 Discontinued Products and Programs Are Prevalent in Obesity Space 

61 Athersys – ATHX-105 

61 Genaera – MSI-1436 

61 MDRNA – PPY(3-36) 


62 Merck – taranabant 

62 Neurogen – NGD-4715 

62 Orexigen Therapeutics – OREX-003 

63 Pfizer – CP-945,598 

63 Sanofi-Aventis – Acomplia 

63 Vernalis – V24343 

65 Unfortunately, It's a Growth Market: 

Limitless Opportunity Seen in Obesity Devices 

65 Devices Hold Top Market Billing Over Pharma Solutions for Obesity 

67 Benefits of Bariatric Surgery for the Morbidly Obese 

67 Bariatric Surgery Meets Cost Effectiveness Standards 

67 Bariatric Surgery Coverage Is Clarified 

68 Study: Bariatric Surgery as Safe for Teens as it Is for Adults 

69 Economics, Diabetes and Bariatric Surgery 

70 Revision Surgery Is a New Market 

71 USGI Medical – IOP 

72 C.R. Bard – EndoCinch 

73 EndoGastric Solutions – StomaphyX 

73 Adjustable Gastric Bands Fill Need, Face Market Risk 

74 Allergan – Lap-Band 

76 Ethicon Endo-Surgery – Realize 

77 Gastric Bypass vs. Gastric Band 

78 Less-Invasive Products Are New Market Segments for Bariatric Surgery 

78 Minimally Invasive Procedures 

78 GI Dynamics – EndoBarrier 

80 Satiety – TOGA 

81 USGI Medical – IOP 

81 Silhouette Medical – nObese 

82 Endosphere 

82 BAROnova – TransPyloric Shuttle 

82 ValenTx 

82 Other Surgical Platforms 

82 SafeStitch Medical 

83 TransEnterix – Spider System 

83 EndoVx 

83 Neuromodulation Is an Emerging Market 

83 EnteroMedics – Vbloc 

87 MetaCure – Tantalus 

87 IntraPace – Abiliti 

87 Leptos Biomedical – IPG 

88 Sentinel Group – Full Sense 

88 StimPulse 


8 

88 NeuroSigma 

88 Balloons and Space-Filling Surgical Products 

88 Allergan – Orbera 

89 Helioscopie – Heliosphere 

89 Spatz FGIA – Adjustable Balloon System 

90 ReShape Medical – ReShape Balloon 

90 Fulfillium 

90 Other Space-Filling Products 

90 Tulip Medical 

90 BaroSense – TERIS 

90 Gelesis 

91 Sleeve Gastrectomy – An Old Procedure Revived 

91 Lifestyle Medicine 

92 New Markets Opening for Existing Products 

92 Diabetes Control Is Another New Market 

93 Body Composition Analyzers 

93 Bruker Optics 

93 Cosmed 

93 Echo Medical Systems 

93 Hologic 

94 ImpediMed 

94 Jawon Medical 

94 Korr Medical Technologies 

94 Life Measurement 

94 Tanita 

94 Bodystat 

94 Metabolic and Other Testing Equipment 

94 ActiGraph 

94 Cosmed 

94 Korr Medical Technologies 

94 Microlife USA 

94 Mini Mitter 

94 Sable Systems 

95 Seahorse Bioscience 

95 Zen-Bio 

95 Behavior Modification for Weight Control 

95 BodyMedia – SenseWear 

95 GE Healthcare Lunar 

96 Aipermon 

96 iWhisper 

96 MEND Central 

96 Assisting Weight-Loss Efforts 

96 Aestis 


97 Movea 

97 Novartis Medical Nutrition 

97 Phoenix Care 

97 Suzuken 

97 Obesity-Related Diagnostics 

97 Interleukin Genetics 

98 Quantomix 

98 Other Obesity Diagnostics 

99 Science Highlights: 

Recent Research Breakthroughs in the Battle of the Bulge 

99 Fat-Fighting Enzyme Can Play Havoc with Cancer Cells 

99 For Bone, Appetite Regulators, It's Location, Location, Location 

100 Insulin, Body Temp Related 

100 Study Shows Fat Around Heart Decreases Heart Functions 

100 Starting Weight a Factor in Bypass Surgery 

100 New Obesity Target Involves Use of a 'Molecular Shunt' 

101 Studies: Links Among Obesity, Inflammation, Insulin Resistance 

102 New Factor for Converting Cells to 'Good' Brown Fat Identified 

102 Targets Are Identified for Battle of the Bulge 

103 In Feeding, Metabolism, It's All About Location 

104 Hypothalamic Overeating Gene Pegged 

104 Systems Biology Approach Finds Novel Obesity Genes 

105 Peripheral Endocannabinoids Linked to Fatty Liver Disease 

106 New Research Implicates Lipid Metabolites in Insulin Resistance 

106 $50M Sequence Project to Map Genomes in 1,000 People 

107 Study Relates Gastric Surgery to Diabetes 

109 Obesity Data 

125 Index 


10 

LIST OF TABLES 

13 Introduction and Analysis 

14 Cost of Lost Productivity Related to Overweight and Obesity 

14 Cost of Overweight and Obesity 

15 Costs Related to Overweight and Obesity, by Disease 

17 Annual Soft Drink Production in the U.S. 

18 Defining Overweight and Obesity for Adults 

18 U.S. Obesity Prevalence by Age, Race/Ethnicity and Sex, 2005-2006 

19 Overweight and Obese, by Age, U.S., 1971-2006 

20 Classification of Obesity and Risks of Co-Morbidities 

20 U.S. Obesity Prevalence by Age and Sex, 2005-2006 

20 Percentage of Disease Cases Related to Obesity 

21 Health Consequences of Obesity 

21 Obesity Is Linked to a Significant Increase in Chronic Conditions 

22 Obese Individuals Spend More on Health Care Than Smokers and Drinkers 

23 Contextual Influences on the Development of Childhood Obesity 

24 Global Hunger Statistics 

25 Percentage of Total Population That Is Obese, by Country 

26 Most Undernourished Countries, by Percent of Population Undernourished 

27 Percentage of Overweight Women in Developing Countries, Compared to U.S. 

27 The Inverted U of Wealth and Obesity 

28 Defining Obesity 

28 Health Insurance Coverage, U.S., Under 65 Years Old, 1984-2006 

33 Obesity Drugs: Big Opportunities for a Growing Problem 

33 Obesity Rankings by State 

33 Body Mass Index of U.S. Population 

33 Aggregate Medical Spending Attributable to Overweight and Obesity 

34 Estimated Adult Obesity-Attributable Percentages and Expenditures by State 

35 Rising Costs of Obesity 

35 Medications That Promote Weight Loss 

36 Percentage of U.S. Adults Who Are Overweight or Obese 

36 Percentage of U.S. Adults Who Are Obese 

36 Percentage of U.S. Adults Who Are at a Healthy Weight 

37 Company Survey Asking, 'What Aspects of Obesity Do Your Discovery Research 

and Drug Candidates Address?’ 

39 Obesity Drugs in Development 

41 Market for Prescription Obesity Drugs, 2007-2017 

45 Percentage of Patients with Obstructive Sleep Apnea 

65 Unfortunately, It's a Growth Market: 


65 Device and Drug Sales and Projection in the Clinical Management of Obesity, 

2004-2015 


66 Balance of Drug/Device Sales in the Clinical Management of Obesity, 2004-2015 

66 Bariatric Surgical Devices and Pharmaceuticals in Obesity, Worldwide Sales and 

Projection, 2006-2015 

67 Cost Effectiveness of Bariatric Surgery 

68 Responses from Family Practitioners Regarding Obesity Surgery 

68 Teen Surgeries for Obesity Are Increasing: Number of Bariatric Procedures for 

U.S. Teenagers 

69 Top Reasons Patients Don't Have Bariatric Surgery 

69 Number of Bariatric Surgeries in the U.S., 1993-2008 

69 Relationship Between Body Mass Index and Risk of Type II Diabetes Mellitus 

71 Products for Endoluminal Pouch Reduction 

77 Invasiveness of Roux-en-Y Gastric Bypass vs. Laproscopic Adjustable Gastric Banding 

84 Neuromodulation Products and Companies 

89 Space-Filling Products to Treat Obesity 

91 Ideal Bariatric Procedure Attributes 

92 Endoluminal Products for Weight Loss and Diabetes Control 

93 Companies with Interventional Therapies for Obesity and Diabetes in Development 

109 Obesity Data 

109 Personal Health Expenditures, by Source of Funds and Type, U.S. 2006 

109 Obesity as a Function of Income and Education 

110 Insulin Sensitivity Improves with Weight Loss in Patients with Type II Diabetes 

110 Strength of Evidence on Lifestyle Factors and Risk of Developing Type II Diabetes 

111 Strength of Evidence on Lifestyle Factors and the Risk of Developing Cancer 

111 Strength of Evidence on Lifestyle Factors and Risk of Developing Cardiovascular 

Diseases 

112 CDC's Recommended Community Strategies to Prevent Obesity in the U.S. 

114 Percentage of Obese Subjects Reporting Depression 

114 Percentage of People Who Are Depressed, by Relative Body Weight 

114 Relation Between Obesity and Depression 

115 Is Obesity an Epidemic in the U.S.? 

115 Higher Health Care Costs for Businesses 

116 What’s Behind the Obesity Epidemic? 

117 Health Care Costs of Obesity 

118 Obesity’s Impact on Health 

120 Global Hunger and Food Statistics 

120 Countries That Received the Most U.S. Foreign Aid in 2008 

121 Number of Undernourished People in the World, 1969/71-2009 

121 Global and Regional per Capita Food Consumption 

121 Undernourishment in 2009, by Region 

122 Obesity Deals and Data 

124 Total and Older Population, U.S.: 1950-2050 


12 

ACKNOWLEDGEMENTS 

The BioWorld ® and Medical Device Daily 

Obesity Report: Tipping the Market Scales with Biotech & Med-Tech 

Regimens was developed from a variety of sources: material taken from AHC Media’s group of publications, 

including BioWorld Today, BioWorld International, BioWorld Insight, Medical Device Daily, BioWorld Industry 

Snapshots, BioScan: The Worldwide Biotech Industry Reporting Service, interviews with industry experts in the 

biotech sector, company statements and websites, and analyst reports. 

We especially want to thank a group of writers from whom we have drawn material, either wholly or in part, 

excerpted or paraphrased: Glen Harris, BioWorld Today managing editor; Jennifer Boggs, BioWorld Today assistant 

managing editor; Holland Johnson, Medical Device Daily managing editor; Randy Osborne, BioWorld 

Insight editor; Anette Breindl, BioWorld Today science editor; Catherine Hollingsworth and Trista Morrison, 

BioWorld Today staff writers; Omar Ford and Amanda Pedersen, Medical Device Daily staff writers; John Brosky, 

Medical Device Daily European editor; Karen Pihl-Carey, BioWorld database editor; James Etheridge, Sharon 

Kingman, Nuala Moran and Cormac Sheridan, BioWorld International correspondents; and Jeffrey Berg, Larry 

Haimovitch, Kathleen Kite-Powell and Diana Tucker, Medical Device Daily contributing writers. 


— Michael Harris, Executive Editor 

— Amanda Lyle, Managing Editor 

March 2010

An Abstract Analysis: 

Obesity Treatment and Trends, Today and Tomorrow 

Atlas Shrugged . . . and Slumped 

Under the Weight of Global 

Obesity 

The world is big and getting bigger in 

terms of weight, while the drug and 

medical technology markets that society 

has become reliant on to develop 

products for all the major illnesses that 

afflict it are trying to play catch-up and 

cope with a half-century of weight 

gain that threatens to clog society’s 

major veins of productivity and commerce, 

along with its health. 

The weight management market, 

depending on which products, procedures 

or services are included, is valued 

in a range of $1.4 billion, which 

represents the current drug market, to 

$550 billion, which comprises the 

“kitchen sink” market, in which everything 

(from partial stomach excision to 

hypnotism to diet soda) that purports 

to address weight issues is included. 

Unfortunately, biopharma drugs 

account for a lackluster less-than-1 

percent of the total market. Medtech’s 

contribution is better and 

increasing, but still in the same basement 

category of the overall obesity 

market. 

Med-tech and pharma dominate the 

medically prescribed treatment market 

for obesity now, although pharma’s 

stint at the top is more by default than 

a solid R&D aptitude on its part. 

Medical technology products and services 

are very effective in treating obesity, 

but its procedures often are regarded 

as “for extreme use only” and perceived 

to be inappropriate for many 

who likely would opt for an effective 

drug regimen over a more risky, albeit 

reliably effective, surgery. 

Approximately 80 percent of the hospitals 

surveyed for a study that was 

published in The Journal of the 

American Medical Association in 

January 2008 on the prevalence of 

obesity reported an increase in admissions 

of severely obese patients, 

reflecting a 22 percent increase from 

the previous year. Approximately half 

of those hospitals reported that they 

purchased new categories of supplies 

for the treatment of obese patients, 

including beds, lifts and wheelchairs. 

At the moment, surgery is more effective 

in treating obesity than prescribed 

pharma drugs, and it has nothing to 

do with the difference in the number 

of drug products vs. the number of 

services and devices. While use of 

approved pharmaceuticals can reduce 

excess weight by 5 percent to 10 percent, 

patients undergoing obesity surgery 

lose 50 percent to 90 percent of 

their excess weight. 

Pharma’s less-than-blockbuster market 

run is helped by the absence of 

approved biotech products, but 

biotech looms to exploit the gaping 

hole in the treatment market, perhaps 

as early as late-2010. Whenever the 

leading crop of biotech applicants 

gains approval, they are immediately 

expected to find revenue success, 

manifesting the market’s long-starved 

appetite and wholesale readiness for 

safer, more efficacious, easy-to-administer 

therapeutics. 

Although med-tech research advances 

are hinting at the possibility of some 

innovative standalone and combination 

products that could enter the market 

within the next five years, the advantage 

of biotech products would seem 

to be the hope of manipulating cellular 

activity and “turning off” obesity triggers. 

Based on encouraging recent 

results from med-tech, such as the 

announcement in March 2010 that a 

team of California Institute of 

Technology researchers had successfully 

delivered cancer-fighting RNAi therapies 

to particular parts of the body via 

nanotech polymer robots, such 

ANALYSIS 

advances in gene therapy could break 

down that technology’s biggest barrier 

to success – patient site delivery of medication 

– and hasten the development of 

many stalled therapeutics in the clinic. 

Such potential offers a respite from the 

inefficacy/side effect dilemma that 

beleaguers pharma drugs on the market 

as well as in the clinic, as well as the 

“drastic treatment” perception that frequently 

designates medical technology 

procedures and devices. “Drastic 

gastric” bariatric surgeries, temporary 

weight loss prescription drug results 

and OTC weight loss pills that all but 

come with an FDA recommendation to 

carry an extra set of pants, leave skepticism 

in patients and the door open for 

the biotechnology industry to ride in on 

a white horse with that magic pill solution 

that brings a higher and longerterm 

efficacy rate, reduces the need for 

surgeries and carries less ominous side 

effects than excessive flatulence and 

irrepressible diarrhea. 

There are currently no approved 

biotech drugs in the space, but they 

loom, as do the revolutionary medical 

technologies that may overcome the 

delivery mechanism challenges that 

have thwarted advances in administering 

gene therapy biotech drugs to 

locations within the body. 

There are currently 38 drugs in clinical 

trials for direct obesity applications, 

with 19 in late stage trials and three 

filed for approval. That is not an 

impressive number, considering the 

hundreds of clinical trials being conducted 

for pervasive diseases such as 

cancer and heart disease; however, it 

is an indication that the drug development 

industry is not ignoring the 

unmet need. Twenty years ago, there 

was no serious or comparable clinical 

effort to address the growing indication. 

That had at least something to 

do with the perception that being 


14 

overweight or obese was commonly 

regarded as a problem of personal 

overindulgence that could be sufficiently 

addressed by personal changes 

in habit. 

This view was reflected by the increase 

in markets for personal exercise equipment, 

health club membership enrollment, 

diet food/beverages and other 

products relative to shedding weight. 

However, markets that treated obesity 

as a medical problem were still largely 

unaware of or uninterested in the 

problem of obesity, and that decision 

has created a wide gap between obesity 

prevalence and a widely preferred 

and applied obesity treatment that 

offers a softer perception of its application 

than bariatric surgery, the current 

leading treatment option. 

As illogical as it may seem, this problem 

(just like the weight often does on 

individuals) crept up on everyone, 

even though it unfolded right before 

our eyes. The opportunity to control 

the proliferation of obesity is still upon 

those industries, but its 50-year head 

start has given med-tech and biotech 

companies that deem to control its 

further spread an arduous, but far 

from impossible, task. 

Obesity Can’t Be Cured, Resolved 

or Wished Away by Re-defining it 

It would be great if the current debate 

regarding the assignation of obesity as 

a disease, condition, factor, symptom 

or non-issue was actually more meaningful 

in combating its increasing 

prevalence. Unfortunately, the inability 

to define the world’s growing problem 

with increasing body weight does little, 

if anything, to disrupt the trend 

itself. No matter how it is defined, it is 

a big fat problem and a runaway juggernaut 

affliction that could reverse 

the increasing average lifespan trend 

that has characterized the U.S. population 

over the past 200 years. 

Unfortunately, classifying obesity is 

irrelevant compared to controlling it. 


Whether or not the diet industry and 

the medical treatment community are 

hyping the situation to drum up business 

has no bearing on the literal pervasiveness 

of obesity. Obesity is dangerous 

and it is crippling society in the 

workplace, the marketplace and on 

personal levels, inasmuch as we know 

it annually causes millions of hours of 

lost productivity; it drains billions in 

currency from the global economy in 

health care-related costs; and it directly 

causes or contributes to the deaths 

or infirmity of millions. At the least, it 

contributes to the most insidious diseases 

on Earth and impairs the lives of 

an immeasurable number of people. 

So it doesn’t matter whether we call it 

the word’s fastest-growing disease or 

the world’s most overhyped condition. 

New medical and therapeutic technologies 

are needed to fill the increasing 

gap between the world’s weight 

gain and the relatively lean combined 

response of the weight control, health 

and fitness, and prescription treatment 

market. 

That said, the classification of obesity 

does bear importance since officially 

regarding it as a disease is likely to 

increase public awareness, draw more 

government resources and initiate relative 

anti-obesity agendas. The prevalence 

of obesity has been increasing 

for over a century and has increased 

substantially in the past several 

decades. 

Clear and consistent evidence shows 

that obesity increases the risk of many 

morbidities and reduces both the quality 

and the quantity of life. The decision 

by the U.S. government’s Health 

and Human Services agency to regard 

it as a disease and cover it so extensively 

should have ended the debate. 

Exercise more, eat less. That is the 

application for weight control in its 

simplest form. Unless you are genetically 

predisposed to being overweight, 

those words of advice should be 

Cost of Lost Productivity 

Related to Overweight 

and Obesity 

Workdays lost: $39.3 million 

Physician office visits: $62.7 million 

Restricted-activity days: $239 million 

Bed-days: $89.5 million 

Source: Weight-control Information 

Network. 

Cost of Overweight and 

Obesity 

Total Cost: $117 billion 

Direct Cost: $61 billion 

Indirect Cost: $56 billion 

Source: Weight-control Information 

Network. 

enough to keep the “World According 

to BMI” in physically fit frames. But in 

the real world, the battle of the bulge 

is a lifelong fight. In the case of most 

of the U.S. population and approximately 

a quarter of the global populace, 

the battle is already a statistical 

defeat for humankind. To add insult 

to injury, future generations already 

are predestined to explode this market 

into more record echelons of 

prevalence. 

The only thing we seem to agree on is, 

for some reason, the U.S. population 

started gaining weight in the 1960s. 

We presume to attribute it to the TV 

dinner/drive-through/microwave 

lifestyle that fascinated the citizenry by 

saving time in the kitchen and allowing 

us to devote more time worshipping at 

the feet of the dubious harbinger of 

the sedentary life – the television. 

Fast-forward to the twenty-first century, 

in which processed foods, smart 

devices and leisure-time gadgets constantly 

emphasize the importance of 

saving time above all else. That 

undoubtedly has contributed to create 

a culture that can encourage obesity, 

but that may be a theory with holes.

More people are exercising, dieting 

and committing to an overall healthier 

lifestyle than at any previous time in 

the history of the U.S., as evidenced by 

the $100-plus billion weight-control 

and physical fitness market. However, 

three times as many people are gaining 

weight in 2010 compared to the 

citizenry of the 1950s, even as each 

generation has become more weightconscious, 

but less able to do much 

about it. 

As most people who have exercised or 

dieted have discovered, losing weight 

is difficult to begin with, but is even 

further exacerbated by trying to sustain 

the weight loss for a lifetime. 

Costs Related to Overweight and Obesity, by Disease 

dollars in US millions 

100,000 

90,000 

80,000 

70,000 

60,000 

50,000 

40,000 

30,000 

20,000 

10,000 

0 

2,900 

breast cancer 

933 

endometrial cancer 

3,500 

colon cancer 

21,200 

osteoarthritis 

hypertension 

gallbladder disease 

98,000 

24,000 

4,100 3,400 3,900 

Type II diabetes 

costs of physical inactivity 

lost productivity costs 

Source: NutriStrategy, citing the American Heart Association, National Institute of 

Diabetes and Digestive and Kidney Diseases, and U.S. Department of Health and 

Human Services. 

Exercising or adopting a more nutritional 

regime does not guarantee permanent 

weight loss, as life’s bumpy 

road offers plenty of opportunities to 

“fall off the wagon.” Many have 

dropped out of the overweight category, 

only to find themselves back 

where they started from – or worse. 

BioWorld estimates that more than 55 

percent of significantly successful 

dieters (those who lose 30 pounds or 

more) put the lost pounds back on 

within one year, and 88 percent regain 

the weight within five years. This trend 

commonly leads to either dangerous 

yo-yo dieting, in which weight is 

repeatedly lost and regained, or the 

equally unhealthy tendency to abandon 

one’s weight loss objectives, 

which often results in weight gain in 

excess of the patient’s starting weight 

at the beginning of the dieting 

process. 

These situations portend the opportunity 

for government-approved medical 

and therapeutic procedures, devices 

and products that can compete with 

the market preponderance of risky, 

holistic “quick-fix” and drastic products 

and technologies that are bringing 

in more revenue to producers than 

apparent benefit to consumers and 

patients. 

Drugs and Devices in the Obesity’s 

Market’s Growing Future 

There is particularly room for growth 

in the drug sector of the obesity market 

to exploit the revenue and treatment 

opportunity, as the combined 

percentage of the pharmaceutical and 

biotechnology markets’ contribution is 

1 percent of the overall obesity treatment 

market. The drug market, led by 

the contribution of a handful of pharmaceutical 

drugs collectively worth 

barely the value of one typical blockbuster 

drug, resides at the bottom of 

an overall lucrative weight management 

market, and is uncharacteristically 

lagging in relation to its position 

in other fields of health care treat- 


16 

ment. Meanwhile, the med-tech 

industry is exploiting the lack of 

approved drugs to quadruple its 

growth rate for its most popular products 

and services. 

Given the public’s obsession with 

weight control and other dynamics 

including the lack of a widely prescribed 

drug and the success of “last 

resort” invasive surgical procedures, 

the leading drug candidates, once 

given the safety and efficacy approval 

of bodies, particularly the FDA and 

European Medicines Agency (EMEA), 

stand to become the next class of 

blockbuster drugs, as soon as in their 

second post-approval years. 

Historically, the consumer market has 

aggressively pounced upon anything 

available that hints at being “lose 

weight fast”-effective and the substantial 

patient market seeking to shed 75 

pounds or more is embracing the most 

extreme option available (surgical procedures) 

to shed pounds. So, a market 

entry by any of the biotech drugs vying 

to become the first on the market in the 

obesity space is projected to be wellreceived 

by physicians and patients 

looking for an efficacious middleground 

between hyperbole and surgery. 

Medical technology will be cannibalized 

by the entry of new biotech 

drugs, particularly in applications 

involving moderate weight loss, but 

the overall market will continue to 

grow, as the future severely to morbidly 

obese class is already in place, led by 

a follow-on generational class of 

genetically predisposed offspring and 

those who already have fallen victim 

to the sedentary life. Possibly, it will 

take the lifestyle-changing efforts of 

another generation to “devolve” from 

the curse of genetic markers that have 

doomed them to becoming overweight 

and denounce the habits of 

the chronically overweight. 

The general philosophy among 

patients to try drugs before scalpels 


will result in a slowing of growth, but 

not a reversal, in the bariatric surgery 

market, as the severely obese patient 

group still will remain securely reliant 

on the surgery sector for its most 

viable option in fighting morbid obesity 

with the quickest results. Although 

patients want the magic pill solution, 

they still want results fast and the 

bariatric surgeries, as well as certain 

other procedures, offer unparalleled 

(excluding rare cases of exceptional 

patient willpower) reliable weight loss 

in the most extreme cases. 

The anti-obesity drug market is trying 

to become an integral component of 

the $650 billion global weight management 

market that literally has the 

weight of the world on its shoulders as 

it strives to manage the world’s diet 

and health. This massive market is 

comprised of many sectors, including 

diet food providers, health care services, 

lifestyle therapies, fitness services 

and equipment, and even the selfhelp 

industry, but none is looked to 

with more confidence to produce the 

magic bullet cure as the med-tech and 

(more particularly) drug development 

industries. 

Med-tech applications are currently 

leading the on-the-market products 

race to accommodate patients with 

viable innovations for weight loss, but 

given the fact that many patients and 

payers view its technologies as invasive, 

radical and, often, uninsurable, 

the door is still open for immediate 

and substantial growth for potential 

clinical therapeutic candidates that 

have the opportunity to get approved 

during the current obesity onslaught 

that is outpacing all attempts to curb 

its growth. 

Associative costs that arise due to obesity’s 

effect on chronic diseases such as 

diabetes and heart disease, as well as 

obesity’s impact on devices, medications 

and procedures such as wheelchairs, 

arthritis drugs, body part 

replacement surgeries, and portable 

oxygen tanks for asthmatics – to name 

a few – can only be estimated, but 

could arguably push the total value of 

the market to the $1 trillion threshold. 

When biotech drugs enter the market, 

they are almost assured a considerable 

and immediate slice of the sector. Even 

with the vast amount of OTC medications, 

med-tech options, fitness outlets, 

diet foods and services, and even 

psychological alternative therapy regimens 

that are available, there is no 

leading course of therapy that has 

won the confidence of the public or 

taken on the standard-bearer mantle 

as the go-to face of the industry. One 

billion-dollar drug could do that within 

two years after approval. 

A good omen for the potential of 

biotech drugs is that the public and 

insurers would overwhelming, perhaps 

absolutely, prefer a therapeutic drug 

regimen over a surgical one. Drugs 

would be even more desired as a 

course of treatment over the litany of 

devices that facilitate a patient’s mobility 

or body functions that have been 

impaired or destroyed due to the burden 

of obesity on the body. 

But biotech is no longer the smartest 

one in the room, as medical technology 

has maintained the lead in providing 

the go-to solutions for the bulk of 

obesity patient applications. The leading 

technology that has put biotech in 

the back seat has been the increasing 

use of bariatric surgeries. Additionally, 

there are many devices that address 

the symptoms of not only obesity, but 

diseases such as diabetes and heart 

disease that wind up requiring replacement 

body parts or apparatus that 

mimic, or assist, body functions. 

Examples include heart valves, diabetes 

pumps and even wheelchairs. 

Medical technology products and procedures 

such as bariatric surgery and 

prosthetics that are applied as a result 

of direct obesity or its responsibility in 

contracting other diseases may be the

least desired, but most beneficial solution 

to addressing the most severe 

cases of obesity at this time. The applications 

it offers are invasive or may be 

disconcerting reminders of a patient’s 

condition, but they are regarded to be 

effective in reversing the most severe 

cases of the disease and compensating 

for the ravages of the condition. 

Medical technology is the premiere 

option in treatment of obesity, indicating 

the gap between med-tech solutions 

and any imminent emergence of a 

widely prescribed biologic therapeutic. 

And finally, let’s face it . . . if there was 

a product to manage obesity that had 

the public confidence and therapeutic 

efficacy to rule the market, we would 

know about. This anti-obesity market 

rakes in revenue from a pattern of 

fragmented applications that rely on 

appealing to, and exploiting, a variety 

of patient triggers ranging from gullibility 

to desperation. Once a new class 

of drugs gets the blessing of the FDA, 

the sky is the economic limit for its 

bottom line. 

Perhaps it’s not the products that will 

lead to success, but the failure of the 

patients themselves to follow through 

and maintain the regimen, since 

willpower seems to be in short inventory 

in the weight loss game. After all, 

bariatric surgeries are successful, but 

are not accountable for weight regain 

once the device is removed or the procedure 

is ended. Manufacturers of 

OTC diet pills and gadgets have 

become assiduous in circumventing 

government scrutiny by stating associated 

regimes for the patients to follow 

to help facilitate their products’ claims. 

In a nutshell, it’s usually some variation 

of “eat right, exercise, discard 

unhealthy lifestyle habits,” putting the 

onus for failure on the patient, inasmuch 

as everyone knows that if you 

do those things, you don’t even need 

any help maintaining a healthy weight 

in the first place. Never has a market 

made so much money from producing 

so few real results. 

Finding a magic pill to cure our overweight 

problem now rivals the popularity 

of humankind’s desire to find a 

Fountain of Youth. We not only want 

to live forever, we want to be lean in 

our immortality. 

More than likely, the future will belong 

to biotechnology, as there are clinical 

trials that portend pipeline success 

coming as early as mid-decade; however, 

med-tech’s run atop the list of 

most-used treatments is secure in its 

profitable run for the time being. 

The Overweight Population . . . 

Epidemic, Risk Factor or 

Misdiagnosis? 

Society, including the health care and 

life sciences industries, does not yet 

know how to officially or unanimously 

classify obesity into a proper category, 

even as it has developed right before 

our eyes into the fastest-growing 

scourge in the world over the past 50 

years. 

Maybe that should shed some insight 

on why we didn’t collectively see it 

coming and cutting a swath of pervasiveness 

that is likely to encumber at 

least three generations in the next 25 

years. That 25-year prognosis of widespread 

affliction is based on the successful 

development and approval of 

drugs or medical products and services 

that would put the obesity epidemic 

into remission – a scenario that is still 

hypothetical at this time. The scenario 

that is projected to unfold without the 

intervention of a magic pill or procedure 

or device is a world in which the 

majority of the population is overweight 

or obese, putting a never-seenbefore 

burden on almost every functional 

and core aspect that maintains 

the equilibrium and evolvement of 

society. 

Such doomsday maxims may be what 

incite critics in the “Not-A-Disease” 

camp, but the underlying facts on the 

prevalence, impact and prospects of 

obesity are empirical: It’s bad and 

deserves the attention necessary to 

curtail it. Obesity is not a condemnation 

that one is fat; it is a diagnosis 

that one is sick. It is a big problem that 

is created the need for a corresponding 

course-of-therapy market. It’s not 

a virus. It is not contagious. It is a manmade 

disease. We don’t know who 

Annual Soft Drink Production in the U.S. (12 ounce 

cans/person) 

700 

600 

500 

400 

300 

200 

100 

0 

Diet soda 

Regular soda 

1947 1957 1967 1977 1987 1997 1998 2000 2004 

Source: U.S. Department of Agriculture Research Service (1947-1987); Beverage 

Digest (1997-2004). 


18 

the first obese human was, but 

although the disease can be genetically 

passed on now, the first person to 

get the disease probably ate his way 

into it. 

Even as obesity is currently impacting 

society in many unpleasant ways, there 

is still debate over whether it is a disease, 

risk factor, epidemic, symptom, 

condition, affliction, addiction, mental 

illness or something that is not even 

necessarily unhealthy. We cannot even 

decide on its origins. Is it possible for a 

disease to originate from the first television 

set, microwaves, TV dinners, soft 

drinks, mass production of the automobile, 

the drive-thru and the end of 

the Last-Meaningful-Thing-That-Kept- 

Us-Fit/Focused: World War II? Did 

those dynamics blaze the path for 

what some people regard as the modern 

crop of obesity onset triggers such 

as genetic predisposition, food addic- 


tion, depression, smart devices, stress 

and the Never-Ending-Day lifestyle? 

As a disease, obesity directly afflicts 

the health of billions of people. As a 

risk factor for the world’s most deadly 

diseases, it contributes to the mortality 

of an unbounded number of people. 

However one decides to categorize 

it, obesity is the leading candidate 

to be the next great health threat. 

Yet, the therapeutic and med-tech 

treatment market is losing ground to 

Defining Overweight and Obesity for Adults 

obesity’s prevalence. The wholesale 

curative and facilitative response of 

those two markets, among the world’s 

most innovative, may eventually trump 

obesity’s rampant tantrum that is running 

amok on the economy and compromising 

the public’s well-being. 

However, obesity, at the moment, is 

legitimately an unmet need treatment 

market that is growing bigger while we 

continue to wait for the authoritative, 

market-leading therapy or technology 

that will characterize the anti-obesity 

treatment market in the future. 

Height Weight Range BMI Considered 

5’ 9” 124 lbs or less Below 18.5 Underweight 

125 lbs to 168 lbs 18.5 to 24.9 Healthy weight 

169 lbs to 202 lbs 25.0 to 29.9 Overweight 

203 lbs or more 30 or higher Obese 

Source: Centers for Disease Control and Prevention. 

U.S. Obesity Prevalence by Age, Race/Ethnicity and Sex, 2005-2006 

percent 

70 

60 

50 

40 

30 

20 

10 

0 

20-39 40-59 60+ 20-39 40-59 

Men 

Age in years 

Women 

Source: Centers for Disease Control and Prevention and the National Center for Health Statistics. 

60+ 

White 

Black 

Mexican- 

American

In July 2004, the U.S. Department of 

Health and Human Services eliminated 

the long-standing statement from the 

Medicare Coverage Issues Manual that 

obesity was not a disease. Until 

February 2006, gastric bypass surgery 

was the only weight-loss surgical procedure 

that was covered by Medicare, 

but now, other surgical procedures 

such as laparoscopic adjustable gastric 

banding and laparoscopic biliopancreatic 

diversions are covered by the 

agency. These actions led to more coverage 

from private health insurers as 

well and have been a revenue booster 

for the bariatric surgery market and 

one of the government’s biggest coverage 

applications. 

Based on the designation of many of 

the world’s prominent health organizations, 

it is defensible to say obesity is 

the world’s most prevalent disease, the 

biggest disease risk factor and the 

most underserved disease treatment 

market. Normally, that would qualify 

any health condition for epidemic status. 

This market is too big and ominous 

to remain an unmet need market, or 

even a market in which therapeutic 

and medical solutions cannot be reliably 

projected to contain the prevalence 

rate within a 10-year period. That 

is the classic recipe for epidemic. 

Based on widely regarded criterion 

attributable to, or acknowledged by, 

the World Health Organization (WHO), 

Centers for Disease Control and 

Prevention (CDC), National Institutes 

of Health (NIH), FDA and literally every 

other organization that studies or regulates 

population health issues, more 

than 65 percent of the people in the 

U.S. are obese, while globally, 40 percent 

classify as overweight and obese. 

An approximate 1.2 billion … that is 

the global market of the twenty-first 

century today, in which obesity, as of 

2010, incongruously rivals world 

hunger as the most ubiquitous threat 

to good health, while surpassing 

tobacco as the most predominant 

cause of preventable death in the U.S. 

Overweight and Obese, by Age, U.S., 1971-2006 

percent 

percent 

percent 

80 

70 

60 

50 

40 

30 

20 

10 

0 

40 

35 

30 

25 

20 

15 

10 

5 

0 

50 

40 

30 

20 

10 

45-64 years 

18-29 years 

30-44 years 

Overweight including obese 

1971 1976 1981 1986 1991 1996 2001 2006 

Overweight but not obese 

1971 1976 1981 1986 1991 1996 2001 2006 

Obese 

0 

1971 1976 1981 1986 1991 1996 2001 2006 

Source: CDC/NCHS and BioWorld estimates. 


20 

Classification of Obesity and Risks of Co-Morbidities 

WHO Popular BMI Risk of 

Classification Description (kg/m2) Co-Morbidities 

Underweight Thin 25.0 

Pre-obese Overweight 25 - 29.9 Increased 

Obese Class I Obese 30.0 - 34.9 Moderate 

Obese Class II Obese 35.0 - 39.9 Severe 

Obese Class III Morbidly Obese > 40.0 Very severe 

Source: World Health Organization. 

percent 

U.S. Obesity Prevalence by Age and Sex, 2005-2006 

50 

40 

30 

20 

10 

0 


Men 

Women 

Total 20-39 40-59 

Age in years 

60+ 

Source: Centers for Disease Control and Prevention and the National Center for 

Health Statistics. 

percent 

Percentage of Disease Cases Related to Obesity 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 

Type II diabetes Cardiovascular 

disease 

Note: *Diagnosed among obese individuals 

Source: Wellness International Network Ltd. 

Breast and 

colon cancer* 

Gall bladder 

surgery 

High blood 

pressure 

As such, the obesity market represents 

the next great health epidemic. In the 

U.S. the majority of American adults 

comprise the obesity market, while 40 

percent of adults in the UK are in that 

class. Globally, 1.2 billion adults are 

overweight and more than 400 million 

are obese, putting 25 percent of the 

world’s population in the disease’s 

grasp, with those figures projected to 

respectively increase by mid-decade to 

2.3 billion and 700 million, creating 

the need for a huge treatment market 

that is currently emerging at an everso-deliberate 

pace. 

Adult obesity rates in the U.S. have 

tripled since 1960, while childhood 

obesity rates have tripled since 1980, 

according to data from the CDC. 

Obesity is a disease with tentacles. 

Aside from its own malicious effects, it 

directly causes or contributes to more 

than 100 other niggling-to-mortal 

afflictions and diseases. Obesity is 

proven to be a risk factor in the development 

of diseases such as Type II diabetes, 

heart disease and certain types 

of cancer. There is research that indicates 

its connection to mental illnesses 

such as depression and Alzheimer’s 

disease. Additionally, there are debatable 

issues regarding the additive 

aspect of being overweight. The chief 

argument centers on whether addiction 

to food or improper eating habits 

causes obesity or if a genetic predisposition 

for obesity or our human 

response to external factors trigger the 

compulsive craving for food. 

The sheer numbers that distinguish its 

prevalence qualify obesity for epidemic 

status, especially since an epidemic does 

not have to involve a disease. It is widespread 

and growing and, it is observably 

affecting the health of millions in a negative 

way. The contraction of obesity 

and overweight status is hereditary and 

behavioral. It is not contagious, but it is 

growing faster than even the common 

cold, the world’s most pervasive communicable 

affliction.

Health Consequences of Obesity 

Research shows that as weight increases to reach the levels referred to as overweight 

and obesity, the risks for the following conditions also increases: 

Coronary heart disease 

Type II diabetes 

Cancers (endometrial, breast and colon) 

Hypertension 

Dyslipidemia 

Stroke 

Liver and gallbladder disease 

Sleep apnea and respiratory problems 

Osteoarthritis 

Gynecological problems (abnormal menses, infertility) 


Obesity Is Linked to a Significant Increase in Chronic 

Conditions 

increase in chronic conditions (percent) 

70 

60 

50 

40 

30 

20 

10 

0 

obese 

aging from 30 to 50 

living in poverty 

current smoker 

heavy drinker 

past smoker 

Baseline = comparable normal-weight individuals with no history of smoking or 

heavy drinking. 

Source: RAND Corp. "The Health Risks of Obesity: Worse Than Smoking, Drinking, 

or Poverty." 

The ominous data on obesity’s trends 

raise rational concern regarding its 

impact on burdening the public’s 

health, overloading the health care 

system, short-circuiting the economy 

and disrupting the general evolution 

of society with its permeating reach 

that affects so many lives and aspects 

of daily living. 

Obesity now contributes to the prevalence 

of more than 30 diseases and 

accounts for more than 25 percent of 

all health care costs in the U.S., 

according to an annual report, F as in 

Fat: How Obesity Policies Are Failing in 

America 2009, published by Trust for 

America’s Health, a non-profit anti-disease 

advocacy organization, and the 

Robert Wood Johnson Foundation 

(RWJF), a health and health care advocacy 

organization. 

The report says adult obesity rates 

increased in 23 states and did not 

decrease in any state from July 2008 

through July 2009. Additionally, the 

percentage of obese or overweight 

children was 30 percent or higher in 

30 states. 

Another report focusing on the subject 

of determining whether or not 

obesity qualifies as a disease stopped 

short of directly answering the question, 

but gave a strong statement that 

insinuated the opinion that if it wasn’t 

an official disease, it was something 

just as bad – or worse. The white 

paper report, Obesity as a Disease: A 

White Paper on Evidence and 

Arguments, was commissioned by the 

Council of the Obesity Society, the 

leading professional anti-obesity advocacy 

society, to examine and report on 

the issue. A look at the findings of the 

white paper gives the impression that 

it sounds like a disease, conducts itself 

like a disease, but also carries unfavorable 

aspects that other major diseases 

don’t even have. Among its grim findings 

on the matter of obesity, the 

report says: “Our panel struggled with 

the complexity of the issues surround- 


ing the question; the members held a 

diversity of views, as did the field of 

obesity researchers. Nevertheless, the 

panel’s members wish to note that there 

was absolutely no disagreement on the 

following fundamental points . . . 

• Obesity is a complex condition with 

many causal contributors, including 

genetic ones and many environmental 

factors that are largely beyond individuals’ 

abilities to choose or control. 

• Obesity causes much suffering. 

• Obesity causally leads to many 

aspects of ill health, to functional 

impairment and reduced quality of 

life, to serious disease, and to greater 

mortality. 

• Successful treatment, although difficult 

to achieve, produces many benefits, 

including prevention of disease 

and reduced mortality rate. 

• Obese persons are subject to severe 

societal discrimination in ways that 

those with seemingly similar chronic 

conditions, such as hypertension, dyslipidemia, 

and diabetes, are not. For 

example, obese individuals are waited 

on more slowly by salespersons, less 

likely to be rented apartments, less 

likely to be offered jobs, even when as 

qualified as other applicants, and less 

likely to receive support for higher 

education from parents, and often are 

looked down on by educators and 

health professionals.” 

22 

Obesity Challenges Are Smoking 

for a Dubious Title 

Tobacco use has long been alone at 

the top of the list as the most insidious 

culprit to menace society with the 

consequences of its actions, but now 

the cancer whisperer has a boogeyman 

sidekick. 

Obesity also has the unpleasant distinction 

of being the first condition to 

rival smoking as the most preventable 

cause of death, according to the 

WHO. Usually, the cigarette comes 

after the meal, but they are served in 

tandem as a one-two gut punch for 

society. 


Obese Individuals Spend More on Health Care Than 

Smokers and Drinkers 

increase in costs (percent) 

120 

100 

80 

60 

40 

20 

0 

-20 

Services Medication 

In addition to being the leading cause 

of preventable death, obesity now also 

rivals smoking as the biggest preventable 

threat to human health, according 

to a new study. A Columbia University 

and City College of New York study 

released in January 2010 calculates the 

quality-adjusted life years (QALYs) that 

are lost as a result of obesity are now 

equal to, or exceed, the corresponding 

QALYs from tobacco use. 

QALYs provide a measurement of the 

health gain or loss associated with diseases, 

injuries or therapies, and the 

study points to a trend that saw the 

quantity of smokers decrease by 18.5 

percent between 1993 and 2008, while 

the proportion of obese people 

increased 85 percent during that time. 

The study said smoking caused more 

deaths, but obesity caused more illness. 

Across the pond, an Oxford University 

report published its findings that 

severe obesity is as hazardous to 

health as a lifetime of smoking, short- 

Obese 

Aging from 30 to 

50 

Current smoker 

Heavy drinker 

Past smoker 

Baseline = comparable normal-weight individuals with no history of smoking or 

heavy drinking. 

Source: RAND Corp. "The Health Risks of Obesity: Worse Than Smoking, Drinking, 

or Poverty." 

ening life by a decade for severe obesity 

and as much as three years for 

moderate obesity. The Oxford study is 

based on data from a million people 

worldwide and it estimates 25 percent 

of all deaths from heart attack and 

stroke, as well as one in 16 deaths 

from cancer, in the UK are attributable 

to being overweight and obese. 

Ironically, it is arguable that the a significant 

percentage of those who help 

themselves by stopping smoking also 

gain weight as a side effect, thus kicking 

one bad habit, but picking up 

another, now just as dangerous, to 

compensate. 

Childhood Obesity Is Dooming a 

Generation Before it Gets Started 

The diabetes epidemic is being fed by 

an obesity scourge that is proliferating 

in children and young adult populations 

that are increasingly becoming 

vulnerable to diseases that, until 

recently, typically afflicted middle-aged 

people.

School lunch 

programs 

Work 

demands 

Contextual Influences on the Development of Childhood Obesity 

Nutritional 

knowledge 

Ethnicity 

Foods available 

in the home 

Accessibility 

of recreational 

facilities 

Childhood obesity has more than 

tripled in the past 30 years. The prevalence 

of obesity among children ages 

six to 11 years increased from 6.5 percent 

in 1980 to 19.6 percent in 2008. 

The prevalence of obesity among adolescents 

aged 12 to 19 years increased 

from 5.0 percent to 18.1 percent. 

Obesity is the result of caloric imbalance 

(too few calories expended for the 

amount of calories consumed) and is 

mediated by genetic, behavioral and 

environmental factors. Childhood obesity 

has both immediate and long-term 

health impacts. The CDC estimates that 

in this decade, 50 percent of the population 

age 18 and under in the U.S. will 

be clinically overweight, if trend conditions 

continue at their current rate. 

The mitigating factor in this statistic is 

not fashion, body appearance or soci- 

Dietary 

intake 

Parents’ dietary 

intake 

COMMUNITY AND 

DEMOGRAPHIC 

FACTORS 

PARENTING STYLES AND 

FAMILY CHARACTERISTICS 

CHILD 

BEHAVIORS 

CHILDHOOD 

OBESITY 

Physical 

activity 

Encouragement 

of activity 

Accessibility of convenience 

foods and restaurants 

etal perception. It is a life-or-death 

health issue, as the associative 

amount of diseases, complications, 

mortality risks and economic drain on 

people and society continues to 

increase as a trend that could result in 

a predominantly obese world by midcentury. 

To further extend the disastrous 

forecast, the weight carried by 

the overweight majority class of children 

in this decade is likely to already 

have the genetic makeup in place to 

trigger a new generation of obesity in 

their as-yet-to-be-born children. If any 

industry is structured to address such 

issues as turning off, or otherwise reprogramming 

genetic markers that 

predetermine or initiate disease, it is 

the biotechnology industry. This presents 

the target, and opportunity, for a 

huge market foray for biotech companies 

involved in gene therapy R&D 

applications. 

Sedentary 

behaviors 

Socioeconomic 

status 

Parents’ 

weight status 

Parents’ activity 

patterns 

Monitoring 

TV hours 

Neighborhood 

safety 

School PE 

programs 

Source: Penn State College of Health & Human Development, citing Davison & Birch (2001). Obesity Reviews, 2, 159-171. 

A World Equally Hungry and 

Overfed 

For the first time in history, the number 

of people overweight and obese 

equals the number of people malnourished. 

While the world’s underfed 

population has declined slightly since 

1980 to 1.1 billion, the number of 

overweight people has surged to 1.1 

billion. 

Based on widely disseminated criterion 

issued by the WHO, CDC, National 

Institutes of Health and literally every 

other organization that studies population 

health issues, about 66 percent 

of the people in the U.S. are overweight 

or obese, while globally, 40 

percent is classified as fat. So, 1.2 billion 

people . . . that is the obesity market 

of the twenty-first century, in 

which global obesity incongruously 

rivals world hunger as the most ubiq- 


24 

Global Hunger Statistics 

% children % population Global hunger Global hunger 

underweight undernourished index - label index - value 

Middle East 

Iran 11 4 Low

Global Hunger Statistics, cont. 

% children % population Global hunger Global hunger 

underweight undernourished index - label index - value 

Lesotho 20 13 Serious 14.3 

Liberia 26 50 Extremely alarming 31.8 

Madagascar 42 38 Alarming 28.8 

Malawi 22 35 Alarming 21.8 

Mali 33 29 Alarming 26.9 

Mauritania 32 10 Serious 17.6 

Mozambique 24 44 Alarming 26.3 

Namibia 24 24 Serious 14.3 

Niger 40 32 Extremely alarming 32.4 

Rwanda 23 33 Alarming 22.3 

São Tomé and Principe 13 10 N/A N/A 

Senegal 17 20 Serious 15.4 

Sierra Leone 27 51 Extremely alarming 32.2 

Somalia 26 N/A N/A N/A 

Sudan 41 26 Alarming 20.5 

Swaziland 10 22 Serious 17.7 

Tanzania 22 44 Alarming 24.2 

The Gambia 17 29 Serious 17.3 

Togo 22 37 Alarming 23.1 

Uganda 23 19 Serious 17.1 

Zambia 20 46 Alarming 29.2 

Zimbabwe 17 47 Alarming 23.8 

Source: World Food Programme. 

Percentage of Total Population That Is Obese, by Country 

percent 

35 

30 

25 

20 

15 

10 

5 

0 

U.S. 

Mexico 

UK 

Slovakia 

Greece 

Source: NationMaster.com. 

Australia 

Hungary 

New Zealand 

Luxembourg 

Czech Republic 

Canada 

Spain 

Ireland 

Germany 

Portugal 

Finland 

Iceland 

Turkey 

Belgium 

Netherlands 

Sweden 

Denmark 

France 

Austria 

Italy 

Norway 

Switzerland 

Japan 

South Korea 

Weighted Average 


26 

Most Undernourished Countries, by Percent of Population Undernourished 

percent 

80 

70 

60 

50 

40 

30 

20 

10 

0 

Eritrea 

Congo, Dem. Rep. 

Burundi 

Tajikistan 

Sierra Leone 

Liberia 

Zimbabwe 

Ethiopia 

Haiti 

Zambia 

Central African Rep. 

Mozambique 

Tanzania 

Guinea-Bissau 

Madagascar 

Yemen 

Togo 

Angola 

Chad 

Malawi 

Cambodia 

Congo, Rep. of 

North Korea 

Rwanda 

Niger 

Kenya 

Bangladesh 

Mali 

The Gambia 

Nicaragua 

Cameroon 

Sudan 

Honduras 

Armenia 

Djibouti 

Guinea 

Namibia 

Pakistan 

Bolivia 

Guatemala 

Sri Lanka 

Swaziland 

India 

Benin 

Laos 

Uganda 

Philippines 

Nepal 

Occupied Palastine 

Source: World Food Programme. 


uitous threat to good health, while 

surpassing tobacco as the most predominant 

cause of preventable death 

in the U.S. (See the “Obesity Data” 

chapter for more charts and tables 

related to obesity and the world 

hunger epidemic.) 

The year 2010 marks the first time in 

modern history that any disease or 

detrimental human health condition 

has equaled the prevalence of world 

hunger. The specter of obesity, primarily 

prevalent in the most developed 

nations, now accounts for one over- 

Percentage of Overweight Women in Developing 

Countries, Compared to U.S. 

percent 

70 

60 

50 

40 

30 

20 

10 

0 

South Asia Sub-Saharan 

Africa 

Latin 

American/ 

Caribbean 

Eastern 

Europe 

Middle East/ 

North Africa 

Source: International Obesity Taskforce, citing International Food Policy 

Research Institute, 2001. 

The Inverted U of Wealth and Obesity 

Obesity Rate 

No obesity 

due to 

extreme 

poverty 

Source: Pure Pedantry. Sept. 26, 2007. 

Wealth 

Where this 

line goes is 

debateable 

No obesity 

due to good 

nutrition and 

exercise 

U.S. 

weight person to correspond to every 

human being suffering from povertyrelated 

hunger, mostly living in less 

developed regions, particularly African 

and Asian nations. 

Americans are spending $98.2 billion 

annually to combat excess weight gain 

and Medicare and Medicaid are straining 

their budgets paying approximately 

half of that total. The two agencies 

spend more on that patient group 

than any other. Meanwhile, developed 

nations are sending billions of dollars 

in foreign aid to try to combat world 

hunger. 

Does the BMI Contrive an Artificial 

Market for Drug Developers, Medtech 

Purveyors and Physicians? 

The widely accepted definition of an 

obese person is anyone with a body 

mass index (BMI) over 30.0. The definition 

of an overweight person is anyone 

with a BMI between 25.0 and 

29.9. These definitions are generally 

regarded as the obesity measurement 

standard by most in the field. The calculation 

used to determine the parameters 

for being regarded as overweight 

or obese is widely accepted by organizations 

that evaluate the bearing of 

weight in health-related matters and is 

unanimously used to calculate obesity 

and produce derivative statistics. 

Even so, it has many detractors that 

believe the defining measurement 

requirements are too simple. The 

WHO uses the formula, but defines 

the BMI as “a crude measurement of 

obesity,” insinuating the considerable 

ambiguity of a resolute acceptance for 

it as the designated disease yardstick. 

Critics ask why age and other components 

are omitted as factors in the BMI 

equation. It is common for people to 

lose height and gain weight as they 

age past 55 years; so, is it accurate to 

hold a 65-year-old to the same standards 

assigned a 22-year old? It is 

impossible for the elderly to match the 

same anti-obesity standard as an oth- 


28 

erwise physically fit young adult, no 

matter what level of fitness the senior 

adult achieves? Time on Earth ages 

and deteriorates the body of a human, 

and that decline cannot be utterly 

eliminated by physical exercise, therapeutic 

elixir or med-tech equipment. 

Critics argue that BMI is remiss and 

anecdotal in its designations, unless 

factors such as age, body fat percentage, 

gender and overall fitness are 

included. 

Observing and considering the size 

and fitness of Shaquille O’Neal, the 

accomplished National Basketball 

Association (NBA) star, one can wonder 

if he is fit or obese, or whether he 

is both concurrently. The medically 

professional answer is that, at 7’1” 

and 325 pounds, he is obese, with a 

BMI of 31.6. But he must be cleared 

for fitness by the NBA to endure the 

rigorous schedule and level of play 

required to participate in the league; 

therefore, it is possible to conclude 

that he is both fit and obese. If that is 

possible, then is it also possible that 

obesity, without symptoms, does not 

necessarily cause, or reflect, ill health? 

That would seem to signify that obesity 

is a probable trigger for other diseases, 

including diabetes, arthritis, 

asthma and heart disease, but is not a 

disease itself. Is it enough to say a person 

has a disease because he is 6”1’ 

and 225 pounds? 

Supporters say yes. They contend the 

BMI is no less subjective than the 

hypertension threshold of 120-over-80 

that doesn’t recognize additional factors 

such as age, gender or fitness 

level. Diseases are different and just 

because a BMI obesity-range reading 

does not signify disease or mortality as 

certainly as a temperature above 104 

degrees absolutely portends imminent 

health issues, it is nevertheless a valid 

barometer for measuring and predicting 

obesity onset and affliction prevalence. 

This debate should be regarded 

Health Insurance Coverage, U.S., Under 65 Years Old, 1984-2006 

percent 

100 

80 

60 

40 

20 

0 

1984 1989 1994 1999 2006 

Source: CDC/NCHS, National Health Interview Survey. 


in perspective, particularly noting that 

at the very least, obesity is perhaps the 

most prolific disease trigger in the 

world, contributing to the promulgation 

of the world’s most prevalent and 

deadly diseases. 

A primary argument by those not 

accepting obesity as a disease is the 

fact that the BMI parameters are too 

arbitrary and too minimal to factor the 

entire diverse range of human beings 

with various shapes, constitutions and 

vital signs, genealogies, fitness levels, 

etc. 

Defining Obesity 

Weight Body Mass Index 

Underweight

LeBron James, the superstar basketball 

player on the Cleveland Cavaliers, with 

a visibly fit physique and an apparent 

high level of physical fitness, is 6’8” 

and 250 pounds and is categorically 

overweight, according to his 27.5 BMI. 

Consider another NBA member whose 

physique belies the horrible burden of 

disease, as prescribed by the BMI. 

Dwight Howard, the Orlando Magic 

center, whose body exhibits no visible 

fat to the naked eye, is 6’11” of toned 

muscle, but surely must reflect some 

flaw in the BMI calculation process, 

inasmuch as he is, with a 27.0 BMI, 

alongside James, squarely in the overweight 

category of BMI, which is 

acknowledged as a medically valid 

barometer of health by the WHO, CDC, 

FDA, NIH, AARP, AMA . . . why, OMG! 

What hope is there for millions of the 

rest of us to keep from making the dubious 

list, if James and Howard are considered 

in need of therapeutic intervention 

to facilitate their health, according 

to BMI principles? 

Does BMI Settle the Debate, or Is 

the Visual Proof All Around Us? 

It could be legitimate to debate the 

BMI’s rigidity and, consequently, its 

validity in defining the parameters of 

obesity over the lifespan of a human 

being. Should a 20-something adult 

carrying 10 to 12 pounds of excess 

weight be evaluated differently from an 

80-something person, based on the 

bare criteria that circumscribe the BMI in 

designating ideal, overweight and 

obese body weight status? 

However the scales eventually tip in that 

debate, excess weight is still a problem 

that is increasing and showing no signs 

of abating. Even if the BMI overweight 

and obese benchmarks were increased 

by 10 points, BioWorld calculations 

would still put the percentage of overweight 

and obese Americans at approximately 

55 percent. That would still 

leave most of the newly downgraded 

11 percent taken out of the overweight/obese 

category on the cusp. 

It is not so important to define obesity 

as a disease itself, or as the world’s 

greatest disease risk factor. The bottom 

line is that obesity is a big fat 

problem that will be nothing short of a 

calamitous epidemic by 2030, unless 

therapeutic and med-tech treatment 

and curative agendas (along with public 

awareness and lifestyle changes) do 

not correspondingly grow to counteract 

the challenge. 

There will be medical and cosmetic 

facets to account for increasing sector 

value. Market growth is spurred by 

afflicted patients who can’t help themselves 

and by people affected by social 

and personal mores who just want to 

help themselves look or feel better. 

Market drivers are not only the genetically 

afflicted and the unhealthy habits 

demographic, but also an impulsive, 

impressionable consumer base that is 

anxious to be thin or healthy. 

The national and global preoccupation 

with being both appealingly lean in 

appearance and physically fit in 

healthiness is a dynamic that cannot 

be discounted. With the threshold of 

the BMI criteria set low enough to 

classify millions of marginally overweight 

and obese patients in the 

range to qualify for insurance coverage 

of the med-tech surgeries, the 

patient base that will actually have 

access to the products will increase in 

correspondence with the increase in 

applicable weight control surgeries. 

We Won’t Stop Eating, So We Must 

Keep Researching 

We eat when we are happy. We eat 

when we are sad. Food distracts us 

from boredom and increasingly is 

bringing out the innovation in chefs 

around the world who are expanding 

its culinary applications, along with 

our waistlines. The contemporary 

media agenda is peppered with culinary 

television programs, books, magazines, 

sections in the newspaper and 

websites that promote eating, even if 

offering occasional healthy selections. 

We use food to celebrate, honor, 

mourn, relax, cope, energize, sleep, 

entertain, train, compete and even kill. 

Everyone knows that the way to a 

man’s heart is through his stomach, as 

well as the way to a woman’s heart is 

to eat, and complement, her cooking. 

We supersize, then we clean our 

plates. We threaten our children when 

they contend to be full. We buy in 

bulk. We are legally force-fed when 

we refuse to eat and we are judged 

when we shed excessive weight. The 

majority of us are overweight in the 

U.S. and obesity, if not officially a 

chronic disease, should be pursued 

and treated like one. 

Sex, Sleep and Weight . . . Prurient 

Interests Augment Serious 

Markets 

Ideal sex, sleep and weight dominate 

the psyche of modern culture. Those 

are three obsessions, particularly in 

developed countries, as the populace 

is driven by hooking up, dozing off 

and slimming down. The subsidiary 

consumer base that can supplement 

the revenue stream for prescription 

products that address the chronically ill 

in those indications may be a dubious 

demographic, but it also can be an 

inestimable dynamic that will impact 

sales by adding a significant number 

of “casual users” to the market. 

There is evidence that the breakoutupon-approval 

market debut sales of 

two twenty-first century classes of drugs 

owed at least some their success to the 

advantage they had from the lifestyle 

implications of their applications, as well 

as life sciences ones. Better love life, better 

state of sleep, and coming soon . . . 

better mirror image! It may not be what 

the drug developers planned in their 

years-long R&D efforts, but it is a reality. 

Many drugs are overprescribed to marginally 

affected people, but the appeal 

of products in applications that address 

(not necessarily by intention) the popular 

culture areas that preoccupy society 

usually results in supplemental revenue. 


30 

Weight loss obsession is not too strong 

a phrase to describe the mania connected 

with the desire to be thin, and 

that obsession is verified by the $200 

billion annual expenditure to slim 

down by almost any means available. 

Everyone is America is estimated to 

know at least a dozen people who 

have expressed a desire to lose weight 

or who are engaged in activities that 

target weight loss. And who among us 

doesn’t have one or two “miracle” 

products stored in the attic, medicine 

cabinet, or in use, that purported to 

either “melt the pounds away, burn 

calories while you sleep, quadruple 

your metabolism, or flush the fat right 

down the toilet”? 

Because of the obsession of people, 

young and old, weighing anywhere 

from 50 to 500 pounds, this class of 

drugs is projected to have tremendous 

out-the-gate potential, due to the 

appeal of its indication. Everyone wants 

to lose weight (even those who don’t 

particularly need to) for motives ranging 

from health to peer pressure and vanity. 

The market for weight loss therapeutics 

is expected to explode upon arrival, 

inasmuch as the majority of Americans 

are already overweight or obese, and 

even a portion of the remaining percentage 

believe they could stand to 

lose a few pounds, even if just for aesthetic 

motives, rather than health-related 

ones. Although the current therapeutics 

are generally prescribed to critically 

obese people, some experts 

believe that future drugs in this space 

may be more widely prescribed, possibly 

treating patients who have only 10 

to 20 pounds to lose. Market growth is 

spurred by afflicted patients who can’t 

help themselves and by people affected 

by social and personal mores who 

just want to help themselves to look or 

feel better. Driving this market is not 

only a hunger binge trend in developed 

nations, but an impulsive consumer 

base that is either anxious to be thin or 

determined to be healthy. 


The expected market boom could 

trump the market head starts experienced 

by other two broadly anticipated 

markets that had lifestyle implications 

as well as medical applications: 

erectile dysfunction and sleep disorders. 

The trend for market success in 

the weight loss sector is projected to 

exceed the market debut runs of those 

cohort sectors that also had lifestyle 

implications that help to boost product 

revenue opportunities by incorporating 

a degree of consumer appeal 

with its semi-cosmetic application, to 

go along with the more critical medical 

application for severely-stricken 

patients. 

This is a market-in-waiting that is 

poised to gallop through the pharmacy 

upon approval. This forecast is comparable 

to when millions lined up in anticipation 

of ED drug market releases, not 

entirely for chronic conditions, rather to 

experience the promise of increased 

sexual stamina, and when many people, 

some with dubiously marginal 

affliction, overstated their cases in order 

to obtain the instant relief of a chemically 

induced good night’s sleep rather 

than affect a lifestyle change that might 

require sacrifice. 

Both classes of drugs have serious 

medical applications, but both have 

lifestyle appeal also. Weight loss 

obsession among the socially conscious 

and trendy is estimated to 

exceed the prurient appeal of even sex 

and sleep and is apt to increase market 

penetration for the impending round 

of obesity products. 

The Weight of the World to Come: 

Challenges and Issues of the 

Future Market 

There is little doubt that if everyone 

adhered to the BMI, the world’s population 

would benefit from the general 

and individual weight loss. It wouldn’t 

be absolved of disease and health 

afflictions, rather it would be just 

decidedly healthier than it is now. 

However, to supporters of the Disease 

Theory, such acknowledgement is not 

validation of the BMI or its validity to 

identify or predict disease. 

Debate may persist regarding how to 

define obesity, but the statistics bear 

out unmistakable facts: It is costing a 

lot of money to treat; it is an onset factor 

in most Type II diabetes cases; and 

more people are falling into the group, 

which has become the largest and 

fastest-growing health affliction category 

in the world. 

There is debate regarding whether or 

not obesity warrants the conventionally 

defined epidemic label ascribed to it 

by many authorities; however obesity 

is, at the least, an uncontrolled, spiraling 

problem. 

The ineffectiveness (on a meaningful, 

curative scale) of any individual, voluntary, 

organized or government resolution 

initiative to curtail or reverse the 

obesity problem puts the onus on a clinical 

response to address the problem. 

Biotechnology is on the forefront of that 

battle with innovative research, candidates 

poised to tackle the pervasive epidemic 

conditions, while med-tech is 

already a player with effective products 

and services, as well as a roster of novel 

technologies in development. 

Why hasn’t pharma stirred up a latestage 

partnering frenzy for biotech’s 

leading candidates? BioWorld concludes 

that the poor performance of 

the prescription drug market, as well 

as the significant number of clinical 

near-misses and failures, to date in 

the anti-obesity space would still 

require too big a leap of faith in 

biotech’s R&D at this point for big 

pharma to take. The most likely scenario 

will be an eleventh-hour Phase 

III deal or post-approval M&A activity. 

Also, if one of the candidates succeeds 

in getting FDA approval, the 

other two could then draw a lot of 

partnering attention. The three leading 

candidates show promise, but are

not inspiring optimism that they are 

the “magic pills” everyone is waiting 

for. Pharma is not an industry that 

operates on faith. That is biotech’s 

forte, inasmuch as innovation is predominantly 

born of faith. However, 

pharma’s strength (and weakness 

too) is its overreliance on evidence, 

and more impressive data will have to 

be submitted in order to knock their 

socks off enough to invest in a market 

that has been repeatedly tough to 

crack so far. 

Unmistakably, obesity is assured to 

remain a principal health challenge for 

decades to come. It is projected that 

significant progress will be made in 

treating that grossly unmet need. 

Billions of patients and millions of lives 

are hinging on the timeliness of effective 

med-tech and biotech products 

that are in need of VC financial backing 

and biopharma partnerships to 

hasten the development of R&D innovation 

that is moving at a much too 

sluggish pace to thwart an increasingly 

threatening global health and economic 

calamity . . . or whatever you 

choose to call it. 

BioWorld concludes that obesity represents 

a most fundamental therapeutic 

market for investors, health care 

givers, device manufacturers and drug 

developers to cast their lot. It is a market 

that could be controlled by a reversal 

of behavior by its patients; however, 

that base has shown little motivation 

to match its inclination to avoid or 

correct the disease. 

The collective willpower of the public 

may the biggest competition to 

biotech, med-tech and pharma 

being able to dominate the treatment 

market in this indication, but 

the collective arsenal of those three 

industries is, for the moment, just as 

intangible as society’s regimen of 

self-discipline. 


32 


Obesity Drugs: An Underweight Market 

Seeks Big Opportunites from a Growing Problem 

Obesity is a worldwide problem most 

obviously seen in developed countries. 

The Centers for Disease Control and 

Prevention estimates that more than a 

third of Americans – about 72 million 

people – are obese, and another third 

are overweight. 

If current trends continue, 43 percent 

of U.S. adults will be obese and obesity 

spending will quadruple to $344 billion 

by 2018, according to a study 

released in late 2009. On the other 

hand, if obesity rates hold steady, the 

U.S. would save nearly $200 billion in 

health care costs – or about $820 per 

adult. 

Based on research by Emory University, 

health care economist Ken Thorpe, 

executive director of the Partnership to 

Fight Chronic Disease, the report is the 

first to estimate obesity prevalence 

and costs at the state and national 

level 10 years from now. The report 

was commissioned by UnitedHealth 

Foundation, Partnership for Prevention 

and American Public Health 

Association in conjunction with their 

annual America’s Health Rankings 

report. 

“At a time when Congress is looking 

for savings in health care, this data 

confirms what we already knew: 

Obesity is where the money is,” 

Thorpe said. “Because obesity is related 

to the onset of so many other illnesses, 

stopping the growth of obesity 

in the U.S. is vital not only to our 

health – but also to the solvency of our 

health care system.” 

The report projects that obesity will 

comprise 50 percent of the adult population 

in six states, with an associated 

increase in health spending linked to 

obesity of more than $1,600 per person 

in each of these “worst” states: 

Kentucky, Maryland, Mississippi, Ohio, 

Oklahoma and South Dakota. 

Oklahoma is expected to have the 

highest obesity rate in the country by 

2018. The report projects that the 

state’s obesity rate will be 56.1 percent 

by then, and that obesity-attributable 

health care spending will be $1,906 

per adult. If obesity levels remain 

steady, however, it would provide a 

potential savings of $1,200 per adult 

or a savings of more than $3.2 billion 

for the state. 

According to the report, the obesity 

rate will stay below 35 percent in only 

four states and the District of 

Columbia. Nevertheless, the data 

shows that obesity-attributable health 

spending will climb to more than $800 

per person by 2018 in each of these 

“best” states: Colorado, Connecticut, 

Massachusetts, Virginia and the 

District of Columbia. Colorado is estimated 

to have the lowest obesity rate 

by 2018 – 29.8 percent. Obesityattributable 

health spending in 

Colorado is expected to be $864 per 

adult. 

Body Mass Index of U.S. Population 

BMI Description U.S. Population 

20-25 normal 

25-29.9 overweight 

30-39.9 obese 20 million 

40-50 morbidly obese 5-10 million 

Over 50 superobese up to 5 million 

Source: Biomedical Business & Technology. 

BIOTECH DRUGS FOR OBESITY 

According to the report, Thorpe and 

colleagues from Emory developed an 

economic model to estimate the 

growth of health care costs over time 

that are attributable to changes in 

obesity rates. They used nationally representative 

data on adults to estimate 

the effect of the increasing prevalence 

Obesity Rankings by State 

Obesity Prevalence, Top Five 

Mississippi 32.0% 

Alabama 30.3% 

Tennessee 30.1% 

Louisiana 29.8% 

West Virginia 29.5% 

Bottom Five 

Hawaii 21.4% 

Rhode Island 21.4% 

Massachusetts 21.3% 

Vermont 21.3% 

Connecticut 21.2% 

Colorado 18.7% 

Source: Centers for Disease Control 

and Prevention. 

Aggregate Medical Spending Attributable to Overweight 

and Obesity by Insurance Status and Data Source, 

1996–1998 (US$ billions) 

Insurance Overweight and Obesity Obesity 

Category MEPS (1998) NHA (1998) MEPS (1998) NHA (1998) 

Out-of-pocket $7.1 $12.8 $3.8 $6.9 

Private $19.8 $28.1 $9.5 $16.1 

Medicaid $3.7 $14.1 $2.7 $10.7 

Medicare $20.9 $23.5 $10.8 $13.8 

Total $51.5 $78.5 $26.8 $47.5 



34 

Estimated Adult Obesity-Attributable Percentages and Expenditures by State, 1998-2000 

% Total Millions $ % Medicare Millions $ % Medicaid Millions $ 

Population Population Population 

Alabama 6.3 $1320 7.7 $341 9.9 $269 

Alaska 6.7 $195 7.7 $17 8.2 $29 

Arizona 4.0 $752 3.9 $154 13.5* $242 

Arkansas 6.0 $663 7.0 $171 11.5 $180 

California 5.5 $7675 6.1 $1738 10.0 $1713 

Colorado 5.1 $874 5.1 $139 8.7 $158 

Connecticut 4.3 $856 6.5 $246 11.0 $419 

Delaware 5.1 $207 9.8 $57 13.8 $66 

D.C. 6.7 $372 6.5 $64 12.5 $114 

Florida 5.1 $3987 6.1 $1290 11.6 $900 

Georgia 6.0 $2133 7.1 $405 10.1 $385 

Hawaii 4.9 $290 4.8 $30 11.2 $90 

Idaho 5.3 $227 5.6 $40 12.0 $69 

Illinois 6.1 $3439 7.8 $805 12.3 $1045 

Indiana 6.0 $1637 7.2 $379 15.7 $522 

Iowa 6.0 $783 7.5 $165 9.4 $198 

Kansas 5.5 $657 6.4 $138 10.2* $143 

Kentucky 6.2 $1163 7.5 $270 11.4 $340 

Louisiana 6.4 $1373 7.4 $402 12.9 $525 

Maine 5.6 $357 5.7 $66 10.7 $137 

Maryland 6.0 $1533 7.7 $368 12.9 $391 

Massachusetts 4.7 $1822 5.6 $446 7.8 $618 

Michigan 6.5 $2931 7.8 $748 13.2 $882 

Minnesota 5.0 $1307 6.6 $227 8.6 $325 

Mississippi 6.5 $757 8.1 $223 11.6 $221 

Missouri 6.1 $1636 7.1 $413 11.9 $454 

Montana 4.9 $175 6.2 $41 9.8 $48 

Nebraska 5.8 $454 7.0 $94 10.3 $114 

Nevada 4.8 $337 5.0 $74 10.1* $56 

New Hampshire 5.0 $302 5.4 $46 8.6* $79 

New Jersey 5.5 $2342 7.1 $591 9.8 $630 

New Mexico 4.8 $324 4.6 $51 8.5 $84 

New York 5.5 $6080 6.7 $1391 9.5 $3539 

North Carolina 6.0 $2138 7.0 $448 11.5 $662 

North Dakota 6.1 $209 7.7 $45 11.7 $55 

Oklahoma 6.0 $854 7.0 $227 9.9 $163 

Ohio 6.1 $3304 7.7 $839 10.3 $914 

Oregon 5.7 $781 6.0 $145 8.8 $180 

Pennsylvania 6.2 $4138 7.4 $1187 11.6 $1219 

Puerto Rico 7.4 8.1 10.1 

Rhode Island 5.2 $305 6.5 $83 7.7 $89 

South Carolina 6.2 $1060 7.7 $242 10.6 $285 

South Dakota 5.3 $195 5.9 $36 9.9 $45 

Tennessee 6.4 $1840 7.6 $433 10.5 $488 

Texas 6.1 $5340 6.8 $1209 11.8 $1177 

Utah 5.2 $393 5.8 $62 9.0 $71 

Vermont 5.3 $141 6.9 $29 8.6 $40 

Virginia 5.7 $1641 6.7 $320 13.1 $374 

Washington 5.4 $1330 6.0 $236 9.9 $365 

West Virginia 6.4 $588 7.3 $140 11.4 $187 

Wisconsin 5.8 $1486 7.7 $306 9.1 $320 

Wyoming 4.9 $87 5.9 $15 8.5 $23 

Total 5.7 $75,051 6.8 $17,701 10.6 $21,329 

*Estimates based on fewer than 20 observations. 

Source: The Obesity Society, citing Obesity Research, Vol. 12, No. 1, January 2004, Finkelstein, et al., pages 22-23. 


of obesity on total direct health care 

costs. Estimates are controlled for age, 

gender, race, ethnicity, marital status, 

education, income, health insurance 

status, geographic region and smoking 

status, the report noted. 

Obesity is growing faster than any previous 

public health issue the U.S. has 

faced, Thorpe and colleagues noted in 

the report. If current trends continue, 

103 million American adults will be 

considered obese by 2018, the report 

said. The report also says that obesity- 

Rising Costs of Obesity 

billions of US dollars 

160 

140 

120 

100 

80 

60 

40 

20 

0 

1998 2008 

Source: The Wall Street Journal. 

Medications That Promote Weight Loss 

related direct expenditures are expected 

to account for more than 21 percent 

of the nation’s direct health care 

spending in 2018. 

The rise in the prevalence of adult obesity 

has been well documented over 

the last 20 years, according to the 

report, increasing from 12 percent in 

1989 to 27 percent in 2008. Thorpe 

and colleagues noted that the true 

prevalence of obesity is likely to be 

substantially higher, however, as it has 

been shown to be under-reported by 

about 9.5 percent, because people 

tend to understate their weight on 

telephone surveys. 

With the overall U.S. market for 

weight-loss remedies and diet products 

sitting at more than $50 billion, 

the obesity market has been touted as 

a potential goldmine. In the U.S., drug 

options for obesity include the generic 

drug phentermine, F. Hoffmann-La 

Roche Ltd.’s Xenical (orlistat) and 

Abbott’s Meridia (sibutramine HCl 

monohydrate capsules C-IV) and nonprescription 

Alli (low-dose orlistat, 

GlaxoSmithKline plc). But despite 

these few successes, it’s been more of 

a graveyard, littered with the failures 

of Pfizer Inc.’s CP-945,598, Merck & 

Co. Inc.’s taranabant, Sanofi-Aventis 

Group’s Acomplia (rimonabant) and 

Wyeth’s Fen-Phen (dexfenfluramine/ 

phentermine). Even the drugs that have 

made it to market (and stayed there) 

have offered modest efficacy, troubling 

side effects and disappointing sales. 

Prescription pharmaceutical products 

account for less than 1 percent of the 

total obesity market, while surgery is 

viewed as the most effective option for 

morbidly obese patients. But that may 

be about to change. 

Globally, the World Health Organization 

projects that 400 million adults are 

obese and 1.6 billion are overweight. 

Those figures are expected to grow to 

700 million and 2.3 billion, respectively, 

by 2015. But most folks don’t need statistics 

to convince them that obesity is a 

problem; one trip to a local shopping 

mall, gym, airport or restaurant is usually 

enough to observe and verify the 

world's expanding waistline. 

Top Obesity Candidates Reveal 

Promising Data, but Get No 

Promises from Pharma 

Investors – and prospective partners – 

hoping that detailed data emerging 

from October 2009’s Obesity Society 

meeting in Washington might shed 

more light on the three frontrunners in 

the weight loss drug race came away 

Name Maker FDA Approval for Weight Loss Drug Type 

Meridia/Reductil (sibutramine) Abbott Yes; long term (up to 1 year) for adults appetite suppressant 

Ionamin/Adipex-P (phentermine) Medeva Pharma Yes; short term (up to 12 weeks) for adults appetite suppressant 

Gate Pharma 

Tenuate (diethylpropion) Yes; short term (up to 12 weeks) for adults appetite suppressant 

Bontril (phendimetrazine) Yes; short term (up to 12 weeks) for adults appetite suppressant 

Xenical/Alli (orlistat) Roche, Yes; long term (up to 1 year) for adults and lipase inhibitor 

GlaxoSmithKline children age 12 and older 

Wellbutrin, Zyban (bupropion) GlaxoSmithKline No depression treatment 

Topamax (topiramate) Johnson & No seizure treatment 

Johnson 

Zonegran (zonisamide) Eisai No seizure treatment 

Glucophage/Glumetza (metformin) Bristol-Myers No diabetes treatment 

Squibb 

Byetta (exenatide) Eli Lilly No diabetes treatment 

Symlin (pramlintide) Amylin Pharma No diabetes treatment 

Source: BioWorld research and the Weight-control Information Network, from the National Institute of Diabetes and Digestive and 

Kidney Diseases. 


36 

Percentage of U.S. Adults Who Are Overweight or Obese 

66 percent 

(143 million) 

Total Women Men 

Source: Centers for Disease Control and Prevention, National Center for Health Statistics and BioWorld-adjusted-for-2010 data. 

Percentage of U.S. Adults Who Are Obese 

32 percent 

(72 million) 


62 percent 

(70 million ) 

34 percent 

(39 million) 

71 percent 

(73 million) 


30 percent 

(33 million) 

Source: Centers for Disease Control and Prevention, National Center for Health Statistics and BioWorld-adjusted-for-2010 data. 

Percentage of U.S. Adults Who At a Healthy Weight 

32 percent 

(69 million) 

36 percent 

(40 million) 


28 percent 

(29 million) 

Source: Centers for Disease Control and Prevention, National Center for Health Statistics and BioWorld-adjusted-for-2010 data.

with some more promising data on 

each but no clear winner. That “large 

bolus of data may be overwhelming 

for some physicians to quickly 

absorb,” analyst Elemer Piros, of 

Rodman & Renshaw, wrote in a 

research note. Those doctors, he 

added, “will ultimately determine their 

drug of choice based on personal 

experience,” though average weight 

loss data are sure to remain “one of 

the key selling messages.” 

In terms of weight loss data, the combination 

drugs generally have prevailed. 

Previously reported top-line figures 

put placebo-adjusted weight loss 

numbers as high as 9.4 percent and 

8.6 percent in two Phase III trials of 

Vivus Inc.’s Qnexa (phentermine/topiramate), 

while Orexigen Therapeutics 

Inc.’s Contrave (bupropion SR/naltrexone 

SR) came in at 4.2 percent to 5.2 

percent. Vivus filed an NDA for Qnexa 

in December 2009. Analysts expect 

Orexigen to file an NDA for Contrave 

in early 2010. 

Arena Pharmaceuticals Inc.’s lorcaserin, 

a 5-HT2c serotonin receptor agonist, 

came in at the lower end, with a 3.6 

percent placebo-adjusted weight loss 

in its first Phase III study. But lorcaserin’s 

clean safety data could give it a 

foothold in the market. Piper Jaffray 

analyst Edward Tenthoff called safety 

“a key factor” for FDA approval and 

partnering potential. And lorcaserin 

“appears to be the safest of these 

three agents with side effects not 

meaningfully different than placebo,” 

he wrote in a research note. Arena 

filed an NDA for lorcaserin in 

December 2009. 

But as of early 2010, none of the 

three late-stage products had managed 

to snag a partnership. 

San Diego-based Arena said it is 

actively seeking a big pharma partner 

to reach the broad primary care space. 

Orexigen, also of San Diego, intends 

to build its own sales force to reach 

Company Survey Asking, ‘What Aspects of Obesity Do 

Your Discovery Research and Drug Candidates Address?’ 

Dual antiobesity / 

antidiabetic agents 

Neurotransmitter 

receptor agonists 

or antagonists 

Gut hormone 

mimetics 

Others 

Neuropeptide 

mimetics 

Pancretic lipase 

inhibitors or similar 

Combination of 

drugs with different 

mechanisms 

Adipokine 

mimetics 

Source: Insight Pharma Reports. 

the specialty market while looking for 

a larger collaborator for the primary 

care space and ex-U.S. territories, and 

Mountain View, Calif.-based Vivus 

entered partnering mode after reporting 

the last of its Phase III trials earlier 

in 2009. 

Industry experts had been expecting 

data from the obesity meeting to help 

gauge big pharma interest. Overall, 

results presented at the conference 

offered no big surprises. As JMP 

Securities analyst Jason N. Butler 

noted, none of the data “will move 

the needle dramatically in terms of our 

approval and commercial potential.” 

But they could help to differentiate 

each product’s marketing profile if all 

three reach the market, as many analysts 

predict. 

Data on Vivus’ Qnexa showed that the 

drug’s effect was consistent across all 

levels of body mass index in the EQUIP 

trial, which tested low-dose and fulldose 

versions in 1,267 morbidly obese 

patients. And a measure of excess 

body weight loss was 42 percent in 

the intent-to-treat population of the 

CONQUER study, which enrolled 

6 

9 

11 

14 

19 

20 

2,487 overweight and obese patients 

with high blood pressure, high cholesterol 

or Type II diabetes. 

Excess body weight loss (EBWL) data, 

while not specifically among the FDA 

requirements for obesity drugs, were 

highlighted by each company at the 

annual conference. 

In two Phase III trials, Orexigen’s 

Contrave demonstrated an EBWL of 

30 percent and 31.7 percent vs. placebo 

rates of 6.7 percent and 4.7 percent. 

The product also produced significant 

improvements in markers for 

cardiometabolic risk and reduced 

HbA1c levels in patients with Type II 

diabetes who began the trial with an 

HbA1c level greater than 8 percent. 

Additionally, Contrave patients reported 

an increased ability to control their 

eating and resist food cravings. 

New data from Arena’s BLOOM study, 

which barely met its endpoints earlier 

in 2009, showed that patients on lorcaserin 

who completed the trial 

according to protocol lost 31 percent 

of their excess weight compared to 12 

percent in the placebo group. And tol- 

THE BIOWORLD AND MEDICAL DEVICE DAILY OBESITY REPORT 37 

26 

35

38 

erability data was consistent with 

results previously reported, with no 

increase in depression or suicidal 

ideation compared to placebo. 

Though two suicide attempts were 

reported in the trial, those events were 

not believed to be related to the drug. 

Solving The Obesity Compound 

Conundrum: Where's Big Pharma? 

Late-stage biotech drugs addressing 

potentially blockbuster markets aren’t 

exactly falling off the trees and into 

big pharma’s lap, yet the three leading 

biotech assets in the obesity space – 

Vivus Inc.’s Qnexa, Arena 

Pharmaceuticals Inc.’s lorcaserin and 

Orexigen Therapeutics Inc.’s Contrave 

– remained unpartnered as of early 

2010. Why? 

Is it because big pharma isn’t interested? 

Obesity has proven a disappointing 

gamble for drugmakers thus far. 

There have been late-stage discontinuations, 

such as Pfizer Inc.’s CP-945,598 

and Merck & Co. Inc.’s taranabant. 

Product recalls, too, such as Sanofi- 

Aventis Group’s Acomplia (rimonabant) 

and Wyeth’s infamous Fen-Phen 

(dexfenfluramine/phentermine). (See 

the section, “Discontinued Products 

and Programs Are Prevalent in Obesity 

Space.”) 

Even those that have made it to market 

haven’t been all that successful. F. 

Hoffmann-La Roche Ltd. doesn’t break 

out sales of Xenical (orlistat), but various 

reports have pegged it at around 

$100 million annually. Ditto for 


monohydrate capsules C-IV). 

GlaxoSmithKline plc’s over-the-counter, 

low-dose version of Xenical, called 

Alli, generated just $139 million in 

worldwide sales last year. 

Adam Cutler, analyst with Canaccord 

Adams Inc., said Qnexa, lorcaserin and 

Contrave each represent improvements 

over what’s now available. He 

predicted that Qnexa and Contrave 

could each generate peak U.S. annu- 


al sales of $1 billion and lorcaserin 

could bring in $850 million – any of 

which should be enough to generate 

“significant interest” from potential 

partners. 

The lack of partnering activity even 

through Phase III trials and NDA filings 

could be due to several factors, Cutler 

said. First, when Vivus, Arena and 

Orexigen were looking to partner 

before Phase III, many of the big pharmas 

had their own late-stage obesity 

programs – programs that have since 

failed. Second, the three biotechs 

probably set prohibitively high prices 

back then, realizing that if they held 

on to their rights and funded their 

own Phase III programs, they could get 

much more money later. Third, pharma 

was likely just fine with that strategy, 

since the drug giants are willing 

to pay more money later if it means 

avoiding risk, Cutler said. 

Phase III data started trickling out in 

2008, leading to inevitable comparisons 

between the three programs. 

Vivus’s Qnexa, which combines the 

generic diet drug phentermine with 

epilepsy drug topiramate, looked to be 

the efficacy front-runner, as its first 

trial met both of the FDA’s goals. The 

FDA wants obesity drugs to show 

either 5 percent placebo-adjusted 

weight loss or twice as many patients 

losing 5 percent of their weight on 

drug vs. placebo, and Qnexa had 

placebo-adjusted weight loss of 7.5 

percent, with 66 percent of Qnexa 

patients vs. 15 percent of placebo 

patients losing more than 5 percent of 

their weight. 

Arena’s lorcaserin, a 5-HT2c serotonin 

receptor agonist, hit the FDA’s second 

goal but missed the first in its initial 

Phase III go-round. Placebo-adjusted 

weight loss was just 3.6 percent, but 

47.5 percent of lorcaserin patients vs. 

20.3 percent of placebo patients lost 

more than 5 percent of their weight. 

Orexigen’s Contrave, which combines 

the opioid blocker naltrexone with the 

dopamine stimulator bupropion, 

appeared to fall short of both FDA goals 

in its first Phase III, thanks to an intensive 

behavior modification program that created 

strong placebo results. But three 

additional Phase III trials released in July 

2009 met the FDA’s second parameter. 

Placebo-adjusted weight loss was 

between 4.8 percent and 5.2 percent 

for the two non-diabetic trials, and the 

percent of patients to lose more than 5 

percent of their weight was 48 percent, 

56.3 percent and 44.5 percent 

compared to placebo values of 16.4 

percent, 17.1 percent and 18.9 percent 

in the three trials. 

As for real-world potential, two obesity 

specialists interviewed by Cowen & 

Co. picked Contrave for its risk/benefit 

ratio. They also liked the fact that its 

ingredients both control addictive 

behavior, which may help with cravings, 

and they predicted it will have 

the easiest reimbursement of the three 

competitors. The doctors voiced concerns 

about Qnexa’s high rates of 

paresthesia (a prickly skin sensation) 

and the fact that its two generic components 

already are widely used and 

combined, which could cap pricing 

potential. They also predicted that lorcaserin’s 

modest efficacy would limit 

its use, although it might one day fare 

better if combined with phentermine. 

Rodman & Renshaw analyst Elemer 

Piros wrote in a research note that 

potential partners “will likely wait” 

until all the data are in before closing 

any deals. But Cutler isn’t so sure. He 

told BioWorld he thinks potential partners 

were just waiting for complete 

Phase III data on any single drug. 

By the time any parties likely finish due 

diligence on the Contrave data that has 

been released, though, the rest of the 

data for Qnexa and lorcaserin will be 

available. Partners might want to look 

at those, too, which would push the 

timeline closer to advisory committee 

meetings and approvals, thus tempting

pharma to wait even longer. Cutler cautioned 

that “any company interested in 

the space should be worried they’re 

going to miss out” by waiting too long, 

but he also noted that the three 

biotechs are unlikely to agree to a “surprise” 

deal without going back to all 

interested parties and playing them off 

one another to drive the price higher. 

As for which companies are likely to be 

shopping for obesity drugs, Leerink 

Swann analyst Steve Yoo pointed to 

large pharmaceutical companies with 

primary care sales forces as well as some 

specialty pharma firms. In addition, he 

noted that some dealmaking has picked 

up among Japanese companies looking 

to move into the obesity space. Yoo also 

noted that Sanofi-Aventis was once in 

the space with rimonabant (Acomplia). 

The Paris-based drugmaker ran into 

trouble after European regulators raised 

safety concerns, and the product never 

entered the U.S. market. Merck and 

Pfizer Inc. both had discontinued obesity 

programs in the same class as 

Acomplia that act against the cannabinoid 

receptor 1. “That tells us big pharma 

companies were thinking about 

obesity,” Yoo said. 

How Much Longer? Pharma Resists 

the Lure of an Underserved 

Goldmine Market 

A big question in the obesity space is 

why the pharmaceutical industry hasn’t 

found a way to successfully tap this 

market. The demand is certainly there, 

but the meager market penentration of 

pharma's current roster of approved, but 

barely effective, drugs may have shaken 

its confidence in its ability to significantly 

address the market. According to a 

report from JPMorgan Securities Inc., the 

overall U.S. market for weight-loss remedies 

and diet products was more than 

$50 billion in 2006. Yet prescription 

pharmaceutical products accounted for 

just $200 million in 2007 – less than 1 

percent of the total market. JPMorgan 

analyst Cory Kasimov said the explanation 

is “really quite simple: There are no 

safe and effective drugs.” 

Obesity Drugs in Development 

Drug name Company Phase 

Lorcaserin Arena NDA filed 

Qnexa (phentermine/ Vivus NDA filed 

topiramate) 

Contrave (naltrexone SR/ Orexigen Phase III 

naltrexone SR) 

Victoza (liraglutide) Novo Nordisk Phase III 

ATL-962 (cetilistat) Alizyme and Takeda Phase III (Japan) 

Symlin with metreleptin Amylin Phase IIb 

(pramlintide/metreleptin) 

Histalean Obecure Phase IIb 

Empatic Orexigen Phase IIb 

Tesofensine NeuroSearch Phase IIb 

SLx-4090 Surface Logix Phase IIb 

AR9281 Arete Phase IIa 

S-2367 (Velneperit) Shionogi Phase IIa 

Davalintide (AC2307) Amylin and Takeda Phase II 

TTP435 TransTech Phase II 

TM30339 7TM Pharma Phase I/II 

Obinepitide 7TM Pharma Phase I/II 

PSN821 OSI Phase I 

PSN602 OSI Phase I 

AZD4017 AstraZeneca Phase I 



PYY Emisphere Phase I 

HPP404 TransTech Phase I 

SLx-2119 Surface Logix Phase I 

ZGN-433 Zafgen Phase I 

TM38837 7TM Pharma preclinicals 

CORT 108297 Corcept preclinicals 

Ghrelin antagonist Elixir preclinicals 

SIRT1 activator Elixir preclinicals 

INT-777 Intercept preclinicals 

MPI-0485520 Myriad preclinicals 

OBE102 Obecure preclinicals 

UGP281 Unigene preclinicals 

XOMA 052 XOMA preclinicals 

ZP2929 Zealand Pharma preclinicals 

5HT-6 antagonists Esteve preclinicals 

GRC 9332 Glenmark preclinicals 

Anti-obesity product LG Life Sciences preclinicals 

MCR-4 compound Palatin and AstraZeneca preclinicals 

To be determined Targacept preclinicals 

TZP-301 Tranzyme preclinicals 

11ß HSD-1 inhibitors Vitae preclinicals 

AEZS-123 AEterna Zentaris in vivo testing 

ANG2004: EPiC Leptin Angiochem discovery 

TGFTX2 Genfit discovery 

SCD1 inhibitors Xenon and Novartis discovery 

Compound targeting Surface Logix discovery 

Enteric incretin 

PPAR compounds Plexxikon and Wyeth development 

SIRT2 inhibitor Elixir research 

NOX-B11 Noxxon research 

ITCA 880 Intarcia feasibility 

Source: BioWorld research from BioWorld Today and company websites. 


40 

In the U.S., prescription drug options 

for obesity include the generic drug 

phentermine, F. Hoffmann-La Roche 

Ltd.’s Xenical (orlistat) and Abbott’s 

Meridia (sibutramine HCl monohydrate 

capsules C-IV). 

Phentermine is the most prescribed 

obesity drug, but its placebo-adjusted 

weight loss is only 3 percent to 5 percent, 

and its amphetamine-like action 

and abuse potential limit it to shortterm 

usage. 

Xenical works in the gut, inhibiting gastric 

and pancreatic lipases to decrease 

the absorption of dietary fat. A metaanalysis 

of clinical trial data showed 

that Xenical’s average placebo-adjusted 

weight loss was 2.9 percent, with a 

drop-out rate of 30 percent. 

Meridia didn’t fare much better, with a 

4.2 percent weight loss and 31 percent 

drop-out rate. The drug works in 

the brain to signal a sense of fullness 

by inhibiting the reuptake of norepinephrine, 

serotonin and dopamine. 

And then there’s Sanofi-Aventis 

Group’s Acomplia (rimonabant). 

Marketing was suspended in Europe in 

October 2009. It was withdrawn from 

the FDA registration process in mid- 

2007 after a negative advisory committee 

panel. The drug blocks 

cannabinoid-1 (CB1) receptors in the 

brain, liver and gastrointestinal tract to 

regulate glucose and fat absorption 

and suppress appetite. Data from the 

meta-analysis showed a placeboadjusted 

weight loss of 4.7 percent 

and a 40 percent drop-out rate. 

The FDA said in a guidance document 

that it wants to see at least a 5 percent 

placebo-adjusted weight loss from obesity 

drugs. Although weight loss of 5 

percent to 10 percent has been shown 

to significantly decrease health issues 

associated with obesity, Kasimov said in 

his report that “meaningful weight loss 

for patients and physicians in the ‘real 

world’ is between 10 and 20 percent.” 


Combination Drugs Could Deliver 

Twice the Efficacy and Billions in 

Market Potential 

Building a better obesity drug is no 

easy task. Obesity involves a host of 

genetic, behavioral, emotional and 

socio-cultural factors. And any successful 

drug will be taken by millions 

of patients, resulting in a safety hurdle 

that will “probably be greater than for 

any other drug out there,” said 

JPMorgan analyst Cory Kasimov. 

But the physician consultants 

JPMorgan spoke with believe single 

agents will have “limited benefit 

because they can only target one 

pathway effectively, which is likely 

insufficient to produce long-term, sustained 

weight loss.” The doctors 

believe that “the combination 

approach will become standard of 

care,” Kasimov wrote. As evidence, 

Kasimov points out that the only prescription 

drug ever to produce significant 

weight loss and take the obesity 

market by storm was, in fact, a combination 

drug. The infamous Fen-Phen, 

prior to being recalled for safety 

issues, demonstrated 15 percent 

weight loss and generated more than 

20 million prescriptions annually. 

Today’s combination drugs for obesity 

are built from generics, which Kasimov 

said allows their safety profiles to be 

well understood. Two advanced products 

are Orexigen Therapeutics Inc.’s 

Contrave and Vivus Inc.’s Qnexa. 

For example, Orexigen’s Contrave 

combines long-acting versions of naltrexone, 

an opioid blocker approved 

for opioid and alcohol addiction, and 

bupropion, a dopamine stimulator 

approved for depression and smoking 

cessation. Orexigen’s former president 

and CEO, Gary Tollefson, explained 

that the two drugs affect the reward 

pathways associated with food addictions, 

both on the involuntary level 

that regulates hunger and energy 

burn, and on the voluntary level that 

causes excessive eating. Additionally, 

bupropion enhances weight loss by 

increasing energy burn, a normally 

short-lived benefit that naltrexone 

helps to extend. And bupropion has 

anti-depressive effects, addressing a 

frequent co-morbidity of obesity. Data 

from combined clinical trials show an 

average weight loss of 4.6 percent 

after 24 weeks on Contrave, similar to 

what the existing drugs produce over 

a year. Yet while other drugs hit a 

plateau, Contrave provides a “slow, 

steady, progressive reduction in 

weight,” Tollefson said, and patients 

completing a year of treatment 

achieved 8 percent to 10 percent 

reductions. 

Even more dramatic weight loss may 

come from Orexigen’s second product 

candidate, Empatic, a combination of 

long-acting bupropion and long-acting 

zonisamide, a seizure drug 

believed to modulate sodium channels 

and enhance dopamine and serotonin 

activity. The zonisamide inhibits neurons 

that contribute to the weight loss 

plateau by promoting energy storage 

and hunger when weight starts to 

drop off. This ability to prevent weight 

gain synergizes with bupropion’s ability 

to promote weight loss. Pooled trial 

data show Empatic offers average 

weight loss of 7.5 percent after 24 

weeks, which increased to 14 percent 

after a year according to Phase IIb data 

presented last month. The drug also 

has a drop-out rate of just 9 percent to 

21 percent, which Tollefson said was 

due to the company’s reformulation of 

zonisamide to limit side effects. 

Empatic is in Phase IIb trials, and Phase 

III trials initially were planned for 2009. 

Meanwhile, Orexigen is expected to 

file an NDA for Contrave in early 

2010. 

Vivus’s Qnexa also seeks to create a 

synergistic effect by combining the 

generic diet drug phentermine with 

topiramate, a drug approved for 

epilepsy and for migraine prevention. 

Phentermine decreases appetite and

increase energy usage, while topiramate 

increases feelings of fullness. 

Separately, the two drugs have only 

mild weight loss effects, but together 

they produce “true synergy” due to 

the fact that they target different areas 

in the brain, said Vivus Director of 

Clinical Development Barbara Troupin. 

She added that the two drugs also 

mitigate each other’s side effects, 

since topiramate tends to dull the 

senses while phentermine stimulates 

them. Qnexa also uses low doses of 

both drugs to decrease the incidence 

of side effects. So far, the synergy 

appears to be working. In a Phase II 

trial, Qnexa produced average placebo-adjusted 

weight loss of 8.6 percent 

in 24 weeks, with a drop-out rate of 

just 8 percent. JPMorgan’s physician 

consultants said they believe the product 

“may potentially have a best-inclass 

clinical profile.” But analysts have 

expressed concern about the fact that 

the Phase II trial was conducted at a 

single trial site. 

In the end, Kasimov predicted that the 

risk associated with the drugs will 

come from regulatory and commercial 

issues. That’s where the expertise of a 

big pharma partner will come in 

handy, he said, adding that it’s “a 

question of when, not if” the three 

drugs will eventually be partnered. 

Once they are, he expects all three to 

find a place in the obesity market, 

which he said has “room for multiple 

players.” Kasimov projected that as 

these and other new products gain 

approval, the market for prescription 

obesity drugs will grow from $200 million 

in 2007 to $1.5 billion in 2012 

and more than $4.6 billion in 2017. 

Arena Pharmaceuticals – lorcaserin 

Arena Pharmaceuticals Inc., of San 

Diego, submitted a new drug application 

to the FDA for weight loss drug 

candidate lorcaserin in December 

2009. In addition to the pivotal program, 

Arena is evaluating lorcaserin, a 

5-HT2c serotonin receptor agonist, in 

obese and overweight patients with 

Market for Prescription Obesity Drugs, 2007-2017 

millions of US$ 

5,000 

4,500 

4,000 

3,500 

3,000 

2,500 

2,000 

1,500 

1,000 

500 

0 

2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 

Source: BioWorld research. 

Type II diabetes in its BLOOM-DM trial. 

BLOOM-DM is planned as a supplement 

to the NDA. Cowen & Co. analyst 

Phil Nadeau stated that an FDA 

advisory panel meeting on lorcaserin is 

likely to occur in third quarter 2010 

and said consultants to his firm generally 

expect the FDA to approve the 

drug. 

Data Show Low Abuse Potential 

for Lorcaserin 

Earlier in December 2009, Arena reported 

that positive data from a clinical trial evaluating 

the abuse potential of lorcaserin 

were presented in a poster session at the 

48th Annual Meeting of the American 

College of Neuropsychopharmacology. 

Data from the trial demonstrate that the 

risk for abuse associated with lorcaserin 

is very low. 

Arena Reports Data from BLOS- 

SOM Phase III Study of Lorcaserin 

In October 2009, Arena reported data 

from the pivotal BLOSSOM Phase III 

study of lorcaserin showing highly significant 

improvements or favorable 

trends compared to placebo in multiple 

secondary endpoints, including 

body composition, cardiovascular risk 

factors and quality of life. Those findings, 

presented at the Obesity Society 

meeting in Washington, add to the 

top-line data presented earlier in that 

year, which showed a significant 

weight loss in patients receiving one 

year of treatment with lorcaserin. 

Lorcaserin’s Data Offset Modest 

Efficacy 

Much-anticipated data from Arena 

Pharmaceuticals’ second Phase III study 

of lorcaserin didn’t wow investors 

immediately when released in 

September 2009, but the drug’s impressive 

safety and tolerability profile left 

many analysts encouraged that it could 

find a place among stronger competitors 

in the growing obesity market. 

Results from intent-to-treat analysis 

showed that the BLOSSOM trial satisfied 

(barely) the efficacy benchmark set 

by the FDA for obesity drugs. The FDA’s 

guidance calls for at least 35 percent of 

patients losing at least 5 percent of 

baseline weight and that proportion of 

patients should be at about twice the 

proportion of patients losing at least 5 

percent in the placebo group. 


42 

Intent-to-treat data from BLOSSOM 

showed that 47.2 percent of twicedaily, 

lorcaserin-treated patients 

achieved at least a 5 percent reduction 

in baseline weight at 52 weeks, but 

that figure wasn’t exactly double the 

25 percent in the placebo arm. 

Though a few worries surfaced on 

how FDA reviewers might define 

“approximately double,” most analysts 

seemed to think lorcaserin’s efficacy 

data, though not stellar, are sufficient 

for approval. As Phil Nadeau, of 

Cowen and Co., put it in a research 

note: “If this was a field goal, it would 

have hit the upright and bounced 

through.” 

Data were consistent with results from 

the earlier BLOOM study, which 

showed that 47.5 percent of lorcaserin 

patients vs. 20.3 percent of placebo 

patients lost more than 5 percent of 

their weight and the drug was well 

tolerated. 

Results from the 4,008-patient BLOS- 

SOM trial also showed that a quartile 

of lorcaserin patients with the greatest 

weight loss at week 52 lost an average 

of 35.1 pounds, or 16.3 percent of 

their body weight. “So this is a very 

effective drug,” said Dominic Behan, 

Arena co-founder and chief scientific 

officer. 

The adverse event rate in the lorcaserin 

group did not exceed the 

placebo group by more than 4 percent. 

And importantly, no cardiovascular 

concerns were raised regarding 

heart valve insufficiency, with rates of 

valvulopathy reported at 2 percent in 

both the twice-daily lorcaserin group 

and placebo arm. Data from more 

than 7,000 patients in the BLOOM and 

BLOSSOM studies, using FDA criteria, 

effectively ruled out the valvulopathy 

risk, Behan added. 

Arena is hoping that lorcaserin’s safety 

data will make it a compelling replacement 

for approved but side-effectplagued 

phentermine. “You have to 


look at the overall market,” Behan 

told BioWorld. With phentermine as 

one of the few options, “it’s a very dissatisfied 

market. Physicians need a 

drug they can prescribe to the majority 

of patients” that offers rapid weight 

and is safe enough to encourage longterm 

compliance. 

A few analysts even suggested that 

lorcaserin, a 5-HT2c serotonin receptor 

agonist, could be used in combination 

with phentermine for more dramatic 

results. “There might be some physicians 

that might be interested in doing 

that,” Jack Lief, Arena’s president and 

CEO, acknowledged during a conference 

call, though he added, “I think 

[lorcaserin’s] marriage of efficacy, safety 

and tolerability” is compelling 

enough to persuade doctors to switch 

from phentermine to lorcaserin 

monotherapy. 

Arena had not conducted any combination 

trials as of late 2009, but Behan 

said the firm does hold patents allowing 

for combination therapy. “In the 

future, we might look into that, but 

we don’t need to go there to have a 

very effective agent,” he said. “And 

phentermine is not the only possible 

combination.” 

Arena’s next step is to secure a big 

pharma partner that can reach the primary 

care space, a task also facing 

potential competitors Vivus Inc. and 

Orexigen Therapeutics Inc. But while 

analysts have maintained that the obesity 

space clearly is large enough for all 

three products to snare a substantial 

portion – and despite all three products 

meeting Phase III goals – big pharma 

has stayed cautiously on the sidelines, 

likely due to the checkered past of the 

obesity field. “It’s been a challenge for 

big pharma to access the obesity market 

because of the high hurdles, and 

there have been some failures,” Behan 

said. “There’s been caution in that 

area, which is why we set the bars very 

high to make sure we got robust” efficacy 

and safety profiles. 

Arena also is hoping that lorcaserin’s 

composition also might give it a leg up 

in the partnering race, since both 

Vivus’ Qnexa and Orexigen’s Contrave 

are combinations of generic drugs. 

Qnexa combines phentermine and 

topiramate, while Contrave is a fixed 

dose of bupropion and naltrexone. 

Besides the safety and efficacy, lorcaserin 

also comes with a new mechanism 

and a portfolio of compositionof-matter 

patents. “We believe a partner 

will appreciate that package,” 

Behan said. 

Orexigen, of San Diego, has said it 

plans to build its own sales force for 

the small specialty market in the U.S. 

while it seeks a partner for the primary 

care market and ex-U.S. territories. 

And after reporting positive data from 

the last of its trials, Mountain View, 

Calif.-based Vivus also moved into fullfledged 

partnering mode. 

Arena Prices $52M Public Offering 

Three weeks after nailing down a 

$100 million loan to shore up its 

finances, Arena Pharmaceuticals 

priced a $52.1 million public offering 

in July 2009 to keep it moving toward 

a new drug application for its obesity 

drug lorcaserin, but which also raised 

concerns about dilution. The San 

Diego-based company offered 12.5 

million shares at $4.17 per share, 50 

cents lower than its close on July 7, 

2009. The offering sent its shares 

(NASDAQ:ARNA) down 71 cents, or 

15.2 percent, to close at $3.96. 

The announcement came on a day 

that saw biotechs and their specialty 

pharma cousins announce news of 

more than $180 million in financings. 

But for Arena it was the third recent 

deep drink, following a $100 million 

funding agreement with Deerfield 

Management, its largest shareholder, 

in June 2009, and a $50 million equity 

financing commitment from 

Azimuth Opportunity Ltd. in March 

2009. The Deerfield deal saw Arena

pay Deerfield a 2.25 percent transaction 

fee plus 7.75 percent interest on 

the outstanding principal. When the 

public offering was announced, only 

$15 million of the Azimuth commitment 

had been used. 

Cory Kasimov, an analyst with J.P. 

Morgan, wrote in a research note that 

announcement of the public offering 

was “initially perplexing” given the 

Deerfield loan and the Azimuth drawdown. 

But he said Arena’s revelation 

that it had only $40 million in cash as 

of June 30, 2009, highlighted “the 

increasingly difficult financial situation 

Arena was facing.” The new infusion 

solved the near-term cash problems, 

Kasimov said, but left the company 

and investors dealing with dilution. 

Based on new shares sold since the 

end of the first quarter 2009, Arena 

“has diluted its shareholder base by 

25 percent at a minimum,” he 

wrote. “However, assuming shares 

ultimately eclipse the exercise price of 

$5.42 (and we believe investor’s 

wouldn’t be participating if they didn’t 

believe that shares could climb to 

this level), dilution could actually hit 

70 percent.” 

The payoff could be lorcaserin, a 5- 

HT2c serotonin receptor agonist. Data 

from a nonpivotal Phase III trial could 

come around September 2010. 

However, Arena submitted its new 

drug application for lorcaserin in 

December 2009. Kasimov noted that 

he was “increasingly comfortable with 

lorcaserin’s safety profile following the 

BLOOM data release at the American 

Diabetes Association meeting. 

Arena Gets $100M Loan as 

Lorcaserin Deal Talks Continued 

In June 2009, Arena Pharmaceuticals 

obtained a $100 million credit facility 

from its largest shareholder, 

Deerfield Management, providing 

much-needed funding to propel obesity 

drug lorcaserin through FDA 

review and add muscle to ongoing 

partnership discussions. The money 

didn’t come cheap: Arena will pay 

Deerfield a 2.25 percent transaction 

fee on the loan as well as 7.75 percent 

interest on the outstanding principal, 

which must be repaid over the 

next four years. Additionally, Arena 

issued Deerfield warrants for 28 million 

shares of common stock with an 

exercise price of $5.42 per share. 

Assuming Arena’s stock goes above 

$5.42 and Deerfield exercises those 

warrants, Arena stands to get an 

additional $150 million or more in 

cash, which it could use to repay the 

loan. 

Adam Cutler, an analyst with 

Canaccord Adams Inc., said the deal is 

potentially “quite dilutive” for Arena. 

Yet the company needed the money. 

Arena had just $70.3 million in cash, 

equivalents and short-term investments 

as of March 31, 2009, after 

posting a net loss of $50.6 million during 

the quarter. Despite a $50 million 

equity financing commitment from 

Azimuth Opportunity Ltd., analysts 

predicted Arena’s coffers would run 

dry by the end of that year. 

So it was a “foregone conclusion” 

that whatever Arena did to raise 

money at that point was going to be 

dilutive, Cutler said. But at least by 

signing such a hefty deal with 

Deerfield, Arena “ripped off the Band- 

Aid” in one fell swoop and got 

enough money to finish its pivotal trials, 

submit lorcaserin to the FDA and 

possibly even reach the approval date, 

he told BioWorld. 

Cutler added that the deal is “great” 

for Deerfield, which stands to make a 

nice profit off the warrants if all goes 

well for Arena but will get its loan 

repaid regardless. Deerfield also has a 

two-year option to provide Arena with 

another $20 million in exchange for 

up to 5.6 million warrants at the same 

terms – a no-brainer if the stock beats 

$5.42 within the next two years. Piper 

Jaffray & Co. served as the placement 

agent on the transaction. 

Arena Announces Workforce 

Reduction 

Arena Pharmaceuticals tightened its 

belt a lot during 2009 to make sure it 

would get lorcaserin across the finish 

line. In April 2009, Arena said it would 

reduce its work force by 31 percent, or 

about 130 employees, by June 22, citing 

the “challenging economic environment” 

and the need to reduce its 

cash usage to get through the filing of 

a new drug application for lorcaserin 

in obesity. As a result, the company 

expected to incur cash charges, primarily 

that quarter, of about $3 million, 

but annual operating cost savings 

were expected to be about $25 million. 

Analyst Jonas Alsenas, of Leerink 

Swann & Co., wrote in a research note 

that the move was a “necessary step 

to manage sparse cash resources until 

a partnership deal for lorcaserin can be 

signed.” Robert Hoffman, vice president 

of finance and chief financial officer 

at Arena, said the company was 

“working diligently toward a partnership” 

for its lead drug. 

Arena Hits Endpoints in Phase III 

Obesity Trial, but Stock Drops 

Arena Pharmaceuticals’ first Phase III 

trial of obesity drug lorcaserin met all 

three of its co-primary endpoints, yet 

the company’s shares fell 28 percent in 

March 2009 as investors questioned 

whether the data would be strong 

enough to secure a partnership and 

relieve Arena’s cash concerns. Top-line 

data from the intent-to-treat population 

of the 3,182-patient BLOOM trial 

showed that lorcaserin patients lost an 

average of 12.7 pounds, or 5.8 percent 

of their body weight, while placebo 

patients lost an average of 4.7 

pounds, or 2.2 percent. 

The difference between the two 

groups – 3.6 percent – fell short of the 

5 percent goal outlined in the FDA’s 

guidelines for obesity drug development. 

Yet Arena did meet the other 

half of the FDA’s guidelines, which call 

for the proportion of patients who 

lose 5 percent of their weight on drug 


44 

to be roughly double that on placebo. 

In the BLOOM trial, 47.5 percent of 

lorcaserin patients lost more than 5 

percent of their weight, compared to 

20.3 percent of placebo patients. 

Additionally, 22.6 percent of lorcaserin 

patients lost more than 10 percent of 

their weight, compared to 7.7 percent 

of placebo patients. 

David Walsey, senior director of corporate 

communications at San Diegobased 

Arena, emphasized that obesity 

drugs need to meet just one of the 

two FDA guidelines, which lorcaserin 

did. He added that the co-primary 

endpoints of the trial were the 5 percent 

and 10 percent proportions as 

well as the amount of weight lost at 

one year. The trial met all three with 

highly statistical significance (p < 

0.0001) despite missing the FDA’s 5 

percent goal for placebo-adjusted 

weight loss, he told BioWorld. 

Additionally, lorcaserin was well tolerated 

and met its primary safety endpoint 

of no significant difference in 

the rate of valvulopathy at one year. 

Valvulopathy, or hardening of the 

heart valve, posed a problem for the 

infamous diet drug Phen-Fen (dexfenfluramine-fenfluramine), 

which was 

pulled from the market. Like 

lorcaserin, Phen-Fen agonized the 5- 

HT2c serotonin receptor, but its issues 

were a result of off-target 5-HT2b activation, 

which lorcaserin’s specificity 

appears to avoid. Yet investors were 

unimpressed, pushing the stock down 

$1.27 to close at $3.23. 

Analyst Jonas Alsenas, of Leerink 

Swann & Co., called the selloff in the 

stock “overdone,” writing in a 

research note that the data were 

“consistent with our long-held expectations 

of good but not exceptional 

weight loss with a strong safety and 

tolerability profile.” 

Analyst Adam Cutler, of Canaccord 

Adams Inc., said it is hard to make 

comparisons between lorcaserin and 


other obesity drugs because the trials 

are not “apples to apples.” He also 

noted that the drugs should not necessarily 

be viewed as competitive, 

since the obesity market is certainly 

large enough to support multiple players. 

That said, Cutler called the Arena 

data “underwhelming” compared to 

Orexigen’s Contrave and Vivus Inc.’s 

Qnexa, and said at the time that 

Contrave likely had the best chance of 

FDA approval due to its strong safety 

package. 

Arena Reports Phase IIb Lorcaserin 

Data 

Arena Pharmaceuticals published the 

results from its Phase IIb trial of lorcaserin 

for the treatment of obesity in 

the Dec. 4, 2008, issue of Obesity. The 

randomized, double-blind, placebocontrolled 

study evaluated the efficacy 

and safety of three doses of lorcaserin 

over a 12-week period in nondiabetic, 

obese patients. Compared to placebo, 

patients receiving lorcaserin experienced 

statistically significant greater 

weight loss. Improvements in other 

endpoints, including decreases in cholesterol 

and waist circumference. 

Vivus – Qnexa 

Vivus Inc.’s stock-powering Phase III 

news in September 2009 from the 

EQUIP and CONQUER obesity trials 

could equip the company’s Qnexa to 

conquer not only the pharmaceutical 

market but to pull patients away from 

gastric bypass surgery. Now Mountain 

View, Calif.-based Vivus is hitting the 

partnering trail with Qnexa (phentermine/topiramate 

CR) – and the game 

has changed plenty. 

There’s little debate about Qnexa’s 

potential, thanks to Vivus’ recent 

data. Qnexa delivered placebo-adjusted 

weight loss numbers as high as 9.4 

percent in EQUIP and 8.6 percent in 

CONQUER for the full dose. In the 60 

percent of patients who stayed on the 

drug for a year, the mean placebo 

adjusted weight loss reached 12.2 

percent. 

Aside from efficacy, Qnexa has a few 

other commercial factors in its favor. 

Mid-dose and low-dose versions of the 

drug also performed well in the trials, 

and Vivus CEO Leland Wilson said the 

company plans to pursue approval for 

all three. That resonated with Michelle 

Look, a lead investigator in the studies 

and a physician at the San Diego Sports 

Medicine and Family Health Center. 

Look said during a conference call that 

she liked the idea of having dosing flexibility. 

Qnexa also demonstrated a significant 

impact on comorbidities associated 

with obesity, including blood pressure, 

triglycerides and hemoglobin A1c 

levels. That makes the drug attractive 

not only to primary care doctors but to 

cardiologists and other specialists. 

Analyst Michael King, with Merriman 

Curhan Ford, wrote in a research note 

that Qnexa has the potential to become 

not only the gold-standard obesity 

medicine, but even replace the odious 

but often-resorted-to Roux-en-Y gastric 

bypass procedure. Roux-en-Y involves 

restricting the size of the stomach and 

can result in weight loss of 66 percent 

or more over five years. Hospital stays 

have been reduced thanks to the 

laparoscopic approach, but there’s still a 

risk of surgical complications (including 

death, rarely) and resultant complications 

such as nutrient deficiencies. 

One factor that may complicate Qnexa’s 

commercial potential is the fact that the 

drug combines two generic components: 

the diet drug phentermine and 

the epilepsy drug topiramate. Some 

experts have cautioned that could cap 

its pricing potential, leading to a demise 

along the lines of NitroMed Inc.’s heart 

failure drug BiDil. NitroMed’s combination 

of the generic drugs isosorbide dinitrate 

and hydralazine hydrocholoride 

fizzled when doctors realized they could 

save money by just using the generic 

components. 

But Wilson has plenty of reasons why 

that won’t happen to Qnexa. First, 

Qnexa uses very low doses of its gener-

ic components – as low as one-sixteenth 

of a pill. That’s a bit more complicated 

than just cutting a pill in half, 

Wilson said. Second, Qnexa requires 

titration, which means the dose 

changes frequently over the first week 

– a headache to recreate if you don’t 

have Qnexa’s titration kit. Third, Wilson 

continued, there’s “no way” doctors 

are going to mess with combining obesity 

drugs that aren’t FDA approved 

after the debacle surrounding combo 

drug Fen-Phen. When you put it all 

together, there are “a couple real 

pieces of magic that go on here,” 

Wilson said. 

Vivus Files NDA for Qnexa 

On December 29, 2009, Vivus filed a 

new drug application for obesity drug 

Qnexa in patients who are obese or 

overweight with co-morbidities such 

as hypertension, Type II diabetes, dyslipidemia 

or central adiposity. Qnexa 

combines the generic diet drug phentermine 

with epilepsy drug 

topiramate. The submission is based 

on Phase III data in which Qnexa 

achieved significant percent and categorical 

weight loss compared to placebo 

and met regulatory requirements 

for weight loss products as defined by 

the current FDA guidance. The drug 

remained unpartnered at the time of 

the filing, and a PDUFA date was 

established for late October 2010. 

Vivus president and CEO Leland Wilson 

predicted that the FDA will convene an 

advisory panel for Qnexa, considering 

the safety issues that have plagued 

other obesity drugs. Wyeth’s Fen-Phen 

(dexfenfluramine/phentermine) was 

pulled from the market for safety reasons, 

while a negative advisory committee 

meeting blocked Sanofi-Aventis 

Group’s Acomplia (rimonabant) from 

U.S. approval. 

It will be interesting to see whether 

the FDA convenes a single advisory 

panel or multiple panels to review 

Qnexa, Orexigen Therapeutics Inc.’s 

obesity drug Contrave (bupropion 

SR/naltrexone SR) and Arena 

Pharmaceuticals Inc.’s obesity drug lorcaserin. 

Arena submitted its NDA for 

lorcaserin on Dec. 22, 2009, and 

Orexigen followed shortly after. At the 

time of the Qnexa filing, the only 

meeting of the Endocrinologic and 

Metabolic Drugs Advisory Committee 

listed on the FDA’s tentative 2010 

schedule is May 26-27. 

Vivus Fattens Qnexa Appeal with 

Phase II Sleep Apnea Data 

A week after filing a new drug application 

for Qnexa in obesity, Vivus presented 

Phase II data showing the drug 

also relieved obstructive sleep apnea. 

JMP Securities analyst Jason Butler 

wrote in a research note that the news 

was an “incremental positive” for 

Vivus. While the sleep apnea data may 

strengthen Qnexa’s label, the new 

indication doesn’t meaningfully 

increase the obesity drug’s market 

potential, since many sleep apnea 

patients are obese and thus already 

would be candidates for the drug. In 

fact, the overlap between obesity and 

sleep apnea patients explained why 

Qnexa worked in both indications. 

Obese patients may have excess fat in 

the tissues of their soft palate that 

decreases air flow, or they may have 

abdominal fat pushing up on the lungs 

and air passages, Vivus president and 

CEO Leland Wilson told BioWorld. The 

link between obesity and sleep apnea 

is well established, but Wilson believes 

Qnexa has an additional “weight independent” 

mechanism of action that 

has yet to be elucidated. In the study, 

patients receiving Qnexa achieved a 

rapid improvement in sleep apnea, 

even before they began to show substantial 

weight loss, Wilson said. 

The randomized, double-blind, placebo-controlled, 

parallel-group study 

enrolled 45 obese patients at a single 

clinical trial site. Qnexa patients 

achieved a statistically significant 69 

percent reduction in apnea events per 

hour of sleep, dropping from 46 to 14 

events while placebo patients dropped 

from 44 to 27 events (p < 0.001). 

Additionally, Qnexa patients lost 10.2 

percent of their body weight compared 

to 4.3 percent for the placebo group. 

Qnexa patients also reduced their systolic 

blood pressure and improved their 

oxygen saturation. There were no serious 

adverse events, and the most common 

side effects were dry mouth, 

altered taste and sinus infection. 

Percentage of Patients with Obstructive Sleep Apnea 

Type II 

diabetes 

Obesity 

Congestive 

heart failure 

Drug-resistant 

hypertension 

72% 

77% 

80% 

80% 

Source: Vivus Inc., citing Einhorn et al., Endocrine Prac 2007; O’Keefe and Patterson, 

Obesity Surgery 2004; Maisel et al., HFSA 2007, Wash DC; and Logan et al., J. 

Hypertension 2001. 


46 

Butler wrote that he was “specifically 

impressed” with the blood pressure 

improvement, which was similar to 

that seen in Qnexa’s previous Phase III 

obesity trials. Yet he noted that he 

wouldn’t focus too much on the 

weight loss numbers, considering that 

it was a small, single-site trial. 

Wilson agreed that while the study 

was large from a sleep apnea standpoint, 

it was small from an obesity 

standpoint. However, he contended 

the new efficacy data, combined with 

Vivus’ wealth of safety data from its 

large obesity trials, provide a framework 

for talking to the FDA about a 

path to approval in sleep apnea. 

Wilson noted that there are currently 

no approved drugs for obstructive 

sleep apnea. 

Vivus Raises $95M in Stock Sale 

Ahead of Expected Partner Talks 

Vivus will have a strengthened hand 

heading into any partner talks on 

Qnexa after it announced plans in 

September 2009 to raise $94.5 million 

through a public offering of stock. 

Vivus would be going into partner discussions 

with $250 million, including 

the $94.5 million equity financing, 

enough to last through the regulatory 

filing and approval process, estimated 

Jason Butler, an analyst with JMP 

Securities. Vivus’ offering of 9 million 

shares was priced at $10.50 per share 

and was expected to close around 

Sept. 23. J.P. Morgan Securities Inc. is 

acting as sole book-running manager 

of Vivus’ stock offering. JMP Securities 

LLC, Lazard Capital Markets LLC and 

Merriman Curhan Ford are acting as 

co-managers of the offering. Trout 

Capital LLC acted as an advisor to the 

company. 

Phase III Efficacy Results Could 

Give Vivus a Partnering Edge 

Besides loads of cash, another factor 

that could give Vivus an edge at the 

negotiating table is its Phase III efficacy 

results for Qnexa, data that appear 

to outshine the other two leading con- 


tenders, lorcaserin from Arena 

Pharmaceuticals Inc. and Contrave 

from Orexigen Therapeutics Inc. 

Looking across the respective trials, 

the mean placebo-adjusted weight 

loss was 9.4 percent for Vivus’ Qnexa, 

5 percent for Contrave and 3.5 percent 

for lorcaserin, according figures 

from Jason Butler, an analyst with JMP 

Securities. Leerink Swann analyst 

Steve Yoo agreed that Qnexa has “the 

best efficacy of the three drugs.” But 

Yoo said the issue at hand for Qnexa is 

its safety profile. Although he noted 

that the Phase III safety data looked 

better than he expected in terms of 

suicide ideation and cognitive adverse 

events, common side effects were dry 

mouth and tingling in the fingers and 

toes. With Orexigen’s product, nausea 

was a common side effect in study 

patients while headache was a common 

side effect with Arena’s drug. But 

there is probably room in the marketplace 

for all three products, both analysts 

said. “Physicians don’t have 

options now, and they want as many 

as they can,” Butler said. 

The analysts cautioned that partnership 

talks are likely to be complex and possibly 

drawn out, given the number of 

sellers and buyers and the multiple factors 

to be considered for each product. 

Butler said it could be mid-2010 

before a partner emerges for Vivus, 

and Yoo agreed that the talks could 

take a while. Potential suitors will need 

time to sort out all the data from the 

three companies, and when it comes 

time to deal, they could play one of 

the obesity companies off the other to 

get better terms, Yoo said. “I think all 

three of these drugs will generate 

partnership interest,” he said. 

Vivus may be attractive for its weight 

loss results, while lorcaserin may get a 

second look for its safety profile and possibly 

its patent estate. Both Vivus and 

Orexigen have products that have raised 

the possibility of generic substitution. 

Vivus Reveals Data for Weight Loss 

in Diabetes Patients 

In October 2009, Vivus revealed the 

weight loss effects of Qnexa in subjects 

with Type II diabetes. Subjects treated 

with Qnexa for 28 weeks had a mean 

weight loss of approximately 17 

pounds or 8 percent of their starting 

body weight, compared to 2.9 pounds 

or 1.2 percent (p < 0.0001) for subjects 

treated with placebo. In the study, 61 

percent of the patients treated with 

Qnexa had weight loss of 5 percent as 

compared to 14 percent of the patients 

in the placebo group (p < 0.0001). 

Data were revealed at the Obesity 

Society Annual Scientific Meeting in 

Phoenix. Some data from the trial 

were released earlier in 2009. 

Vivus Wows Investors with Phase 

III Qnexa Data 

Vivus wowed analysts and investors in 

September 2009 with better-thanexpected 

data from its final two Phase 

III trials of obesity drug Qnexa. The 

company’s shares (NASDAQ:VVUS) 

reached heights not seen in a decade, 

jumping $4.89, or 71 percent, to close 

at $11.80. J.P. Morgan analyst Cory 

Kasimov wrote in a research note that 

the data “exceeded our already high 

expectations and significantly differentiated 

Qnexa from the competition.” 

The FDA requires new obesity drugs to 

show either 5 percent placebo-adjusted 

weight loss or twice as many 

patients losing 5 percent of their 

weight on drug vs. placebo. Vivus’s 

first Phase III trial of Qnexa, which 

combines the generic diet drug phentermine 

with epilepsy drug 

topiramate, hit both of the FDA’s 

goals. 

The company’s second Phase III trial, 

dubbed EQUIP, tested low-dose and 

full-dose versions of Qnexa in 1,267 

morbidly obese patients. Placeboadjusted 

weight loss was 9.4 percent 

(31 pounds) at the full dose and 3.5 

percent (12 pounds) at the low dose. 

Although the low dose missed the

FDA’s first goal, both doses hit the second 

goal, with 67 percent of full-dose 

Qnexa patients and 45 percent of lowdose 

Qnexa patients vs. 17 percent of 

placebo patients losing at least 5 percent 

of their weight. 

Vivus’s third Phase III trial, CONQUER, 

enrolled 2,487 overweight and obese 

patients with high blood pressure, 

high cholesterol or Type II diabetes. 

Placebo-adjusted weight loss was 8.6 

percent (24 pounds) at the full dose 

and 6.6 percent (18 pounds) for 

patients receiving a middle dose of 

Qnexa. Seventy percent of full-dose 

Qnexa patients and 62 percent of middose 

Qnexa patients vs. 21 percent of 

placebo patients lost at least 5 percent 

of their weight. Additionally, a subset 

analysis of high-risk patients showed 

statistically significant improvements 

in blood pressure, triglycerides and 

hemoglobin A1c levels. 

Across both studies, quality of life 

improved for patients on Qnexa, and 

there were no side effect surprises – 

even after specific analyses of suicidality 

and depression. The most common 

side effects were dry mouth and tingling, 

and additional QT prolongation 

and cognitive/psychomotor testing 

came up clean. Kasimov noted that 

“despite the obvious limitations of 

comparing different drugs across different 

trials, these results nevertheless 

stack up quite favorably” against 

Contrave and lorcaserin. 

Orexigen recently wrapped up its pivotal 

program for Contrave, which 

combines the opioid blocker naltrexone 

with the dopamine stimulator 

bupropion. Placebo-adjusted weight 

loss ranged from 4.2 percent to 5.2 

percent across the trials, and the most 

common side effects were nausea, 

constipation and headache. 

Analysts have said there’s room in the 

market for all three obesity drugs – but 

they’ll need big pharma marketing 

muscle to reach those primary care 

prescribers, and as of early 2010 all 

three drugs remained unpartnered. In 

Vivus’ case, president and CEO Leland 

Wilson said that’s been a matter of 

choice. Despite “strong interest,” 

Vivus opted to put off partnering 

negotiations until it had all of its Phase 

III data in hand, Wilson told BioWorld. 

“We had such a strong belief that the 

data would be this good – we knew 

we could derive maximum value at the 

end of Phase III,” Wilson said. 

With the Phase III program complete, 

Vivus is actively looking for a partner 

that can handle global sales both to 

primary care doctors and to cardiologists 

and other specialists that may be 

interested in Qnexa’s effects on comorbidities 

associated with obesity. Having 

one partner to do it all will help ensure 

uniform branding and control of parallel 

imports, Wilson said. 

Vivus Hits Endpoints in Phase III, 

Offers Assurance on Patents 

The first of three Phase III trials with 

Vivus’ obesity drug Qnexa met its endpoints 

in December 2008, demonstrating 

average weight loss of 9.2 percent 

(19.8 pounds) at the full-dose and 8.5 

percent (18.2 pounds) at the mid-dose, 

compared to 1.7 percent (3.3 pounds) 

for the placebo group (p < 0.0001). 

Those results indicated Qnexa may fare 

better than currently available prescription 

weight-loss drugs, like the generic 

drug phentermine, F. Hoffmann-La 

Roche Ltd.’s Xenical (orlistat) and 


monohydrate capsules C-IV). Analyses 

have shown the placebo-adjusted 

weight loss for phentermine at around 

3 percent to 5 percent, Xenical at 2.9 

percent, and Meridia at 4.2 percent. 

The FDA said in a guidance document 

that it wants to see at least a 5 percent 

placebo-adjusted weight loss from 

obesity drugs. All three Qnexa trials 

were conducted under special protocol 

assessments with the FDA. 

The 28-week Phase III trial included 

756 obese patients who were ran- 

domized to one of seven arms: oncedaily 

mid-dose Qnexa (7.5 mg phentermine/46 

mg topiramate CR), oncedaily 

full-dose Qnexa (15 mg phentermine/92 

mg topiramate CR), the 

respective phentermine and topiramate 

constituents, or placebo. In addition 

to beating placebo, Qnexa outperformed 

its generic components. 

There were no serious drug-related 

adverse events in the trial, and the 

most common side effects were paresthesia 

(a prickly skin sensation), dry 

mouth, altered taste and constipation. 

Although many obese patients also 

suffer from depression, both Qnexa 

treatment groups experienced statistically 

significant improvements in 

depression ratings (p < 0.05). The 

trial’s drop-out rate of 29 percent was 

in-line with drop-out rates of 30 percent 

seen with Xenical and 31 percent 

with Meridia. 

In a research note, Leerink Swann & 

Co. analyst Jonas Alsenas called the 

weight loss data “very good” but 

voiced concerns about the paresthesia 

rates as well as a “potentially significant” 

blocking patent held by Johnson 

& Johnson on the use of topiramate in 

obesity. The patent could give J&J 

“significant leverage during licensing 

talks” and make it difficult for Vivus to 

close a deal with another partner, 

Alsenas wrote. 

Yet Vivus Chief Financial Officer 

Timothy Morris said Vivus is “very 

comfortable” with its patent position, 

which includes a patent on the use of 

topiramate and phentermine together 

for obesity. He added that the 46 mg 

topiramate dose used in mid-dose 

Qnexa is below the 50 mg lower limit 

of J&J’s patent. Topiramate is approved 

for epilepsy and for migraine prevention, 

while phentermine is a generic 

diet drug. Qnexa combines them in an 

effort to capture topiramate’s ability to 

increase feelings of fullness and phentermine’s 

ability to decrease appetite 

and increase energy usage. 


48 

Vivus’ Pipeline Gets $65M Boost 

Via Direct Offering 

Vivus padded its coffers with a $65 

million registered direct offering in 

August 2008. The firm agreed to sell 

8.4 million shares of common stock to 

new and existing investors at a price of 

$7.77 each, marking a 7 percent discount 

to Vivus’ previous closing price 

of $8.34. The company said in its 

prospectus that net proceeds were 

expected to total about $63.4 million 

and will add to the $155 million Vivus 

had in the bank, as of June 30, 2008. 

In April 2008, Vivus entered a $30 million 

funding deal with Deerfield 

Management to ensure adequate 

resources to move forward with one of 

those programs, its erectile dysfunction 

drug avanafil. 

Orexigen Therapeutics – Contrave 

Orexigen Therapeutics Inc., of San 

Diego, is developing Contrave (naltrexone 

SR/bupropion SR) for obesity. 

Analysts expect the San Diego-based 

company to file for approval with the 

FDA in early 2010. 

Contrave combines long-acting versions 

of naltrexone, an opioid blocker 

approved for opioid and alcohol 

addiction, and bupropion, a 

dopamine stimulator approved for 

depression and smoking cessation. 

That combination allows Orexigen to 

“target some core issues in obesity,” 

former Orexigen President and CEO 

Gary Tollefson told BioWorld, since 

naltrexone helps modify unhealthy 

eating habits by reducing the perceived 

reward associated with food 

addictions, and bupropion addresses 

both weight loss and depression, a 

frequent comorbidity condition of 

obesity. 

Orexigen President and CEO Michael 

Narachi said during a July 2009 conference 

call that the company plans to 

“get ready for a launch in the specialty 

markets ourselves” and hopes to 

pick up a partner for the primary care 

and ex-U.S. markets. Yet J.P. Morgan 


analyst Cory Kasimov wrote in a 

research note that he “would not be 

surprised if discussions ultimately culminate 

in an outright takeout.” 

Orexigen Reports Contrave Results 

In October 2009, Orexigen reported 

results from new intent-to-treat analyses 

from its COR-I and COR-II Phase III 

trials of Contrave, which showed that 

about 25 percent to 33 percent of 

patients lost 10 percent or more of their 

body weight and 12 percent to 16 percent 

lost at least 15 percent. Obese 

patients on Contrave also demonstrated 

significant improvements in markers 

of cardiometabolic risk, including waist 

circumference, HDL and triglycerides. 

Data were presented at the Obesity 

Society meeting in Washington. Topline 

data from COR-I and COR-II were 

reported in July 2009. 

Orexigen Files Shelf Registration 

In September 2009, Orexigen filed a 

shelf registration statement with the 

SEC under which the company may 

raise up to $150 million through the 

issuance of stock, debt and/or warrants. 

Proceeds will be used for regulatory 

and pre-commercial support of 

obesity drug Contrave (bupropion 

SR/naltrexone SR) as well as clinical trials 

and general corporate purposes. 

With Phase III Obesity Data in Hand, 

Orexigen Prices $75M Offering 

As expected, Orexigen followed its 

release of Phase III Contrave data in 

July 2009 with a financing, garnering 

$75 million through a public offering 

of 10 million shares priced at $7.50 

each. That price represented a discount 

of about 9 percent to Orexigen’s 

previous closing price of $8.27. The 

total amount raised was $81.6 million. 

Leerink Swann LLC acted as sole bookrunning 

manager for the offering, 

with Lazard Capital Markets LLC, 

Canaccord Adams Inc., JMP Securities 

LLC and Natixis Bleichroeder Inc. acting 

as co-managers. Another 1.5 million 

shares were available to cover 

overallotments. 

Net proceeds will help Orexigen in 

more ways than one. The company 

reported $64.7 million in cash, equivalents 

and short-term investments at 

the end of the first quarter of 2009. 

Orexigen revealed in a conference call 

that it had about $45 million as of 

June 30, 2009 – enough for about 

two quarters based on historical burn. 

Although Orexigen’s costs have 

decreased considerably now that its 

large Phase III program for obesity drug 

Contrave is complete, the company still 

has to spend on regulatory and launch 

preparations, not to mention ongoing 

Phase II trials with obesity drug Empatic 

(bupropion SR/zonisamide SR). One 

factor that could decrease costs considerably 

would be the addition of a 

development partner. But at the beginning 

of 2010, all three Phase III obesity 

drugs – Contrave, Arena Pharmaceuticals 

Inc.’s lorcaserin and Vivus Inc.’s Qnexa 

(phentermine/topiramate) – remained 

unpartnered. That said, Orexigen 

President and CEO Michael Narachi 

said in July 2009 that with the full 

Contrave data in hand, Orexigen can 

begin partnering discussions “in 

earnest” – and the new financing will 

allow the company to do so from a 

position of strength. 

Orexigen Clears Phase III Hurdle, 

But Battle of the Bulge Is Not Over 

Orexigen beat competitors Vivus Inc. 

and Arena Pharmaceuticals Inc. across 

the Phase III obesity finish line, reporting 

in July 2009 that Contrave met its 

endpoints in its three remaining pivotal 

studies. The news pushed shares of 

Orexigen (NASDAQ:OREX) up $1.51, 

or 26.5 percent, to close at $7.20. 

The FDA wants obesity drugs to show 

either 5 percent placebo-adjusted 

weight loss or twice as many patients 

losing 5 percent of their weight on 

drug vs. placebo. Orexigen’s story was 

initially complicated, as the company’s 

first Phase III trial of Contrave fell short 

of both FDA goals. Placebo-adjusted 

weight loss was 4.2 percent, and 66

percent of Contrave patients vs. 42 

percent of placebo patients lost more 

than 5 percent of their weight. 

Yet that trial included an intensive 

behavior modification program, resulting 

in a high placebo hurdle to overcome. 

Not so with the COR-I (NB-301), 

COR-II (NB-303) and COR-Diabetes 

(NB-304) studies, all of which met the 

FDA’s second parameter. The three 

randomized, double-blind, placebocontrolled, 

56-week Phase III trials 

enrolled more than 3,700 patients. All 

three trials included a typical diet and 

exercise regimen. 

In COR-1, placebo-adjusted weight 

loss was 4.8 percent (6.1 percent/13.3 

pounds for Contrave vs. 1.3 percent/3 

pounds for placebo). Yet the percent 

of patients to lose more than 5 percent 

of their weight was 48 percent 

for Contrave and 39.5 percent for a 

low-dose formulation, both more than 

double the 16.4 percent for placebo. 

In COR-II, placebo-adjusted weight 

loss was 5.2 percent (6.4 percent/13.8 

pounds for Contrave vs. 1.2 percent/2.8 

pounds for placebo) – hitting 

the first FDA target. COR-II also 

achieved the second FDA target: 56.3 

percent of Contrave patients lost more 

than 5 percent of their weight, compared 

to 17.1 percent for placebo 

patients. A high-dose Contrave arm 

designed for nonresponders did not 

show significant differences from the 

regular dose. 

COR-Diabetes, which compared 

Contrave to placebo in Type II diabetes 

patients, showed that 44.5 percent of 

Contrave patients vs. 18.9 percent of 

placebo patients lost more than 5 percent 

of their weight. Contrave patients 

also showed a significant 0.6 percent 

reduction in HbA1c levels, compared 

to a 0.1 percent reduction for placebo. 

The Phase III Contrave program also 

showed statistically significant improvements 

in several secondary endpoints, 

including quality of life. Overall, the 

drug was well tolerated, with nausea, 

constipation and headache emerging 

as the most common side effects, 

although there were also seven serious 

adverse events. Just over half of 

patients completed the trial for both 

the drug and placebo groups. 

Orexigen Appoints New CEO 

Orexigen’s board appointed a new CEO 

and president in April 2009. Michael 

Narachi previously served as CEO of privately 

held Ren Pharmaceuticals Inc. 

Narachi succeeds Executive Chairman 

Eckard Weber, who took over as interim 

president and CEO after former top 

executive, Gary Tollefson, resigned due 

to health reasons in late 2008. 

Orexigen Sinks Despite Contrave 

Efficacy in Phase III Obesity Trial 

Orexigen’s Contrave hit its endpoints 

in the first of four Phase III studies, but 

concerns that the data missed the 

FDA’s benchmark for efficacy in obesity 

sent shares of the San Diego-based 

company falling 15.7 percent in 

January 2009. Data from the NB-302 

study, which involved 793 obese 

patients participating in an intensive 

diet and exercise behavior modification 

program, showed that those 

treated with Contrave, a combination 

of sustained-release versions of naltrexone 

and buproprion, showed a significant 

reduction in body weight, 

meeting co-primary endpoints. Data 

from the intent-to-treat population 

demonstrated an average weight loss 

of 20.3 pounds, or 9.3 percent of 

patients’ baseline body weight, vs. 11 

pounds, or 5.1 percent, in the placebo 

arm. The completer analyses showed 

an even greater reduction, with 

Contrave-treated patients losing an 

average of 25 pounds, of 11.5 percent 

of their baseline body weight, compared 

to 16 pounds, or 7.3 percent, 

on placebo. 

About 66 percent of patients receiving 

Contrave lost at least 5 percent of 

their total body weight vs. 42 percent 

of patients on placebo. Those results 

should have been good news for the 

Orexigen – the company and many 

analysts hailed the study’s outcome as 

positive – but investors clearly worried 

that the FDA’s 2007 guidelines for 

obesity drug development could hamper 

the drug’s chances for approval. 

According to those guidelines, the difference 

in weight loss between drug 

and placebo should be at least 5 percent, 

and Contrave’s difference to 

placebo was 4.1 percent. 

Guidelines also look for twice the number 

of patients in the treatment group 

compared to placebo to achieve weight 

loss of greater than 5 percent of their 

baseline body weight. By that requirement, 

Contrave fell short again, though 

Orexigen pointed out that the percentage 

of patients on Contrave to lose at 

least 10 percent of their baseline body 

weight was double that of the placebo 

arm, 41.5 percent vs. 20.2 percent. 

But the company maintained that 

those guidelines are not binding, and 

Chief Financial Officer Graham Cooper 

added that they do not take into 

account the intense diet and exercise 

regimen of patients. “This trial is a little 

different from the standard [obesity] 

trial, which has minimum placebo 

intervention,” he told investors during 

a conference call. In the NB-302 study, 

all patients underwent the behavior 

modification therapy. 

In addition to the weight loss, results 

showed that Contrave resulted in 

improved markers associated with cardiovascular 

disease in obese patients. 

The most common adverse event associated 

with treatment was nausea, 

which accounted for much of the 25.9 

percent discontinuation rate in the 

study. “Overall, we’re pleased with the 

results of this trial on a number of 

fronts,” said Eduardo Dunayevich, 

Orexigen’s chief medical officer. 

Analyst Phil Nadeau, of Cowen and 

Co., wrote in a research note that 


50 

while “investors are likely to debate 

whether the weight loss data surpass 

the FDA’s bar” for clinical significance, 

“we think Orexigen makes a 

good case that the data do,” meaning 

that the FDA likely would accept 

the NB-302 study as one of the two 

positive Phase III studies needed for 

approval. 

Orexigen Presents Phase I and III 

Contrave Data 

At the Obesity Society Annual Scientific 

Meeting in October 2008, Orexigen presented 

data from its two Phase I trials 

and primary analysis of its four ongoing 

Phase III trials. The primary objective 

of the Phase I Contrave development 

program was to improve tolerability 

by slowing the rate at which naltrexone 

dissolves, slowing its entry into 

the bloodstream (Tmax) and reducing 

the peak concentration it achieves in 

the blood (Cmax). The Phase I data 

showed that Contrave successfully 

achieved key objectives. Analysis from 

the ongoing Phase III trials supported 

that the naltrexone SR formulation 

improvements are associated with tolerability 

advantages. 

At ADA, Orexigen Reports on Phase 

IIb Data Review 

At the June 2008 American Diabetes 

Association meeting, Orexigen said a 

review of data from a Phase IIb trial 

showed that patients assigned to 

Contrave dosage groups demonstrated 

a 50 percent reduction in the 

prevalence of metabolic syndrome, a 

group of risk factors associated with 

obesity that may increase the risk of 

developing diabetes or cardiovascular 

disease. A retrospective evaluation on 

the baseline prevalence of metabolic 

syndrome revealed that among 

Contrave patients who completed 24 

weeks of treatment, the percentage 

of subjects with metabolic syndrome 

decreased from 31 percent to 15 percent. 

Among patients on placebo, the 

prevalence of metabolic syndrome 

decreased by a smaller percentage, 

from 38 percent to 30 percent. 


Orexigen Prices $77M Follow-On 

Orexigen Therapeutics padded its balance 

sheet with a $77 million public 

stock offering in January 2008. The 

company offered 7 million shares 

priced at $11 each, plus an additional 

1.05 million shares to cover any overallotments. 

Novo Nordisk – Victoza 

Victoza (liraglutide) as an anti-obesity 

agent in obese, non-diabetic people is 

in Phase III development by 

Copenhagen, Denmark-based Novo 

Nordisk A/S. The drug is a once-daily 

glucagon-like peptide-1 analogue. 

Victoza Approved for Type II Diabetes 

In January 2010, Victoza was approved 

by the FDA for Type II diabetes. 

Victoza’s labeling carries a black-box 

warning that highlights the risk of thyroid 

C-cell tumors. Piper Jaffray analyst 

Sam Fazeli called the boxed warning a 

“worst case” outcome for Victoza, 

essentially leaving Byetta as the “first 

choice,” despite that drug’s twice-daily 

injection routine and higher incidence 

of nausea and vomiting. 

At a meeting of the FDA’s Endocrinologic 

and Metabolic Drugs Advisory 

Committee in April 2009, regulators 

raised concerns over data from other 

investigational long-acting GLP-1s that 

suggested the C-cell tumor results were 

likely a class effect. The panel at the previous 

April’s meeting had voted 6 to 6, 

with one abstention, that thyroid C-cell 

tumors in animal studies of Victoza 

should preclude the drug’s approval for 

Type II diabetes. While it is not known if 

Victoza could cause thyroid cancer in 

humans, including medullary thyroid 

carcinoma, a rare form of the disease, 

the labeling restricts the drug against 

use as a first-line treatment until additional 

studies are completed that support 

expanded use, regulators noted in 

a statement. Victoza’s boxed warning 

also includes a contraindication for 

patients with a personal or family history 

of medullary thyroid carcinoma or in 

patients with multiple endocrine neo- 

plasia syndrome type 2. Alan Moses, 

chief global medical officer at Novo, 

noted that the risk of medullary thyroid 

carcinoma “represents a very, very small 

percentage of the population. 

Also in January 2010, Novo Nordisk 

received approval for Victoza in Japan 

for the treatment of Type II diabetes. 

Novo Nordisk said it expected to launch 

Victoza in Japan in the first half of 2010 

upon completion of price negotiations. 

Alizyme – cetilistat 

Cetilistat (ATL-962) is in development in 

Japan for obesity. In December 2008, 

Alizyme plc, of Cambridge, UK, said its 

partner Takeda Pharmaceutical Co. 

Ltd., of Osaka, Japan, commenced a 

Phase III study of cetilistat for the treatment 

of obesity. In September 2008, 

Alizyme announced that it was to 

receive a milestone payment of $3 million 

following the decision by Takeda to 

commence the Phase III. A spokeswoman 

for Alizyme said data from the 

Japanese development program have 

been very positive to date. Even if the 

product is approved only in Japan that 

would bring in significant revenues. 

“This is the crown jewel, and every 

effort will be put in to keep [cetilistat] 

alive,” she said. 

In August 2003, Alizyme entered its 

first license deal, granting rights to its 

anti-obesity treatment ATL-962 to 

Takeda Chemical Industries, Japan’s 

largest pharmaceutical company, in a 

$42 million deal. Alizyme received $2 

million up front, with the rest payable 

in milestones. The deal gave 

Cambridge-based Alizyme double-digit 

royalties on future sales in Japan, with 

all Japanese development costs being 

paid by Takeda. 

Tim McCarthy, Alizyme finance director, 

told BioWorld, “I don’t think we could 

get a better partner for Japan. Even if 

we did a global deal with a major pharmaceutical 

company the Japanese market 

would be secondary, and I don’t 

think anyone else could develop the

Japanese market as well as Takeda.” 

Takeda is “devoting a lot of resource to 

this; it is an important product in their 

portfolio,” said McCarthy. McCarthy 

said Alizyme decided to agree to a 

license in Japan in advance of the Phase 

IIb results after an approach from 

Takeda. “They were keen to acquire 

rights ahead of a Phase II auction. We 

were being courted by the No. 1 

Japanese company, and we have sorted 

out a good deal that will not have any 

impact on the value of other licenses.” 

In the Phase Ib trial, cetilistat showed 

similar efficacy to orlistat, the active 

ingredient of F. Hoffmann-La Roche 

Ltd.’s anti-obesity treatment Xenical. 

In September 2009, Alizyme said it was 

progressing on the sale of cetilistat, 

which is its main asset. The drug went 

on the market after the company went 

into receivership in July 2009. The 

receivers said a number of offers were 

made, and the transaction was being 

completed with the preferred bidder. 

Amylin Pharmaceuticals – 

pramlintide and metreleptin 

In 2009, San Diego-based Amylin 

Pharmaceuticals Inc. announced positive 

top-line Phase II data from a pramlintide/metreleptin 

study. The combination 

of pramlintide, an analogue of the 

natural hormone amylin, and recombinant 

human leptin (r-metHuLeptin; 

metreleptin) is in development for the 

treatment of obesity 

Early Stage Obesity Deal Nets 

Amylin $1.075B from Takeda 

Amylin got a double dose of good 

news in November 2009, signing a $1 

billion-plus deal to co-develop obesity 

compounds with Japanese partner 

Takeda Pharmaceutical Co. Ltd., and 

getting FDA approval for expanded use 

of diabetes drug Byetta (exenatide) as a 

first-line therapy. But it was the collaboration 

with Takeda that drew headlines. 

“We’re very excited about this 

deal for several reasons,” Alice Izzo, 

Amylin’s executive director of corporate 

affairs, told BioWorld. “Overall, this collaboration 

allows both companies to 

advance more programs for obesity 

treatments more quickly than either 

company could do alone,” she said. 

Leerink Swann analyst Joshua 

Schimmer stated in a research note 

that the deal monetizes the obesity 

compounds and reduces future expenditures 

as the company works toward 

positive cash flow from operations by 

the end of 2010. He noted that in the 

second quarter of 2009, Amylin spent 

$8.1 million on obesity research and 

development, or about 13 percent of 

its R&D expenditures. Under the deal, 

Amylin will receive $75 million up front 

and could draw more than $1 billion in 

additional payments for achieving 

milestones over the term of the agreement. 

The deal covers Phase II obesity 

compounds pramlintide/metreleptin 

and davalintide in Amylin’s pipeline 

and also includes additional compounds 

from both companies’ obesity 

research programs. 

For its part, Amylin will work to take 

U.S. development of the partnered 

obesity compounds through Phase II, 

while Takeda will be responsible for 

activities beyond that point. The two 

companies will split the costs related to 

obtaining U.S. approval 80-20, with 

Takeda taking on the lion’s share. 

However, Takeda will be 100 percent 

responsible for costs associated with 

obtaining approval outside the U.S. 

Amylin will have the option to co-commercialize 

the first two approved products 

in the U.S. and any follow-on products 

containing the identical active 

ingredients. 

Izzo pointed out that Amylin is an 

expert in peptide and protein science 

and is a diabetes market leader in the 

U.S., and that Takeda is a leader in 

metabolic disease therapeutics. In 

addition, she noted that Takeda provides 

a global reach for the development 

and commercialization of the 

obesity compounds. 

Amylin would appear to be in an enviable 

position with a partnership for its 

midstage obesity program, given that 

late-stage obesity programs at Arena 

Pharmaceuticals Inc., Orexigen 

Therapeutics Inc. and Vivus Inc. remained 

unpartnered into early 2010. But Leerink 

Swann’s Schimmer said the Amylin- 

Takeda partnership “bodes well for” the 

partnership prospects for those three 

firms. 

Amylin Starts Phase IIb in Obesity 

In May 2008, Amylin Pharmaceuticals 

started a Phase IIb study evaluating various 

dosing combinations of pramlintide 

and recombinant human leptin for 

the treatment of obesity. The objective 

of the dose-ranging study was to support 

dose selection for Phase III, and to 

inform the ongoing development of a 

convenient delivery system for the combination 

regimen. The six-month, randomized, 

double-blind, placebo-controlled 

multicenter study enrolled 

approximately 600 overweight and 

obese subjects. 

Obecure – Histalean 

Obecure Ltd., of Ramat Gan, Israel, has 

Histalean in development for several 

anti-obesity indications. It is in Phase II 

for obesity treatment, in a Phase II 

mechanism of action study, and in 

Phase I to mitigate the weight gain side 

effect associated with antipsychotic 

drug Zyprexa (olanzapine, Eli Lilly and 

Co.). Histalean is comprised of betahistine, 

an H1 receptor agonist and partial 

H3 receptor antagonist. 

Obecure Reports Histalean Phase Ib 

Results 

In June 2009, Obecure reported positive 

data from its Phase Ib study of 

Histalean to mitigate the weight gain 

side effect associated with antipsychotic 

drug Zyprexa with preliminary analysis 

showing that the trial achieved its 

primary objective, confirming the safety 

of administering 144 mg/day Histalean 

in combination with olanzapine. Topline 

results also indicated a statistically 

significant reduction in mean weight 


52 

gain due to olanzapine in the Histaleantreatment 

group. 

Histalean Phase IIb Enrollment Is 

Complete 

In January 2009, Obecure completed 

enrollment in its Phase IIb trial, BET-207, 

evaluating the safety and efficacy of 

Histalean for weight loss in obesity. The 

double-blinded, randomized, placebocontrolled, 

dose-ranging study is 

designed to evaluate the drug in about 

180 pre-menopausal obese women. 

The study is intended to confirm and 

extend previous Phase II findings suggesting 

strong gender and age dependence 

and a significant response in 

females, age = 50 years, treated with 48 

mg/day Histalean. The co-primary endpoints 

are the mean percent weight loss 

and the percentage of subjects achieving 

weight loss of 5 percent or more. 

Obecure Starts Histalean Phase II 

Trial 

In September 2008, Obecure started a 

Phase II trial to evaluate the efficacy of 

Histalean in obese patients. The study is 

a follow-up to the company’s post-hoc 

findings in a prior Phase II study, suggesting 

that treatment with a 48mg/day 

dose of the drug provides significant 

weight reduction in obese 

women up to the age of 50. The study 

is to confirm the efficacy of a 12-week 

treatment with the drug in obese but 

otherwise healthy premenopausal 

females ages 18 to 50. 

Preliminary Phase II Histalean 

Results Are Reported 

In August 2007, Obecure reported preliminary 

results from its 281-patient 

Phase II trial of Histalean (formerly 

OBE101) in obesity, and said data suggested 

strong gender and age effects, 

with greatest efficacy in women 50 or 

younger. Subjects in the study were randomized 

into one of four groups to be 

treated with 16 mg, 32 mg or 48 mg of 

Histalean or placebo for a 12-week 

treatment period. Top-line results 

showed no statistically significant difference 

among any of the treatment arms 


vs. placebo; however, a post hoc segmentation 

analysis of female subjects, 

age 50 or younger, in the per-protocol 

cohort demonstrated a substantial difference 

between the mean weight loss 

in the high-dose arm compared to the 

placebo arm. Obecure reported that the 

effect was even more pronounced when 

the analysis was limited to non-Hispanic 

women. At the end of week 12, 12 of 

the 25 women receiving Histalean at the 

48-mg dose lost an average of 2.61 kg 

(2.91 percent of their weight) vs. 23 

women on placebo, who lost 0.4 kg 

(0.43 percent of their weight). 

Orexigen Therapeutics – Empatic 

Behind Contrave (bupropion SR/naltrexone 

SR) in Orexigen Therapeutics Inc.’s 

pipeline is Empatic, which combines 

long-acting versions of bupropion and 

zonisamide, a seizure drug believed to 

modulate sodium channels and enhance 

dopamine and serotonin activity. While 

Contrave is intended to induce sustained 

weight loss, Empatic would be used for 

more intense and rapid weight loss 

needed for severely obese patients. 

Orexigen’s New Empatic Data: Nice 

Obesity-Partner Package 

Orexigen’s Phase IIb data with Empatic 

in October 2009 showed that the combination 

drug for obesity beat Contrave 

(the firm’s other combo drug) in terms 

of weight loss, and opened up a new 

zone of speculation: Will San Diegobased 

Orexigen package the compounds 

together or split them? 

“We’re comfortable enough at this 

point saying that it makes sense for 

both us and a potential partner to 

entertain the idea of an obesity franchise 

deal,” said Dennis Kim, vice president 

of medical affairs and communications 

for Orexigen, at the time. 

Although such an arrangement makes 

strategic sense, he noted, the company 

is open to other options. Empatic contains 

an anti-convulsant not to be used 

by pregnant women, and many of the 

patients who seek obesity therapy are 

childbearing age. 

Empatic’s latest results also helped quell 

worries about regulatory road bumps 

due to rules about synergies with 

combo drugs. The agency’s draft guidance 

says decision makers would more 

likely smile upon combo therapies that 

achieve weight loss twice that of the 

component products. Empatic managed 

to achieve a synergistic effect at 

the low dose (6.1 percent vs. 5.5 percent 

for the sum of components) and 

racked up an even better effect at the 

high dose (7.5 percent vs. 7.6 percent). 

JMP Securities analyst Charles C. 

Duncan was especially sanguine in a 

research report. Weight loss with the 

Empatic combination of drugs was 

“unquestionably additive,” and 

Empatic’s efficacy and safety “more 

than meets the FDA’s recommendations 

for having benefit over the drug’s components.” 

The fact that Empatic goes 

beyond the agency’s minimum efficacy 

bar is “a much more significant factor,” 

Duncan wrote. 

In its latest 24-week, 729-patient study 

to report, Empatic gained efficacy that 

fell between Qnexa, from Mountain 

View, Calif.-based Vivus Pharmaceuticals 

Inc., and Contrave. The placebo-adjusted 

weight loss at the high and low doses 

turned up total efficacy results that did 

not level out at 24 weeks, which suggested 

the 52-week outcomes would 

show more shearing of poundage. No 

serious adverse events surfaced in the 

Empatic safety arm, nor did a signal for 

depression, cognitive function or suicidal 

thoughts emerge, and the finish 

rate hit about 60 percent, which is 

about right for trials in obesity. 

Contrave is on its way to becoming a 

first-line option for the condition, with 

Empatic as the second-line choice. 

The Phase III trials for Empatic will cost 

around $100 million, Orexigen estimates, 

and Leerink Swann analysts – 

who predict Empatic could sell more 

than $1 billion at its peak – do not 

expect the study to begin until more 

funding lands in the company’s coffers.

Wall Street is watching for news of a 

partner, and waiting to see whether 

that partner will go for a “two-for-one” 

deal. Many factors will play a role in 

how soon the Phase III trials begin, Kim 

said, including talks with the FDA and 

partners. “We are waiting to see how 

those things play out,” he said. 

Meanwhile, Leerink points out, Orexigen 

could work the obesity-specialist market 

with a focused sales push of its own, 

similar to what CV Therapeutics Inc. did 

with the chronic angina therapy Ranexa 

(ranolazine extended-release tablets), 

before CVT was taken over by Gilead 

Sciences Inc., of Foster City, Calif., in a 

$1.4 billion deal. 

Empatic Meets Endpoint in Phase IIb 

In September 2009, Orexigen 

announced that its 24-week, Phase IIb 

trial with Empatic for obesity met its primary 

efficacy endpoint by demonstrating 

statistically significantly greater 

weight loss for both Empatic doses 

compared to monotherapies and placebo. 

The company said it planned to 

meet with the FDA for an end-of-Phase- 

II meeting and to define a Phase III plan. 

NeuroSearch – tesofensine 

NeuroSearch AS, of Ballerup, Denmark, 

is advancing tesofensine, a monoamine 

reuptake inhibitor, set to start Phase III 

testing in obesity. Tesofensine is 

designed to inhibit the presynaptic 

uptake of the neurotransmitters noradrenaline, 

dopamine and serotonin in 

the brain. The company concluded an 

end-of-Phase II meeting with the FDA 

in August 2009 and expects to finalize 

a special protocol assessment, while 

continuing partnering discussions. It 

also aims to complete a licensing deal 

for the compound. “We would hope to 

do it prior to initiating a Phase III, so 

that financing would be secured,” said 

NeuroSearch spokeswoman Hanne 

Leth Hillman in early 2009. 

Tesofensine Phase II Data Are 

Released 

In October 2008, NeuroSearch said 

results of a Phase II proof-of-concept 

study showed that its obesity compound 

tesofensine produced a weight 

loss twice that of currently approved 

obesity drugs. Patients in the randomized, 

placebo-controlled Phase II study 

were prescribed a limited-energy diet 

and assigned to once-daily dosages of 

tesofensine 0.25 mg (52 patients), 0.5 

mg (50 patients), 1 mg (49 patients) or 

placebo (52 patients) for 24 weeks. The 

primary outcome was percentage 

change in body weight. A total of 161 

patients completed the study, and 

mean weight loss recorded for placebo 

and diet was 2.2 kg and for tesofensine 

0.25 mg, 0.5 mg and 1 mg was 6.7 kg, 

11.3 kg, and 12.8 kg, respectively. 

Surface Logix – SLx-4090 

SLx-4090, from Boston-based Surface 

Logix Inc., is an oral microsomal triglyceride 

transfer protein (MTP) inhibitor 

designed to act specifically in enterocytes, 

the absorptive cells in the intestine, 

where it blocks the uptake of 

triglycerides and cholesterol. Unlike 

other MTP inhibitors, its specificity 

means that it does not have systemic 

effects and related toxicities, said CEO 

Keith Dionne. The drug is in Phase IIb 

clinicals for dyslipidemia and for Type II 

diabetes and obesity. 

Arete Therapeutics – AR9281 

At the American Diabetes Association 

annual scientific session in New Orleans 

in June 2009, Arete Therapeutics Inc., 

of South San Francisco, made three 

presentations on AR9281, an orally 

administered soluble epoxide hydrolase 

(sEH) inhibitor that is in a Phase II program 

for the treatment of Type II diabetes, 

saying the data showed that 

AR9281’s safety and pharmaceutic 

properties in normal healthy volunteers, 

and evidence of its efficacy in animal 

models of Type II diabetes, supported 

further development. A Phase IIa multicenter, 

double-blind, placebo-controlled 

study in prediabetic patients 

with impaired glucose tolerance, mild 

obesity and mild to moderate hypertension 

is under way, and the company 

said those results are expected in the 

first quarter of 2010. According to the 

company’s website, the drug may have 

potential in the treatment of obesity as 

well. 

Shionogi – S-2367 

S-2367 (Velneperit) from Shionogi & 

Co. Ltd., of Osaka, Japan, is in Phase IIa 

clinicals. 

Amylin Pharmaceuticals and Takeda 

Pharmaceutical – davalintide 

Amylin Pharmaceuticals Inc.’s davalintide 

is a second generation amylin analog 

and is the company’s second lead 

clinical-stage program in the obesity 

pipeline, currently in Phase II clinicals. It 

is being studied as a stand-alone therapy 

as well as in combination with other 

hormones. 

In November 2009, Amylin signed a $1 

billion-plus deal to co-develop obesity 

compounds with Japanese partner 

Takeda Pharmaceutical Co. Ltd. The 

deal covers Phase II obesity compounds 

pramlintide/metreleptin and davalintide 

in Amylin’s pipeline and also includes 

additional compounds from both companies’ 

obesity research programs. 

Under the deal, Amylin will receive $75 

million up front and could draw more 

than $1 billion in additional payments 

for achieving milestones over the term 

of the agreement. 

TransTech Pharma – TTP435 

TTP435, from High Point, N.C.-based 

TransTech Pharma Inc., in Phase II clinicals. 

It was identified using TTP 

Translational Technology. According to 

the company’s website, TTP435 was 

assessed in a series of in vitro and in 

vivo studies as proof of concept to 

demonstrate the value of inhibiting 

AgRP as a safe and effective treatment 

for obesity. It has no effect on MC4R 

alone or in the presence of alpha-MSH. 

In animal models of obesity, “TTP435 

was shown to reduce food intake and 

body weight gain, reduce fat composition, 

and reduce insulin levels in a dose 

dependent fashion.” 


54 

7TM Pharma – TM30339 

7TM Pharma A/S, of Horsholm, 

Denmark, has TM30339 in development 

for the treatment of obesity and 

related metabolic disorders. The drug is 

designed to work via the Y4 receptor to 

mimic a natural satiety signal from the 

gastrointestinal tract involved in the regulation 

of food. 7TM Pharma initiated a 

Phase I/IIa trial with the drug candidate 

in the fall of 2008. The study is a double-blind, 

placebo-controlled 28-day 

study, which enrolled patients with a 

body mass index between 30 and 40. 

The aim is to determine the effective 

dose for inducing weight loss, for use in 

longer-term weight loss trials and also 

to assess the safety and tolerability of 

TM30339. The study is being conducted 

at multiple centers under an open investigational 

new drug application. 

In February 2008, 7TM Pharma reported 

positive results from two clinical 

studies of obesity drug TM30339. 

Results from a Phase Ia study demonstrated 

that the drug is safe and well 

tolerated when single doses are 

administered, resulting in very substantial 

and persistent plasma levels of 

the drug. A Phase Ib study in obese 

patients confirmed that safety and tolerability 

profile, including up to 14 

days of dosing. 

7TM Pharma – Obinepitide 

Horsholm, Denmark-based 7TM 

Pharma A/S is developing Obinepitide 

(TM30338), an analogue of two natural 

human hormones – PYY3-36 and 

Pancreatic Polypeptide – which are 

released in connection with food 

intake. According to the company, 

Obinepitide has a dual selectivity profile, 

and targets both the Y2 and Y4 

receptors. Preclinical studies in dietinduced 

obese animals showed that 

Obinepitide demonstrated superiority 

in the long-term reduction in body 

weight when compared to PYY3-36, a 

natural hormone that targets only the 

Y2 receptor. In a first-in-man Phase I/II 

clinical trial, the drug was safe and welltolerated. 

It is in Phase I/II clinicals. 


OSI Pharmaceuticals – PSN821 

OSI Pharmaceuticals Inc.’s PSN821, a 

novel, orally available agonist of the Gprotein 

coupled receptor GPR119, is in 

Phase I development for the treatment 

of Type II diabetes. According to the 

Melville, N.Y.-based company, PSN821 

has potential utility in obesity as well. In 

May 2009, OSI said PSN821 completed 

a single-dose Phase I trial in healthy volunteers 

and diabetes patients, where 

evidence of glucose lowering was seen 

in response to a standard nutrient challenge. 

At the American Diabetes 

Association meeting in San Francisco in 

June 2008, OSI said preclinical data 

suggested that PSN821 demonstrated 

pronounced glucose lowering in rodent 

models of Type II diabetes with no loss 

of efficacy on repeated administration, 

and substantial reductions of body 

weight in a rodent model of obesity. 

OSI Pharmaceuticals – PSN602 

OSI Pharmaceuticals Inc., of Melville, 

N.Y., is developing PSN602, an oral 

dual monoamine reuptake inhibitor 

and 5-HT1A agonist, for the treatment 

of obesity. In May 2009, OSI said that 

PSN602 completed a Phase I trial, 

where indications of activity in the 

form of significant reductions in food 

intake in standardized meal intake 

assessments were seen after 14 days 

of dosing in overweight or obese 

patients. OSI initiated the first-inhuman 

study of PSN602 in June 2008. 

The same month, at the American 

Diabetes Association meeting in San 

Francisco, OSI said PSN602 was shown 

to be as effective as a high dose of 

sibutramine, a dual serotonin (5- 

HT)/norepinephrine (NE) reuptake 

inhibitor approved for the treatment 

of obesity, at reducing body weight in 

a rodent model of obesity, but exhibited 

a more favorable cardiovascular 

profile after single doses. 

AstraZeneca – AZD4017 

AstraZeneca plc’s AZD4017 is in Phase I 

clinicals for diabetes and obesity. It is an 

11B-hydroxysteroid dehydrogenase 

(11BHSD) inhibitor. 



clinicals for diabetes and obesity. It is an 

11BHSD inhibitor. 



clinicals for diabetes and obesity. It is a 

diacylglycerol acyltransferase-1 (DGAT- 

1) inhibitor. 

Emisphere Technologies – Oral 

Peptide YY (PYY) 

Cedar Knolls, N.J.-based Emisphere 

Technologies Inc. has Oral Peptide YY 

(PYY) in Phase I clinicals. PYY is a gastrointestinal 

hormone secreted after 

meals by the endocrine cells of the distal 

gastrointestinal tract, in proportion 

to the caloric content of the meal. 

According to Emisphere, published clinical 

evidence shows that elevated PYY 

levels contribute to both decreased 

food intake and weight loss. 

TransTech Pharma – HPP404 

TransTech Pharma Inc., of Bagsvaerd, 

Denmark, has HPP404 in Phase I clinicals. 

HPP404 is a selective H3 receptor 

antagonist that is “effective in producing 

sustained reductions of food intake and 

impressive reductions of body weight in 

rodent models of obesity,” according to 

the company’s website. In animals, the 

candidate has demonstrated significant 

reduction in food intake, body weight 

gain and total body fat, as compared to 

Sanofi-Aventis Group’s Acomplia (rimonabant), 

a CB1 antagonist. 

Surface Logix – SLx-2119 

Surface Logix Inc. has SLx-2119, a Rhoassociated 

kinase 2 (ROCK2) inhibitor, 

in Phase I clinical trials for obesity. 

According to the company, ROCKs “are 

serine/threonine protein kinases that 

serve as key downstream effectors of 

the Rho GTPase, RhoA, and play an 

important role in cytoskeletal function.” 

ROCK enzymes exist as two isoforms, 

ROCK1 and ROCK2, and studies 

indicate that each one has a distinct 

role. Surface Logix’s program has produced 

the only known inhibitors for

ROCK2 and “has demonstrated significant, 

non-CNS mediated weight loss 

with improved lipid and glucose metabolic 

profiles through the selective inhibition 

of ROCK2.” 

Zafgen – ZGN-433 

Zafgen Inc., of Cambridge, Mass., is 

developing therapeutics to treat obesity 

based on vascular targeting in adipose 

tissue (fat). ZGN-433 (administered 

intravenously) is in a Phase Ib proof-ofconcept 

clinical in Melbourne, 

Australia. 

In January 2009, Argenta Discovery 

Ltd., of Harlow, UK, and Zafgen 

entered a collaboration to use 

Argenta’s computer-aided drug design, 

medicinal chemistry, assay development, 

in vitro screening, drug metabolism 

and pharmacokinetics to accelerate 

development candidate for one of 

Zafgen’s therapeutics programs for 

obesity. Financial terms were not disclosed. 

Early Stage Development Efforts in 

Obesity 

A number of other companies are 

active in obesity research. The following 

section highlights the R&D efforts, and 

business development and financing 

initiatives, of biopharma companies in 

the preclinical and research stages in 

the field of weight loss. For more products 

in early stage development, see the 

table “Obesity Drugs in Development.” 

7TM Pharma – TM38837 

7TM Pharma A/S, of Horsholm, 

Denmark, is in preclinicals with the 

Cannabinoid type 1 (CB1) antagonist 

TM38837 for obesity and metabolic 

diseases. It has shown weight reduction 

in various chronic animal models of 

obesity. In clinical trials, CB1 antagonists 

have demonstrated the ability to 

reduce body weight and improve the 

risks associated with obesity, such as 

Type II diabetes. Drugs that exert their 

effects through CB1 receptors in the 

brain come with a number of side 

effects. According to 7TM Pharma, 

TM38837 was designed to exert its 

therapeutic effect through CB1 receptors 

in the peripheral tissue in order to 

avoid such side effects. 

Aegis Therapeutics 

In August 2009, Aegis Therapeutics 

LLC, of San Diego, and Albany Medical 

College in Albany, N.Y., expanded their 

existing research relationship to include 

a joint commercialization deal for promoting 

clinical development of the college’s 

obesity peptide drug. Under the 

terms, Aegis will be responsible for 

developing an appropriate pharma 

partnership to commercialize the drug 

in obesity and diabetes indications. 

Agios Pharmaceuticals 

The same set of molecules that 

Cambridge, Mass-based biotech startup 

Agios Pharmaceuticals Inc. plans to 

develop for cancer also will be studied 

for use in other therapeutic areas such 

obesity/diabetes, autoimmune, inflammatory 

and neurological diseases. 

AstraZeneca 

AstraZeneca Gains Obesity Program 

from Biovitrum 

In late 2009, Biovitrum AB announced 

that it was divesting its obesity program 

to AstraZeneca plc in a potential £186 

million (US$265.6 million) deal. The 

London-based pharma firm will gain 

rights to all of Biovitrum’s assets relating 

to the leptin modulator program in 

obesity. In exchange, Stockholm, 

Sweden-based Biovitrum will get an 

up-front payment of £6 million. If a 

product is approved, the deal allows for 

up to £186 million in up-front and milestone 

payments. Biovitrum also would 

be entitled to single-digit royalties. 

BioVista 

BioVista Inc. has drugs in various stages 

of research and preclinical development 

for eye disorders, diabetes and obesity. 

According to its website, the 

Charlottesville, Va.-based company has 

identified four novel targets involved in 

diabetes and obesity that lend themselves 

to the development of RNAi drugs. 

Using artificial intelligence (AI), 

BioVista created a drug profiling platform 

that can identify new uses for 

existing compounds, providing the 

start-up with dozens of options for 

internal development as well as partnerships 

and financing. The company 

began as a research project run by 

brothers Aris and Andreas Persidis. 

About 15 years ago, the brothers set 

out to apply AI and engineering concepts 

to the life sciences. Andreas 

Persidis explained that merging ideas 

from two disparate fields often provides 

out-of-the-box solutions. But it 

wasn’t until early 2008 that BioVista 

vaulted from research project into 

corporate mode. That’s when the 

brothers and their team discovered 

how to endow their data management 

platform with an awareness of 

concepts like drugs, diseases, side 

effects, organs, genes, biological 

pathways and more. They then 

applied the technology to 8,000 diseases, 

12,000 adverse events and 

15,000 drugs from the world’s formularies, 

using every scientific publication, 

conference presentation, FDA 

report and patent filing available. 

It would be easy to dismiss BioVista’s 

technology as data mining, but 

Andreas Persidis explained that it is 

“not a case of reshuffling existing information, 

but creating new things.” 

Biotech and pharma companies apparently 

understand the distinction. 

BioVista has eight ongoing projects that 

involve using its technology to provide 

discovery, repositioning, adverse event 

profiling, patient stratification and 

other services for partners. All of the 

company’s deals involve not just fees 

but milestone payments and future royalties, 

Aris Persidis said. 

Yet BioVista is more than just a service 

provider. The company wanted to 

“practice what we preached” and 

develop an internal pipeline, Andreas 

Persidis said. So the BioVista team selected 

unmet medical needs and applied its 

platform to identify generic drugs that 


56 

might find a new use meeting those 

needs. The strategy resulted in an internal 

pipeline comprising more than 30 

repurposed generic compounds. 

Braasch Biotech 

Braasch Biotech LLC, of Chicago, has a 

lead vaccine for obesity and growth 

hormone deficiencies. In September 

2009, the company said the vaccine 

may have beneficial use for numerous 

IGF-1 responsive disorders such as diabetes, 

heart disease and Rett syndrome 

based on initial preclinical testing in a 

mouse model. The vaccine’s mode of 

action is to generate highly specific 

antibodies, which attenuate but do not 

entirely eliminate the mostly inhibitory 

actions of somatostatin. Braasch’s 

approach allows the body to do that on 

its own without using drugs. 

Cambridge Biotechnology / 

Proximagen Neuroscience 

Proximagen Adds Pain, Obesity 

Drugs in Cambridge Biotech Buy 

London-based Proximagen Neuroscience 

plc acquired Cambridge Biotech 

Ltd. from Biovitrum AB in November 

2009, and it now operates as a wholly 

owned subsidiary of Proximagen. 

Cambridge’s projects focus on obesity, 

diabetes, glaucoma and pain, primary 

care areas that involve heavy competition 

from major players, Erik Kinnman, 

executive vice president of Biovitrum, 

told BioWorld. Cambridge’s compounds, 

Kinnman said, would expand 

the Proximagen pipeline, which previously 

was focused on central nervous 

system disorders such as Parkinson’s 

disease. Cambridge’s portfolio includes 

a small-molecule mimetic of the metabolic 

hormone leptin in obesity, which 

the firm said has demonstrated compelling 

weight-reducing effects in wellestablished 

animal models. 

Cambridge was acquired for a percentage 

of any future revenues generated 

from the Cambridge pipeline. Under 

the deal, announced in the fall of 2009, 

Proximagen gains Cambridge’s pipeline 

of small molecules focused on pain and 


obesity. Financial terms were not disclosed. 

By dropping Cambridge Biotech, 

Kinnman said, Biovitrum could stay 

focused on specialty niche indications 

such as hematology, rheumatology, 

oncology and endocrinology. 

CeNeRx BioPharma 

CeNeRx BioPharma Inc. has a preclinical 

portfolio of cannabinoid compounds, 

which it licensed from PharmaNess 

Neurosciences Scarl of Pula, Italy. 

Preclinical proof-of-concept studies 

have been completed in pain, obesity, 

glaucoma and spasticity. In October 

2009, Research Triangle Park, N.C.based 

CeNeRx said it was looking to 

partner its preclinical portfolio, which 

contains 18 compounds and is more 

than it can develop internally. 

Colby Pharmaceutical – CPC-410 

CPC-410, which Menlo Park, Calif.based 

Colby Pharmaceutical Co. discovered 

internally, is a mitochondria-targeted 

small molecule designed to 

reverse hypoxia and hit cancer stem 

cells within metastatic tumors, including 

glioblastoma. The compound also 

may have applicability in neurodegenerative 

diseases and obesity. 

Compellis Pharmaceuticals – CP404 

Compellis Pharmaceuticals Inc. is a 

Boston-based firm that hopes to tackle 

obesity by inhibiting olfactory neurosensory 

function. According to 

President and CEO Chris Adams, it has 

been well documented that “people 

with smell and taste disorders stay the 

same weight or often lose weight.” 

Founded in 2004 to focus on repurposing 

drugs to treat central nervous system 

disorders, Compellis tagged the 

obesity market as its first project. It was 

a market “we decided, that wasn’t very 

well served,” Adams told BioWorld. 

“We saw very few compounds and 

drugs out there.” 

Compellis’ lead program is CP404, with 

the active ingredient diltiazem, which 

has been on the market for about 20 

years in the hypertensive space. CP404 is 

designed to be administered intranasally, 

which means it should avoid systemic 

symptoms. In preclinical studies, the product 

“blocked the smell in rats with no side 

effects,” Adams said. And rats receiving 

diltiazem gained “30 percent less weight 

than rats not on the drug.” CP404, a calcium 

channel blocker, is designed to 

specifically target calcium channels in the 

olfactory epithelial layer, which contains 

olfactory receptors, he said. “The odor in 

the atmosphere binds to the receptors” 

and the “calcium channel is active in 

sending signals to the brain. “So if you 

can block that channel, then you won’t 

get the [olfactory] cues and won’t be 

stimulated,” he added. And, since “taste 

is 80 percent smell, food won’t taste as 

appetizing.” Compellis is designing 

CP404 to be taken twice-daily for 12 

weeks to 15 weeks. 

As of November 2008, the company 

had filed an investigational new drug 

application and was set to begin Phase 

I testing, which Adams expected to finish 

up in about six months. Compellis is 

collaborating on Phase I testing with 

the Pennington Biomedical Research 

Institute at Louisiana State University. 

Assuming success, the plan is to take 

CP404 through Phase II development 

and then look to partner, Adams said. 

“We may even look at an OTC strategy 

as well.” 

Corcept Therapeutics – CORT 108297 

Corcept Therapeutics Inc., of Menlo 

Park, Calif., is developing preclinical 

candidate CORT 108297 for the prevention 

of antipsychotic-induced weight 

gain. CORT 108297 is a nonsteroidal 

cortisol receptor (GR-II) antagonist that 

produced promising results in a human 

microdosing study. The study involved 

the administration of subpharmacological 

doses of CORT 108297 to human 

subjects without extensive animal testing. 

The results showed that the compound 

has good bioavailability with a 

half-life that may be compatible with 

once-a-day oral dosing. Corcept is 

studying disease states associated with 

excess production of cortisol, the

“stress” hormone, which, in excess, 

might play a role in the pathogenesis 

of several important metabolic diseases 

including diabetes, obesity and 

hypertension. 

DeveloGen 

DeveloGen AG, founded in 1997 by scientists 

at the Max Planck Institute and 

the University of Freiburg, specializes in 

discovering and developing therapies 

for the treatment of metabolic and 

endocrine diseases. Its preclinical pipeline 

targets the key drivers of diabetes and 

obesity such as insulin resistance and 

loss of insulin-producing beta cells. The 

pipeline includes two lead programs, a 

small-molecule inhibitor based on a 

novel target to address insulin resistance 

in Type II diabetes and a growth factor 

targeting beta-cell regeneration for Type 

I and Type II diabetes. 

A key to Goettingen, Germany-based 

DeveloGen’s discovery efforts is first-inclass 

insulin sensitizers that block signals, 

which negatively interfere with 

the transduction of the insulin signal, 

thus increasing the ability of the body’s 

cells to respond to insulin. Its beta cell 

regeneration factor is a secreted molecule 

that stimulates beta cell proliferation 

and neogenesis, promoting the 

regeneration of the beta cell mass and 

ensuring that the body provides 

enough endogenous insulin to maintain 

glycemic control. 

DeveloGen’s Preclinical Diabetes 

Package Draws $330M from BI 

DeveloGen picked up $9.5 million up 

front with hope for $321 million long 

term in a preclinical diabetes deal with 

Boehringer Ingelheim GmbH signed in 

May 2009. While no specific compounds 

were named, the asset sale and 

collaboration agreement targets the field 

of diabetes, obesity, metabolic syndrome 

and other insulin resistance-associated 

disorders. Under the agreement, 

DeveloGen will receive an up-front payment 

of €7 million (US$9.5 million) and 

can earn additional deferred payments 

such as potential milestones of up to 

€237 million, plus tiered sales performance 

payments. The milestone payments 

are tied to preclinical, clinical, regulatory 

and commercial events. Even more milestone 

payments are possible with additional 

compounds or additional 

approved indications, the companies 

said. DeveloGen also will receive research 

payments to support further discovery 

and development efforts. DeveloGen 

CEO Cord Dohrmann praised the partnership 

with BI in a statement, saying it 

“has built an impressive late-stage 

pipeline of innovative metabolic disease 

programs. We are convinced that the 

leadership by Boehringer Ingelheim will 

provide optimal support for further development 

of this program.” 

Elixir Pharmaceuticals 

Elixir Pharmaceuticals Inc., of Cambridge, 

Mass., has three candidates in development 

with potential obesity applications. 

It has a ghrelin antagonist for 

Type II diabetes and obesity in preclinicals; 

a SIRT1 activator for Type II diabetes 

and obesity in preclinicals; and a 

SIRT2 inhibitor for Type II diabetes and 

obesity in research. 

Fasgen 

Fasgen Inc., of Baltimore, says that its 

“proprietary compounds provide a 

totally new approach to the treatment 

of obesity because they selectively 

modify food ingestion and reduce body 

fat while sparing lean tissues.” It has 

evaluated more than 100 new chemical 

entities, and its selection criteria 

include: “critria reversible inhibition of 

fatty acid synthase (FAS), stimulation of 

carnitine palmitoyl transferase 1 (CPT-1) 

activity, inhibition of mitochondrial glycerol-3aclytransferase 

(GPAT), increased 

rate of fatty oxidation, lack of cytotoxicity 

to hypothalamic neurons and other 

normal cells, lack of mutagenicity, and 

favorable pharmacologic characteristics 

such as oral bio-availability.” Initial studies 

revealed that FAS 267 inhibits FAS 

located in the specialized nuclei in the 

brain stem, which control feeding 

behavior. Weight loss is caused when 

levels of AMPK fall, the expression of 

neuropeptide Y (NPY) is reduced and 

then food intake is restricted. FAS 89B 

stimulates the activity of CPT-1 in 

peripheral tissues. This causes an 

increased rate of fatty acid oxidation 

and a selective reduction in body fat. 

FAS 115 primarily inhibits GPAT. 

In October 2009, Fasgen was awarded 

a $1.4 million Phase II Small Business 

Innovation and Research Grant from 

the National Institutes of Health for 

continued research into obesity. The 

current research effort will optimize the 

company’s compounds for use in future 

clinical trials. The research is in part conducted 

in cooperation with labs at 

Johns Hopkins University. 

Genfit – TGFTX2 

Genfit SA’s pipeline includes TGFTX2, 

in discovery for obesity and Type II 

diabetes. 

Genfit, Pierre Fabre Renew 

Metabolic Disorders Pact 

In January 2008, Genfit, of Lille, France, 

and Pierre Fabre, of Castres, France, 

renewed a strategic research collaboration 

that was first signed in 2001. The 

two companies have been undertaking 

several joint research programs since 

then, and have been concentrating 

more specifically on two drug discovery 

programs targeting metabolic disorders 

since 2005. The companies said they 

identified a first-in-class group of molecules 

that could have a simultaneous 

therapeutic effect on Type II diabetes 

and dyslipidemia, as well as a potential 

effect on obesity, specifically through a 

phenotypic approach. The two parties 

planned to embark on the first regulatory 

studies for one of those compounds 

within 18 months. The terms of their 

alliance give Pierre Fabre Laboratories 

exclusive rights to the commercialization 

of products emerging from the collaboration, 

while Genfit will continue to 

receive research funding, milestone payments 

and royalties. 

Genfit’s activities are focused on the 

deregulation of genes involved in com- 


58 

mon diseases. It is developing proprietary 

drugs to treat global cardiovascular 

and metabolic risk and is engaged in collaborations 

with leading pharmaceutical 

companies that are developing therapies 

for the most prevalent metabolic and 

inflammatory diseases. Describing its collaboration 

with Pierre Fabre as exceptional, 

Genfit CEO Jean-François 

Mouney pointed out that the two companies 

had “profiled a large number of 

compounds in order to identify the best 

candidates for an innovating therapeutic 

solution in the area of Type II diabetes 

and specific risk factors associated with 

cardiometabolic disease.” And he added 

that other large pharmaceutical companies 

were interested in “the promising 

targets that are the focus of our collaboration 

with Pierre Fabre.” 

Halsa Pharmaceuticals – ZAG 

Halsa Pharmaceuticals Inc., of Houston, 

is developing ZAG (Zinc-Alpha-2- 

Glycoprotein) for the treatment of diabetes 

and obesity. ZAG, a natural regulator 

of fat in humans and other animals, 

is a recombinant protein that will 

increase ZAG levels in obese patients to 

normal levels, as well as reduce body 

fat to normal levels. Halsa holds exclusive 

patent rights to the natural material, 

which is believed to cause immediate 

and substantial depletion of body 

fat when injected into an obese patient. 

In March 2008, Halsa was awarded 

$250,000 from the Texas Emerging 

Technology Fund to continue development 

and pilot manufacturing of a 

therapeutic treatment for obesity. The 

TETF may provide up to $1 million total 

investment if the company meets certain 

performance benchmarks. 

Intercept Pharmaceuticals – INT-777 

Intercept Pharmaceuticals Inc., of New 

York, is developing INT-777, a selective 

TGR5 agonist. The company said that a 

paper published in the Sept. 2, 2009, 

issue of Cell Metabolism reported on 

the mechanism of action of INT-777, 

providing a clear rationale for its potential 

as a novel treatment in diabetes, 


obesity and associated metabolic disorders. 

INT-777 is a patent-pending modified 

human bile acid that was discovered 

by Intercept. INT-777 induces the 

release of GLP-1 in the gut and normalizes 

glucose tolerance, making it applicable 

for both diabetes and obesity. The 

candidate is in preclinicals. 

Isis Pharmaceuticals 

Isis Pharmaceuticals Inc., of Carlsbad, 

Calif., is pursuing the discovery and 

development of antisense drugs for diabetes 

and obesity. It has four drugs in 

its pipeline for the treatment of Type II 

diabetes, and it is evaluating obesity 

targets. For example, ISIS 113715, an 

antisense inhibitor of protein tyrosine 

phosphatase 1B (PTP-1B), may have 

potential in obesity. 


scientific session in New Orleans in June 

2009, data were presented from Isis’ 

anti-obesity drug discovery program 

showing antisense drugs reduced fat 

mass and body weight in animals by 

reducing levels of targets in peripheral 

tissues such as liver and fat without 

affecting the central nervous system. 


meeting in San Francisco in June 2008, 

Isis said results from some of its 

research programs showed that antisense 

technology reduced mRNA target 

levels in specific tissues and provided 

early signs of therapeutic benefit in various 

models of disease, offering robust 

and sustained effects for the treatment 

of obesity, Type II diabetes and lipid 

metabolism disorders. 

Marcadia Biotech 

Marcadia Biotech Inc., of Carmel, Ind., 

is developing biopharmaceutical therapies 

for diabetes and obesity. Marcadia 

said results of a novel pharmacological 

treatment that demonstrated significant 

weight loss in animal models of 

obesity was published in the October 

2009 issue of Nature Chemical Biology. 

Researchers describe a new approach 

combining the mechanisms of two nat- 

ural hormones to accentuate weight 

loss within one drug candidate. 

Glucagon and GLP-1 are two peptide 

hormones that are known predominantly 

for their regulation of glucose 

metabolism. The publication describes 

the chemical and biological integration 

of their pharmacology to deliver 

enhanced weight loss and glucose control 

without any apparent side-effects. 

In March 2008, Marcadia entered a collaboration 

with Whitehouse Station, 

N.J.-based Merck & Co. Inc. to jointly 

discover, develop and commercialize 

therapies targeting the glucagon and 

related receptors to treat diabetes and 

obesity. Under the terms, Merck will 

gain a worldwide license to certain 

Marcadia development candidates and 

intellectual property, in exchange for an 

initial up-front fee, as well as payments 

for exclusivity and ongoing collaborative 

research. Marcadia also will be eligible 

to receive future milestone and 

royalty payments, and will have the 

right to exercise options for profit-sharing, 

cost-sharing and co-promotion in 

the U.S. Specific financial terms were 

not disclosed. 

Merck 

New York-based Merck & Co. Inc. has a 

diabetes and obesity franchise. 

Merck Signs Discovery Collaboration 

with Envoy 

In January 2010, Envoy Therapeutics 

Inc., of Jupiter, Fla., signed a diabetes 

and obesity drug discovery collaboration 

with Merck. Envoy will use its bacTRAP 

platform to identify proteins expressed 

in certain cell types, and Merck will 

develop compounds to modulate the 

protein targets. Specific financial terms 

were not disclosed, but Envoy gets an 

up-front fee, research funding, milestone 

payments and royalties. 

Galapagos, Merck in Potential 

€170M Obesity, Diabetes Deal 

In January 2009, Mechelen, Belgiumbased 

Galapagos NV signed its fifth 

major pharmaceutical alliance, inking a

potential €171.5 million (US$230.4 

million)-plus deal with Merck to 

develop drugs aimed at the obesity 

and diabetes markets. Galapagos’ 

role is to discover small-molecule candidate 

drugs for preclinical development, 

with payment in terms of an 

up-front fee of €1.5 million, and on 

meeting agreed goals in preclinical 

and clinical development of candidates, 

plus royalties on worldwide 

sales. Merck will have the exclusive 

option to license each candidate for 

clinical development and commercialization 

on a worldwide basis. 

The alliance will make use of 

Galapagos’ SilenceSelect discovery platform, 

and after validation, targets will 

be chosen by a joint steering committee 

and entered into screening and 

chemistry by Galapagos. Merck has the 

option of acquiring an exclusive license 

to each candidate drug and to become 

responsible for its development and 

commercialization. Galapagos may execute 

Phase I studies and will have the 

right to further develop and commercialize 

certain compounds for which 

Merck does not exercise its exclusive 

option. Galapagos is eligible for discovery, 

development and regulatory milestones 

that could exceed €170 million 

total for multiple products, as well as 

specific sales milestones and royalties 

on any product sales. 

Myriad Pharmaceuticals – 

MPI-0485520 

Myriad Pharmaceuticals Inc., of Salt Lake 

City, has identified an investigational new 

drug candidate, MPI-0485520, targeting 

the protein kinase IKK epsilon. The target 

was identified as a central regulator of 

chronic inflammation, obesity and diabetes 

in the September 2009 issue of 

Cell. Myriad expects to seek to partner 

for MPI-0485520 in obesity and diabetes 

but intends to develop it by itself. 

Obecure – OBE102 

Ramat Gan, Israel-based Obecure 

Ltd.’s OBE102 for weight loss is in preclinicals. 

Palatin Technologies 

Palatin Technologies Inc., of Cranbury, 

N.J., has a melanocortin receptor program 

for the treatment of obesity, 

which consists of five G protein-coupled 

receptors: MC1-R, MC2-R, MC3- 

R, MC4-R and MC5-R. According to 

Palatin, MC4-R seems to be the key 

melanocortin receptor involved in food 

intake regulation. For example, in 

humans, the most common form of 

monogenic obesity is caused by mutations 

in MC4-R. Signaling systems 

involved in food intake regulation and 

energy expenditure also mediate their 

effects through MC4-R. 

Palatin Partners with AstraZeneca 

for Obesity 

Palatin announced in September 2009 

that it will receive $5 million from 

London-based AstraZeneca plc relating 

to an amendment of its ongoing, exclusive 

research collaboration and license 

agreement to discover, develop and 

commercialize compounds targeting 

melanocortin receptors to treat obesity 

and related indications. Under the 

terms, AstraZeneca agreed to make a 

$2.5 million payment upon signing 

and, subject to completion of certain 

tasks, another $2.5 million payment 

will be made in the first quarter of 

2010. Terms of the original 2007 deal 

relating to milestones and royalties 

were restructured. 

A previous extension took place in 

December 2008, when Palatin 

Technologies said it had extended its 

January 2007 research collaboration 

and license agreement with 

AstraZeneca to discover, develop and 

commercialize compounds that target 

melanocortin receptors for obesity and 

other metabolic disorders. Under the 

extended terms, Palatin will receive an 

up-front payment of $1.6 million in 

exchange for additional licenses for 

compounds and patents. Palatin will be 

eligible in the near future for milestone 

payments totaling $5 million in connection 

with the collaboration and 

license agreement. Under the terms of 

the original deal, Palatin received an 

up-front payment of $10 million from 

AstraZeneca and is eligible for milestone 

payments of $300 million, with 

up to $180 million contingent upon 

development and regulatory milestones 

and the balance on achievement 

of sales targets, together with 

the payment of stepped royalties on 

product sales to double digit rates, 

dependent on sales achieved. 

AstraZeneca is responsible for product 

commercialization, product discovery 

and development costs. 

RXi Pharmaceuticals 

RXi Pharmaceuticals Corp.’s pipeline of 

RNAi compounds currently includes 

preclinical programs for familial amyotrophic 

lateral sclerosis, obesity, diabetes, 

oncology and cytomegalovirusrelated 

disorders. The company spun 

out of CytRx Corp. as an RNAi-focused 

subsidiary and gained its independence 

through a Nasdaq listing. 

In June 2008, RXi announced that it 

was raising $8.7 million through the 

private placement of 1.1 million shares 

of common stock priced at $8.12 per 

share. Proceeds from the financing will 

be used for working capital and other 

general corporate purposes, such as 

building the company’s pipeline for 

potential alliances, internal development 

and collaborations. 

Sirona Biochem 

Sirona Biochem Corp., of Vancouver, 

British Columbia, is focused on the 

development and commercialization 

of a new class of sodium glucose 

transporter (SGLT) inhibitors for the 

treatment of Type II diabetes and obesity. 

In July 2009, Sirona Biochem 

received its first batch of SGLT 

inhibitors from partner TFChem Sarl, 

of Rouen, France. Sirona plans to 

screen the SGLT library for potential 

diabetes and obesity drugs. 

In September 2009, Sirona Biochem 

announced that it received a contribution 

of up to $70,000 from the 


60 

National Research Council of Canada 

Industrial Research Assistance Program 

to support its drug development work in 

obesity and diabetes. In addition, the 

company also will receive both technical 

and business-oriented advisory services 

provided by NRC-IRAP. In other news, the 

company said it has validated the concept 

that its GlycoMim technology can 

inhibit the glucose transporter SGLT2. 

Transition Therapeutics 

With big pharma deals in place for its 

two lead compounds, Transition 

Therapeutics Inc., of Toronto, replenished 

its pipeline in August 2008 by 

acquiring three early stage programs 

from Forbes Medi-Tech Inc. Transition 

acquired programs evaluating smallmolecule 

acetyl-CoA carboxylase 2 

(ACC2) inhibitors for diabetes and obesity 

and serine palmitoyltransferase 

(SPT) inhibitors for inflammation. 

Unigene Laboratories – UGP281 

In December 2009, Unigene Laboratories 

Inc., of Boonton, N.J., selected UGP281 

as the lead peptide from its obesity program. 

In preclinical studies, UGP281 was 

at least three times more effective in 

reducing food consumption than other 

peptides in clinical development, 

Unigene said. 

In January 2009, Unigene reported preclinical 

data demonstrating that its peptide 

hormone UGL269 significantly 

reduced food intake and body weight in 

dogs, outperforming an analogue of 

peptide PYY. The data were presented 

at the Keystone Symposium Conference 

on Obesity in Banff, Alberta. 

Ventana Biotech 

Ventana Biotech Inc.’s main focus is a 

chewing gum that acts as an appetite 

suppressant. If higher doses are needed, 

the drug may be administered by 

injection. According to the company’s 

website, the idea behind the product is 

“trying to emulate the body’s natural 

signals for feeling full using a drug 

based on a natural gut hormone produced 

after every meal.” 


Ventana, of New York, signed a letter 

of intent in August 2009 for a collaboration 

with PE Consortium Ltd., a 

company that specializes in R&D and 

outsourcing work for obesity drug targets. 

A deal would enhance Ventana’s 

existing sourcing efforts for obesity 

treatments. 

Xenon Pharmaceuticals 

Xenon Pharmaceuticals Inc., of Burnaby, 

Canada, is developing small molecule 

inhibitors of Stearoyl-CoA Desaturase-1 

(SCD1) for the treatment of obesity. 

SCD1 is the target for the treatment of 

obesity and its resulting consequences, 

including metabolic syndrome. 

Xenon entered an agreement with 

Basel, Switzerland-based Novartis AG in 

2004 to research, develop and commercialize 

compounds from Xenon’s 

SCD1 drug development program. 

Precommercial payments to Xenon 

under the Novartis deal total up to 

$157 million. Xenon also will receive 

royalties on products developed from 

that collaboration. 

XOMA – XOMA 052 

XOMA Ltd., of Berkeley, Calif., is in 

Phase II clinicals with XOMA 052 for 

Type II diabetes, and it is preclinical 

studies for other indications. Although 

it was engineered as a broad antiinflammatory 

agent, the company said 

XOMA 052 has potential as a treatment 

for diabetes, cardiovascular disease, 

rheumatoid arthritis, gout, systemic 

juvenile idiopathic arthritis and 

obesity. 


scientific session in New Orleans in June 

2009, XOMA said new preclinical 

results with XOMA 052 in the dietinduced 

obesity mouse model showed 

it addressed the inflammatory cause of 

Type II diabetes by targeting interleukin 

1 beta (IL-1 beta). Mice model studies 

showed reduction in glycosylated 

hemoglobin levels, fasting blood glucose 

without causing hypoglycemia, 

improvement in glucose control, 

improvement in insulin secretion and 

beta cell function, protection from dietinduced 

beta cell apoptosis, increase in 

beta cell proliferation, reduction in total 

cholesterol without reduction in high 

density lipoprotein and reduction in 

triglycerides and free fatty acids. 


meeting in June 2008, XOMA said an 

animal study showed that XOMA 052 

preserved insulin production, reduced 

fasting glucose and cholesterol levels 

and preserved beta-cell function in mice 

with a diet-induced obesity model of 

Type II diabetes. In the 14-week study, 

mice were fed either a normal diet or a 

high-fat, high-sucrose diet. Subsets 

were then treated with either twice 

weekly injections of 1 mg/kg Xoma 052 

or a negative control antibody. 

Zealand Pharma – ZP2929 

ZP2929, from Glostrup, Denmarkbased 

Zealand Pharma AS, is in preclinicals 

for Type II diabetes and obesity. It is 

a long-acting dual Glucagon-GLP-1 

agonist that has been shown to 

improve glycaemic control and to 

induce significant and sustained body 

weight loss in rodent models. 

ZenBio 

ZenBio Inc., of Research Triangle Park, 

N.C., said in January 2009 that it was 

awarded a Phase II Small Business 

Innovation Research grant to commercialize 

primary human peritoneal 

mesothelial cells. The $1.88 million 

award from the National Institutes of 

Health will fund continued optimization 

and commercial development of this 

unique tool for cancer, obesity and Type 

II diabetes research. 

In October 2008, ZenBio said it was 

awarded a Phase II Small Business 

Innovation Research grant to commercialize 

its primary human skeletal 

myocyte and adipocyte co-culture system. 

The $1.38 million award is expected 

to fund continued optimization and 

commercial development of that tool 

for Type II diabetes and obesity research.

Znomics 

In April 2008, Znomics Inc., announced 

the launch of a program to find lead drug 

compounds for the treatment of obesity. 

The Portland, Ore.-based company 

obtained from Oregon Health & Science 

University an exclusive biological license 

to a genetic model of obesity using the 

zebrafish. The company intends to refine 

that obesity model for use in the screening 

of small-molecule compounds. The 

company also aims to identify preclinical 

drug candidates for obesity and to partner 

with a company to advance such 

candidates into human clinical studies. 

Discontinued Products and Programs 

Are Prevalent in Obesity Space 

Now that both Pfizer Inc. and Merck & 

Co. Inc. have folded their Phase III obesity 

programs, perhaps it will open doors for 

biotech companies looking to compete in 

the obesity area. On the other hand, it 

could be a cautionary tale for biotechs 

with late-stage obesity programs, such as 

such as Arena Pharmaceuticals Inc., 

Orexigen Therapeutics Inc., Vivus Inc. or 

Alizyme Therapeutics Ltd. Jason Napodano, 

a senior drug analyst with Zacks 

Investment Research who tracks Arena, 

said he sees the bad news for Pfizer, 

Merck and Sanofi as “a positive for 

Arena.” Arena’s lorcaserin has a completely 

different mechanism of action 

than the CB1 drug class and has not 

shown any safety issues thus far, he said. 

Ken Trbovich, an analyst at RBC Capital 

Markets who tracks Vivus, said he sees 

good and bad news for biotech companies. 

The good news, he said, is that the 

large obesity market has the interest of 

major pharmaceutical companies, and 

there are fewer late-stage compounds to 

license or acquire. 

Along with a meager market performance 

of its approved anti-obesity drugs, 

pharma's internal R&D failures, product 

market withdrawals and corporate closings 

in the obesity sector have, no 

doubt, influenced its hesitance to invest 

and partner in the leading biotech clinical 

candidates thus far. 

The unfavorable news coming out of 

the $200 million obesity drug market is 

responsible for more than $4 billion in 

corporate losses related to failed trials, 

recalled products and insolvent companies. 

Until someone solves the R&D 

drought and produces a blockbuster 

breakthrough therapeutic, pharma’s 

cold feet market posture may force 

biotech to find late-stage facilitation, 

which is traditionally big pharma's reliable 

strong point, elsewhere. A prolonged 

extension of this uncharacteristic 

trend could have a detrimental 

effect on the progress of not only latestage 

biotech projects, but could cause 

enough anxiety and funding woes for 

early stage developers to abandon or 

fold promising obesity research. 

But the bad news is the seeming low 

tolerance of FDA for safety concerns, 

Trbovich said. In addition, he said the 

setbacks suffered by the major drugmakers 

may be a sign of risk in the 

minds of investors. 

Athersys – ATHX-105 

Athersys Inc., of Cleveland, said in 

September 2009 that the FDA 

requested additional information 

relating to the investigational new 

drug application for a 12-week Phase 

II trial of ATHX-105, the company’s 

lead product, an orally administered 

candidate for obesity, and that the 

company placed the study on partial 

hold. Athersys said the FDA’s comments 

can be addressed with data 

from ongoing or recently conducted 

studies that provided safety and tolerability 

data and also indicated that 

the drug is well absorbed throughout 

the gastrointestinal tract, thus 

demonstrating the potential for 

development of a once-per-day controlled 

release formulation. Athersys 

said because of those data, it will prioritize 

development of a modifiedrelease 

product, and adjust its clinical 

development plan to enable a meaningful 

assessment of ATHX-105 in 

both immediate-release and modified-release 

versions. 

Genaera – MSI-1436 

Despite two financial restructurings in 

the past year and a promising compound 

in the clinic, Genaera Corp. simply 

ran out of money, and its board of 

directors decided to liquidate in April 

2009. The dissolution of the company 

means that the company will be seeking 

buyers for its clinic products, all in 

diabetes and obesity. In June 2009, 

Genaera said stockholders voted in 

favor of liquidating the company. 

Genaera’s lead compound was Phase II 

candidate MSI-1436, its first-in-class, 

highly selective inhibitor of PTP1B for 

the treatment of Type II diabetes and 

obesity. In February 2009, the Plymouth 

Meeting, Pa.-based company reported 

that data from a Phase Ib trial in overweight 

and obese Type II diabetic subjects 

showed meaningful improvement 

in four primary outcomes used to evaluate 

Type II diabetes, including a 9.5 

percent decrease in fasting blood glucose 

with a resulting 17 percent differential 

compared to placebo subjects. 

The company’s first restructuring came 

in May 2008 when it reduced executive 

pay by 10 percent, cut out bonuses and 

reduced headcount by 34 percent to 

help conserve cash. The company 

ended 2007 with about $21 million in 

cash, and that shrunk to about $8 million 

as of Dec. 31, 2008. Then in March 

2009, Genaera announced an 80 percent 

staff reduction. 

MDRNA – PPY(3-36) 

While looking to shed its nasal business 

and transition to gene-silencing agents, 

MDRNA Inc. in August 2008 reported 

disappointing results from a Phase II 

trial of its nasal spray treatment for 

obesity and positive preclinical data for 

its gene-silencing agent showing 

reduced weight and cholesterol levels 

in a mouse model. The unfavorable 

Phase II study showed that the company’s 

peptide, PYY(3-36), was not effective 

as a single agent for weight loss. 

Nor did the peptide provide greater 

weight loss than obesity drug Merida 


62 

(sibutramine). However, the company 

noted that the peptide was shown to 

be delivered effectively to the body via 

nasal administration. In addition, there 

were no occurrences of depression or 

suicidal thoughts in the patients receiving 

PYY at any time during the sixmonth 

study. 

The Bothell, Wash.-based company, 

formerly Nastech Pharmaceutical Co., 

had planned to out-license the product, 

no matter what the study’s outcome. 

As the company transitions to a focus 

on RNAi, it is looking to either outlicense 

individual nasal products or put 

the entire nasal business up for sale. 

“We do not plan to do further development 

on any of the nasal programs,” 

confirmed Matthew D. Haines, senior 

director of investor relations and corporate 

communications, when the study 

results were announced. 

MDRNA had three Phase II nasal programs, 

including the obesity program. 

The other two programs were a nasal 

insulin (non-pulmonary) for Type II diabetes 

that has reported positive results 

and a parathyroid program that had 

advanced to Phase II. 

Later that month, MDRNA announced 

that it was cutting 30 percent if its staff. 

In the company’s fourth quarter and full 

year 2008 financial results release, from 

March 2009, J. Michael French, 

MDRNA CEO and president, said the 

company “has made significant strides 

in its transition from a clinical stage 

intranasal drug delivery company to an 

RNAi drug discovery company.” He 

added: “In the second half of 2008, we 

reduced headcount, terminated all legacy 

intranasal clinical programs; closed 

down idle facilities and began to sell 

excess assets. In 2009, we have renegotiated 

terms with our landlord, converted 

our capital leases into a venture loan, 

significantly reduced certain employee 

severance payments and successfully 

settled certain trade payables via negotiated 

discounts and stock issuances. 

We expect that the above restructuring, 


renegotiation and cost containment 

efforts will result in cash utilization of 

approximately $5.5 million beginning in 

the second quarter of 2009, a greater 

than 25% reduction compared to the 

fourth quarter of 2008. Additionally, we 

have entered into two non-exclusive 

license agreements with major international 

pharmaceutical companies – 

Novartis and Roche – which we believe 

validates our science, our unique intellectual 

property portfolio and our outstanding 

team. MDRNA is now poised 

to emerge as a solid drug discovery 

company focused in the cutting-edge 

area of RNAi-based therapeutics.” 

Merck – taranabant 

Merck & Co. Inc., of Whitehouse 

Station, N.J., said in late 2008 that it 

was discontinuing Phase III taranabant 

after studies showed an increased incidence 

of psychiatric events at higher 

doses. Taranabant is in the same drug 

class as Pfizer Inc.’s discontinued obesity 

product, a cannabinoid type 1 (CB1)blocker. 

The Merck obesity trials found a 

greater incidence of depression, aggression 

and other psychiatric events. 

Patients were carefully monitored, 

Merck spokeswoman Michele Rest said, 

but that regimented setting “may have 

been difficult to maintain” in the realworld 

practice of treating obesity, she 

explained. “It was after careful consideration 

that we decided that the overall 

risk-benefit profile of taranabant is not 

sufficient to seek regulatory approval 

for the treatment of obesity, and therefore 

we decided to stop further development 

of this medicine for this indication,” 

Rest said. 

Neurogen – NGD-4715 

In January 2008, Neurogen Corp., of 

Branford, Conn., said based on results of 

a follow-up component of a Phase I multiple-ascending-dose 

(MAD) study with 

NGD-4715, an MCH-1 receptor antagonist 

being investigated for the treatment 

of obesity, it will not advance the compound 

into Phase II testing at that time, 

but will consider an out-licensing deal. 

The initial phase of the MAD study used 

three-times-daily dosing for 14 days in 

healthy obese subjects exposed to a high 

caloric diet in which moderate induction 

of the liver enzyme CYP3A4 occurred, 

increasing the probability of accelerating 

metabolism of other drugs administered 

concomitantly. In addition, lipid-lowering 

effects were observed. In the follow-up 

study, CYP3A4 induction was reduced 

substantially as measured by treatment 

with midazolam, a drug sensitive to 

changes in CYP3A4 levels. However, no 

effect on lipids was observed, the company 

said. 

A month later, Neurogen cut about 70 

employees as part of a restructuring 

effort to focus on clinical candidates, 

including products for insomnia, 

cough, Parkinson’s disease, restless legs 

syndrome and obesity. 

Orexigen Therapeutics – OREX-003 

Orexigen Therapeutics Inc.’s stock took 

a nosedive in December 2008, falling 

35 percent after the company said it 

was stopping Phase II studies of weight 

gain product OREX-003 (zonisamide 

and olanzapine) to help conserve cash 

and saying good-bye to three members 

of its management team, including 

President and CEO Gary Tollefson. 

Tollefson had previously disclosed that 

he had been diagnosed with acute 

leukemia and had taken a leave of 

absence from the firm. 

Orexigen said the moves were aimed 

at conserving cash to focus resources 

on its leading obesity programs, 

including Contrave and an earlierstage 

drug, Empatic (zonisamide and 

bupropion), which is in Phase II development. 

To that end, it said it was discontinuing 

exploratory proof-of-concept 

Phase II studies of OREX-003 in 

mitigating antipsychotic-associated 

weight gain and OREX-004 (fluoxetine 

and naltrexone) in reducing symptoms 

of obsessive-compulsive disorder. But 

Orexigen said it intends to hold rights 

to those assets and might reinitiate 

those development programs in the 

future.

Pfizer – CP-945,598 

The obesity space got thinner in late 

2008 with a decision by Pfizer Inc. to 

terminate its Phase III testing of investigational 

drug CP-945,598, a 

cannabinoid type 1 (CB1)-blocker. 

Pfizer’s decision came on the heels of 

one by Merck & Co. Inc. the previous 

month to stop its obesity program, 

and another by the Sanofi-Aventis 

Group to suspend the marketing of its 

obesity drug in Europe. While Pfizer 

said it is confident in the safety of its 

compound, it cited “likely new regulatory 

requirements for approval” as one 

reason for stopping the program. 

Pfizer’s decision also was partly influenced 

by the decision of European 

regulators to call for withdrawal of 

marketing authorization for Acomplia 

(rimonabant), an obesity drug by Parisbased 

Sanofi-Aventis. At the request 

of the European Medicines Agency 

(EMEA), Sanofi agreed to temporarily 

suspend sales of its weight loss drug, 

Acomplia. Pfizer previously had indicated 

that is was planning to exit the 

area of obesity research, and CP- 

945,598 was its only obesity program 

at that time. 

Pfizer’s conversations with the FDA 

coupled with the EMEA decision on 

Acomplia ultimately led to Pfizer’s decision 

to abandon its obesity program, 

company spokeswoman Kristen Neese 

said. Pfizer would have had to perform 

additional studies for its obesity product, 

she said. The company saw that 

the regulatory hurdles had become 

“too high,” according to Neese. 

Sanofi-Aventis – Acomplia 

In October 2008, Sanofi-Aventis 

Group, of Paris, said it will comply with 

a recommendation from the European 

Medicines Agency (EMEA) to temporarily 

suspend marketing of obesity 

drug Acomplia (rimonabant) due to 

potentially higher risks and lower efficacy 

than originally anticipated. Sanofi 

said it will continue its clinical trial programs 

and remains committed to supporting 

a re-evaluation of the drug’s 

risk/benefit ratio. The drug is not 

approved in the U.S. 

Vernalis – V24343 

In May 2009, Guildford, UK-based 

Vernalis plc announced that it was 

scrapping V24343, a Phase I cannabinoid-1 

antagonist for the treatment of 

obesity. 


64 


Unfortunately, It’s a Growth Market: 


Devices Hold Top Market Billing 

Over Pharma Solutions for Obesity 

Of late, device-based therapies often 

have trumped pharmaceuticals as the 

treatment of choice when it comes to 

treating those who suffer from obesity. 

A declining interest from pharma 

after too many risky therapies, and 

less-invasive treatments on the device 

side, have led toward a stronger pushback 

into previously drug-designed 

solutions. 

It’s no secret that pharma took a 

tremendous hit in treating obesity in 

1997 when the FDA decided to pull 

Fen-Phen, an anti-obesity medication 

consisting of fenfluramine and phentermine. 

Fenfluramine, and later a 

related drug, dexfenfluramine, was 

marketed by American Home Products, 

now known as Wyeth. Reports of 

valvular heart disease and hypertension 

in users caused the FDA to order the 

drug to be pulled off the market. 

During a nearly hour-long panel meeting 

hosted by RBC Capital Markets at 

its annual Healthcare Conference at 

the Westin Times Square Hotel in New 

York in late 2008, a four-person panel 

discussed upcoming pharma solutions 

to a condition that affects two out of 

three adults. 

The panel said that while medical 

devices might be deemed a lot safer, 

pharma eventually could make a 

comeback in the obesity market. 

“The total economic cost of obesity in 

the U.S. is estimated to cost at least 

$117 billion a year,” Ken Trbovich, a 

specialty pharmaceutical analyst for 

RBC and moderator of the panel, said 

during a webcast. “And I say at least, 

because from what I can tell of that 

statistic it was generated back in the 

year 2000 and considering that obesity 

rates have continued to climb and 

the rate of inflation, one would expect 

MEDICAL DEVICES 

it’s much more than $117 billion. 

Included in that is $50 billion in avoidable 

medical expenses.” 

“The most preferred method at this 

point is gastric bypass or some form of 

surgery, whether that is laparoscopic 

or open specifically,” Trbovich said. 

“The procedures involve a three- to 

six-day hospital stay and the fact of 

the matter is that it doesn’t come 

without risk.” 

Companies such as GI Dynamics Inc., 

of Lexington, Mass., are developing 

devices that can mimic the effects of 

gastric bypass surgery on a patient’s 

metabolism, resulting in weight loss 

and remission of Type II diabetes. The 

EndoBarrier creates a mechanical 

bypass of the duodenum and proximal 

jejunum. It allows food to pass 

through the device, and allows bile 

and pancreatic enzymes to travel outside 

the liner, allowing bile and intes- 

Device and Drug Sales and Projection in the Clinical Management of Obesity, 2004-2015 

US$ millions 

7000 

6000 

5000 

4000 

3000 

2000 

1000 

0 

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 

Device Sales (US$M) 

Drug Sales (US$M) 

Source: Advanced Medical Technologies, citing MedMarket Diligencce LLC Report No. S825, “Clinical Management of Obesity.” 


66 

Balance of Drug/Device Sales in the Clinical Management of Obesity, 2004-2015 

percent 

100 

80 

60 

40 

20 

0 

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 

Source: Advanced Medical Technologies, citing MedMarket Diligencce LLC Report No. S825, “Clinical Management of Obesity 

Worldwide.” 


Device Sales (US$M) 

Drug Sales (US$M) 

Bariatric Surgical Devices and Pharmaceuticals in Obesity, Worldwide Sales and 

Projection, 2006-2015 

US$ millions 

7000 

6000 

5000 

4000 

3000 

2000 

1000 

0 

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 

Obesity 

Pharmaceuticals 

Sales 

Bariatric Surgery 

Device Sales 

Source: Advanced Medical Technologies, citing MedMarket Diagnostic Report No. S825, “Worldwide Market for the Clinical 

Management of Obesity, 2007.”

tinal hormones to travel around the 

liner without touching the food until 

later in the gut. 

Irvine, Calif.-based Allergan Inc.’s Lap- 

Band, a minimally invasive surgical 

device, also is a front-runner among 

devices that treat obesity. 

Another issue addressed is the FDA 

having much stricter standards regarding 

safety and efficacy for pharmaceutical 

approaches over device-driven 

therapies for obesity. Trbovich asked 

specifically about the differences and 

what the FDA deemed as a safe risk 

for pharmaceutical obesity treatments. 

“When patients undergo surgery there 

are surgical risks and the FDA has 

deemed that to be acceptable, even in 

instances when it might be as high as 

a 1 percent fatal consequence,” he 

said. “Clearly on the obesity side as it 

relates to pharmaceuticals, it appears 

as though there is a much higher bar. 

Is that safety bar zero? What’s an 

acceptable level of risks from your 

interactions with the [FDA]?” 

Barriers to entry into the bariatric surgery 

space are low, since even a modest 

weight loss results in resolution, 

even partially, in the associated comorbidities. 

Patient expectations are 

satisfied with a modicum of success 

because it improves their quality of life. 

The number of treatable patients 

exceed most other medical markets in 

terms of size, and even with a modest 

market share, a company should be 

able to enjoy profitable returns. There 

is enough of this giant pie to go 

around. For these reasons, as well as 

humanitarian ones, many new companies 

are developing non-surgical 

approaches to treat obesity. 

Benefits of Bariatric Surgery for 

the Morbidly Obese 

The rising of numbers of obese 

patients has been a boon for gastric 

bypass surgery, which accounts for 80 

percent of bariatric surgeries in the 

U.S. and currently total about 140,000 

procedures annually. The most common 

type of gastric bypass surgery is 

the Roux-en-Y gastric bypass, when a 

small pouch at the top of the stomach 

is created by using staples. It is then 

connected to the small intestine. 

Gastric bypass surgeries have been 

performed for 50 years. 

Several investigators at the 2008 

Obesity Society scientific meeting in 

early October reported on studies that 

demonstrated the need for increased 

activity and reduced sedentary activities 

was vital to weight loss along with 

a change in diet. 

Dale Bond at the Weight Control and 

Diabetes Research Center in the 

Warren Alpert Medical School at 

Brown University, in Providence, R.I., 

reported that bariatric surgery is quickly 

becoming a standard treatment for 

severe obesity, given its substantial 

and sustained effects on body weight, 

co-morbidities and health-related 

quality of life. His prospective study 

showed that for patients undergoing 

Roux-en-Y gastric bypass surgery, their 

level of post-operative physical activity 

affected surgical efficacy with respect 

to their weight loss and quality of life. 

Ted Adams, of the Cardiovascular 

Genetics Division at the University of 

Utah School of Medicine, in Salt Lake 

City, reported a significant reduction in 

total cancer mortality in patients following 

gastric bypass surgery, as compared 

with severely obese controls. 

These findings had been reported in 

the Aug. 23, 2007, issue of The New 

England Journal of Medicine and support 

the recommendation of reducing 

weight to lower cancer risk. 

Ramon Durazo-Arvizu, associate professor 

in the department of epidemiology 

and preventive medicine at Loyola 

University Stritch School of Medicine, 

in Maywood, Ill., reviewed data from 

his study that showed mortality from 

chronic obstructive pulmonary disease 

(COPD) in patients with extreme body 

mass indexes. COPD is the fourthleading 

cause of death in the U.S. 

Bariatric Surgery Meets Cost 

Effectiveness Standards 

At the 2009 American Society of 

Metabolic and Bariatric Surgeons, 

Matthew Hutter, of the department of 

surgery at Massachusetts General 

Hospital in Boston, compared the cost 

of obesity to the cost of weight loss 

surgery and found it to be overwhelmingly 

cost-effective as early as in the 

first year following surgery. “For 

laparoscopic surgery, all costs were 

recouped within the first two years,” 

he said. “Unfortunately, insurers don’t 

pay based on cost-effectiveness. They 

look at safety, quality, then cost – in 

that order.” 

“Medicare looks at a computation 

called quality adjusted life years 

(QALY) that includes measuring quality 

of life, life expectancy, and cost in 

order to determine payment,” Hutter 

said. “Bariatric surgery falls well below 

the Medicare threshold of QALY.” 

Bariatric Surgery Coverage Clarified 

Getting a handle on diabetes depends 

in part on getting control of one’s 

weight, and bariatric surgery is widely 

seen as one effective way to do that. 

Hence, the Nov. 17, 2008, proposal by 

the Centers for Medicare & Medicaid 

Services “to clarify its policies for 

Cost Effectiveness of 

Bariatric Surgery 

Cost of Obesity 

400,000 attributable deaths annually 

Twice as many claims for workers 

compensation 

10 times the amount of lost work days 

Cost of Weight Loss Surgery 

26 percent mortality 

$19,346 average cost 

Source: Biomedical Business & 

Technology. 


68 

Medicare coverage of bariatric surgery 

as a treatment for beneficiaries with 

Type II (or non-insulin-dependent) diabetes” 

will determine whether many 

such procedures will be paid by the 

program. 

The agency is proposing that Medicare 

will pay for bariatric surgery for Type II 

diabetics when the patient has a body 

mass index (BMI) of more than 35, a 

setting that generally is seen as reflecting 

morbid obesity. Weems said in the 

statement that the procedure is “a 

viable option for many morbidly obese 

patients who have not been successful 

with other weight loss programs.” 

The statement notes that while recent 

reports “claimed that bariatric surgery 

may be helpful for these patients, 

CMS did not find convincing medical 

evidence that bariatric surgery 

improved health outcomes for nonmorbidly 

obese individuals.” 

Study: Bariatric Surgery as Safe for 

Teens as it Is for Adults 

Reports have sounded the alarm far 

and wide about the risks associated 

with obesity to adults, children and 

teens. But some encouraging news 

was delivered for teenagers facing this 

dilemma, and the physicians who treat 

them. A study focusing on morbidly 

obese teenagers who have had lastresort 

bariatric surgery found that the 

Responses from Family 

Practitioners Regarding 

Obesity Surgery 

• Only 5 percent thought that obesity 

was best controlled by surgery. 

About 25 percent thought that the 

mortality rate was 6 percent or greater. 

Less than half thought that it would 

improve diabetes. 

Most common reason not to refer 

patient to surgeon was fear of complications 

and death. 


Technology, citing Stacie Perlman, of 

the Hospital of St. Raphael. 


procedure poses no greater risks for 

them than for adults, and in fact, they 

have a zero death rate and faster 

recovery. 

Researchers at the Robert Wood 

Johnson Medical School, in New 

Brunswick, N.J., and Cincinnati 

Children’s Hospital Medical Center 

used a large national database to 

examine nationwide trends from 1996 

to 2003 in the use of adolescent 

bariatric surgery, described as the first 

effort to compare the early post-operative 

results following bariatric surgery 

in adolescents and adults. 

The study, published in the March 

2007 issue of Archives of Pediatrics & 

Adolescent Medicine, showed that 

surgery among teens has tripled in 

recent years, increasing in the U.S. 

from an estimate of just over 200 procedures 

in 2000 to nearly 800 procedures 

in 2003. 

When researchers compared early 

post-operative results in teens and 

adults, they found that teens appear 

to handle the surgery better than 

adults. The study found that adolescents, 

ages 12 to 19, had shorter hospital 

stays and no in-hospital deaths, 

whereas a 0.2 percent mortality rate 

was recorded for adults. 

Morbidly obese adolescents are at risk 

for Type II diabetes, sleep apnea and 

heart disease but the study found they 

had significantly fewer co-morbid conditions 

prior to bariatric surgery compared 

to adults. 

The new study also compared the 

costs of surgery for adults and teens, 

finding that adolescents had lower 

hospital charges. Total hospital 

charges in 2003 for adolescents 

undergoing bariatric surgery were 

$23.6 million and for adults were $3.8 

billion. The average hospital charges 

associated with these procedures were 

15 percent lower for adolescents than 

for adults. Similar to adults, most adolescents 

had private insurance. 

Although bariatric surgery among 

adolescents has increased, it is not 

common, representing fewer than 1 

percent of the bariatric procedures 

Teen Surgeries for Obesity Are Increasing: Number of 

Bariatric Procedures for U.S. Teenagers 

number of surgeries 

900 

800 

700 

600 

500 

400 

300 

200 

100 

0 

1996 1997 1998 1999 2000 2001 2002 2003 

Source: Associated Press. “Obesity surgery triples among U.S. teens.” March 6, 2007.

performed nationwide. The study 

found that although the majority of 

surgery recipients are female, more 

male adolescents are requesting it. 

At Cincinnati Children’s, bariatric surgery 

is used as a “last resort” for morbidly 

obese teens who have tried 

unsuccessfully to lose weight through 

diet and/or exercise, the center said. 

More than 70 patients have had 

bariatric surgery at Cincinnati 

Children’s since the medical center 

began performing weight loss surgery 

in 2001. The center’s bariatric research 

program reports ongoing research 

studies sponsored by the National 

Institutes of Health, examining the 

metabolic, psychological and surgical 

outcomes of teens undergoing weight 

loss procedures. 

Economics, Diabetes and Bariatric 

Surgery 

No longer is a mechanical reduction of 

the size of the stomach, or bypassing 

part of the intestine, believed to be the 

long-term cure for obesity. Surgeons 

with the American Society for Metabolic 

and Bariatric Surgery (ASMBS), who met 

in Washington for a meeting in June 

2008, are dedicated to the treatment of 

metabolic disease and obesity, leading 

the path to better understanding of the 

root causes – and then hopefully cures 

behind this worldwide epidemic that is 

caused by a plethora of various factors 

that are still baffling. 

Previous thinking was that morbid 

obesity led to diabetes and could be 

cured by mechanically altering the alimentary 

tract, but current thinking 

proposes that it is a complex neurohormonal 

feedback to and from the 

brain and gut that allows for obesity 

and diabetes to occur, initiated by 

poor eating and exercise habits. Longterm 

studies following patients who 

had bariatric surgery 10 years to 15 

years earlier have shown that weight 

regain is a common occurrence, suggesting 

more than just a re-routing of 

the intestines can cure it. 

According to ASMBS, about 64 million 

adults in the U.S. are considered obese, 

which is associated with many other 

diseases and conditions including Type 

II diabetes, heart disease, sleep apnea, 

hypertension and cancer. While nearly 

20 million people in the U.S. have 

morbid obesity and are clinically eligible 

for surgery, only about 1 percent, 

or 205,000 in 2007, are being treated 

through bariatric surgery. 

Top Reasons Patients Don’t 

Have Bariatric Surgery 

Didn’t know enough about it (51%) 

Couldn’t afford it (38%) 

Fear of surgery (28%) 

Inadequate insurance (25%) 

No health insurance (18%) 


Technology, citing Harris Interactive. 

Number of Bariatric Surgeries in the U.S., 1993-2008 

number of surgeries 

250000 

200000 

150000 

100000 

50000 

0 

1993 

1994 

1995 

Source: American Society for Bariatric Surgery. 

Relationship Between Body Mass Index 

and Risk of Type II Diabetes Mellitus 

1996 

1997 

1998 

1999 

2000 

2001 

2002 

THE BIOWORLD AND MEDICAL DEVICE DAILY OBESITY REPORT 69 

2003 

2004 

2005 

2006 

2007 

2008

70 

An economic factor preventing many of 

the potential patients in the 20 millionperson 

pool is the cost of bariatric surgery, 

specifically the gastric bypass and 

Lap-Band procedures that can range 

from $20,000 to $30,000 and are the 

two most common procedures performed 

in the U.S. In a nationwide survey 

of 409 bariatric patients conducted 

by Harris Interactive, affordability was 

cited as the No. 2 reason patients did 

not have the surgery, second only to 

not knowing enough about it. 

One way to prod more patients into 

having the life-saving surgery is to 

make it more affordable as well as 

conquer their fears of surgery, which 

has several companies developing new 

products and procedures to meet 

these requirements. 

Other than avoiding major surgery as 

it exists today by using a less-invasive, 

less-costly, yet possibly less-effective 

method for weight loss, another way 

to skirt the economics of reimbursement 

for bariatric surgery is to position 

the procedure as a cure for diabetes as 

opposed to weight loss. 

Recent studies have shown a reversal 

of diabetes among bariatric surgery 

patients even before any weight has 

been lost. Several reports delivered at 

the ASMBS conference showed a resolution 

of diabetes after patients 

received a gastric bypass, sleeve gastrectomy 

or other novel weight loss 

procedure. Although the mechanism 

of action is still unclear, the fact that 

many bariatric procedures reverse diabetes 

almost instantly is not only 

newsworthy, but also may be lucrative. 

When it comes to paying for a surgical 

procedure, bariatric surgery is held to 

a different standard than other procedures. 

Insurance companies would 

prefer to pay for prevention of obesity 

rather than surgery. But if the surgery 

is medically necessary to treat a disease 

such as diabetes, then they may 

be more likely to pay. 


Unlike bariatric surgeons, endocrinologists 

have aligned themselves tightly 

with insurance companies and, along 

with the American Diabetes 

Association, are a formidable adversary 

to getting things done and reimbursed. 

Because of this, diabetes resolution 

was featured as a prime endpoint 

– not just weight loss – in measuring 

outcomes of bariatric procedures. 

Reimbursement for diabetes 

control may be the key to expanding 

the bariatric surgery market. 

This new line of thinking pervaded the 

meeting in regard to focusing on diabetes 

resolution, as opposed to percent 

excess weight loss (EWL), once 

considered the gold standard for 

measuring bariatric surgery outcome. 

Now diabetes resolution – often measured 

in days – has stolen the limelight 

and for several reasons, some of which 

are economic as opposed to medically 

driven. Type II diabetes affects 20 million 

Americans, or 7 percent of the 

population, and has much co-morbidity 

associated with it. Type II was once 

thought to be a disease of obesity and 

caused by excess weight, so the resulting 

reversal of diabetes, along with 

weight loss, that was found after 

bariatric surgery was not surprising. 

A landmark study in rats that showed 

an immediate reversal of diabetes 

without accompanying weight loss 

when a plastic sleeve was placed in the 

duodenum forced thought leaders to 

re-think the mechanism of diabetes 

and the role gut hormones and peptides 

may be playing in root cause of 

the disease. This study caught industry 

by surprise and several companies benefitted, 

while others may have to regroup 

based on this finding because 

they were not looking for diabetes resolution, 

but rather, weight loss. 

Revision Surgery Is a New Market 

Revisional bariatric surgery has created 

its own new sub-sector market. With 

about 20 million Americans who 

would qualify for bariatric surgery and 

only 200,000 of them actually having 

the surgery, one would think that the 

untapped remaining market pool is so 

large that growing this market sector 

through secondary applications would 

be unnecessary. 

But markets – like the gut – have a 

mind of their own, and just as diabetes 

reversal is a new market frontier, 

now revisional surgeries are creating a 

new market, albeit much smaller, but 

nonetheless, growing. 

Weight regain is a sad but significant 

problem among weight loss surgery 

patients. Many require additional surgery 

following their original surgery, 

either because of side effects or 

weight regain. This market opportunity 

has allowed some companies a way 

to enter the market earlier than they 

would have if addressing the primary 

bariatric market. 

It is estimated that about 20 percent 

(some report up to 50 percent) of all 

bariatric surgery patients will experience 

enough weight regain to require a revision 

procedure. There is controversy as 

to the reasons why people fail gastric 

bypass surgery: Two suggested theories 

are enlargement of the stoma at the 

gastrojejunostomy and dilatation of the 

gastric pouch. 

Because of potential adhesions from the 

original surgery along with the fact that 

the patient anatomy has been altered, 

most surgeons consider an endoluminal 

approach for revision surgery. Many of 

the new devices – whether targeting 

revision or primary surgery – have adopted 

an endoluminal approach because it 

is less invasive, costs less, requires shorter 

convalescence, reduces complications, 

and eventually will not need to be 

performed in an operating room, which 

also will drive the cost down. 

There are several new companies 

that fit this bill, most of which have 

products in clinical trials. In a presentation 

titled “Endoscopic Gastric

Pouch Reduction,” Dean Mikami, of 

Ohio State University, briefly described 

several companies’ products – both in 

development and on the market – 

that can perform endoluminal pouch 

reductions, often used for revisions. 

Mikami cautioned: “Initial screening of 

these patients is required to determine 

which patients will benefit from these 

procedures. Weight gain is a multi-factorial 

process; therefore, weight loss 

requires a multi-factorial approach as 

well. There is a promising future for 

revisional surgery procedures.” 

In the table “Products for Endoluminal 

Pouch Reduction,” all endoluminal 

devices that were presented at this meeting 

are listed, although each has an 

intended application – some for revisions 

following weight regain, some for primary 

treatment, and others as a bridge 

to surgery in order for the patient to 

reach a weight that is less risky for 

bariatric surgery. Each company seems to 

have a strategic target for market entry, 

but clinical outcomes will determine the 

appropriateness for use of each product 

within a specific patient population. 

Products for Endoluminal Pouch Reduction 

Many speakers at the meeting said they 

believe that eventually a combination 

of procedures and surgeries will be 

selected specifically for each patient, 

offering a personalized approach 

depending on their needs. It is interesting 

to note that most revision surgeries 

are endoluminal gastric reduction, 

while endoluminal sleeves often are 

selected for diabetes control, and 

space-fillers frequently are used for 

bridge-to-surgery purposes, even 

though there are no hard-and-fast rules 

as to which devices work best for different 

patient needs. 

USGI Medical – IOP 

San Clemente, Calif.-based USGI 

Medical Inc.’s Incisionless Operating 

Platform (IOP) could become the device 

of choice for surgeons seeking to correct 

a failed vertical banded gastroplasty 

(VBG). The IOP has been used for 

procedures designed to reduce the size 

of the stomach pouch and opening to 

the small intestine in patients who 

developed pouch or stoma dilatation 

post-Roux-en-Y gastric bypass (RYGB). 

Most physicians who treat obesity 

would agree that gastric bypass surgery 

is often an effective solution. But 

the heartbreaking truth of the procedure 

is that as many as 50 percent of 

gastric bypass patients experience 

weight regain and the dangerous comorbidities 

associated with that 

weight within a few years of the operation. 

Studies indicate that post-gastric 

bypass weight is sometimes 

regained because the stomach pouch 

and the opening to the small intestine 

(the stoma) slowly stretch out, 

enabling the patient to eat more without 

feeling full. 

A projected 30 percent to 40 percent 

of patients undergoing Roux-en-Y 

gastric bypass procedures will regain 

weight after five years, and an estimated 

250,000 gastric bypass 

patients will need revision surgery by 

2014. Invasive procedures to restore 

the anatomy to the original post-surgery 

proportions have been too complicated 

and dangerous for most 

patients, leaving them without feasible 

treatment options, but with 

much of the weight they thought 

they had lost. 

Company Product Method of Treatment Comment Market 

USGI Shapelock Endoscopic suturing 40% EWL* at 1 year; Revision 

(San Clemente, Incisionless that pleats the stomach 510(k) in 2007 

Calif.) operating using tissue anchors 

platform 

Endogastric Stomaphyx Device uses vacuum to pleat 510(k) in 2007 Revision 

Solutions with polypropylene fasteners to 

(Redmond, Wash.) reduce size of pouch and stoma 

C.R. Bard Endocinch Stoma reduction using staples; Second-generation Revision 

(Murray Hill, N.J.) 2nd generation equivalent results device in TRIM 

to band/bypass trial at Cleveland Clinic 

Safestitch N/A Intraluminal gastroplasty Filing IDE for Primary 

(St. Louis) suturing pivotal trial 

Barosense TERIS Trans-oral restrictive implant Enrolling 20-patient Primary 

(Menlo Park, Calif.) pilot study 

Satiety TOGA Flexible stapling device with 43% EWL at 1 year, Primary 

(Palo Alto, Calif.) procedure fan that controls pleat with second-generation 

Second-generation device 275-patient enrollment 

staples serosa-to-serosa for complete; results 2010 

better durability 

Notes: *EWL = excess weight loss. 

Source: Presentations at ASMBS, Biomedical Business & Technology. 


72 

Fortunately, the ROSE (Revision 

Obesity Surgery, Endolumenal) procedure 

is intended to reduce the size of 

the patient’s stomach pouch and 

stoma to about the original post-operation 

proportions to help them back 

onto the weight loss path. To perform 

ROSE, surgeons use a small, flexible 

endoscope and the IOP developed by 

USGI. The IOP (formerly called the 

EndoSurgical Operating System, or 

EOS) is inserted through the mouth 

and into the stomach pouch. The IOP 

tools are then used to grasp tissue and 

deploy suture anchors to create multiple, 

circumferential tissue folds around 

the stoma, reducing the diameter of 

the stoma. If needed, additional 

anchors are then placed in the stomach 

pouch to reduce its volume capacity. 

No cuts are made into the patient’s 

skin during the procedure. 

Making a surgical incision to reach 

areas with the abdomen always has 

been the most practical method of 

entry, or at least the most common. 

But more and more surgeons are using 

alternatives to this conventional 

method, primarily using the body’s 

natural openings as passageways that 

may be less problematic for the 

patient and providing quicker recovery 

and no observable scars. And in this 

era where speed is weighted almost as 

equally as quality, surgeons have 

struck gold using the mouth as a primary 

entry point. 

“Traditionally, patients who regained 

weight after gastric bypass had few 

options to reverse that weight gain 

because their original surgery makes 

an ‘open’ revision far too dangerous,” 

said Bluegrass Bariatrics Surgical 

Associates surgeon G. Derek Weiss. 

“The ROSE procedure helps overcome 

the past safety issues of open surgery 

with very short recovery times and 

minimal side effects. Our first patient 

lost 25 pounds in the first month following 

ROSE. We look forward to following 

all of our patients to determine 

the long term results of the procedure 


which we believe has the potential to 

dramatically impact bariatric surgery.” 

Because traditional gastric bypass revision 

surgery is so risky, a lot of insurance 

companies will not cover it, 

Weiss said. He said there is “really 

nothing to lose doing this,” because 

the ROSE procedure is a low-risk solution 

and, from what he has seen so 

far, it works. 

John Cox, vice president of sales and 

marketing for USGI, told Medical 

Device Daily that the IOP device was 

designed to offer the three fundamental 

things a physician would expect 

from such a tool – access, tools and 

instruments similar to endoscopic tool, 

and wound closure – all based on a 

platform that uses the patient’s natural 

orifices. 

The IOP device includes the TransPort 

multi-lumen operating platform, the 

g-Prox tissue grasper and approximation 

device, g-Cath tissue anchors and 

a variety of endosurgical tissue 

graspers. Its features include: access 

and visualization of the operation site; 

multiple, robust tools and instruments 

for two-handed operation; and fast, 

durable suturing for tissue apposition 

and wound closure. 

While USGI appears to be the frontrunner 

in the space so far, Cox said the 

company expects the market space to 

get crowded as more companies begin 

working on this type of solution. 

“We’re probably just the first ones 

with good data and the first ones with 

great applications and technology,” 

Cox said. As of mid-2009, the device 

had received a great amount of publicity 

and was gaining traction. IOP was 

featured in three podium sessions at 

the 2009 Society of American 

Gastroenterological and Endoscopic 

Surgeons (SAGES) scientific session in 

Phoenix. 

Because of how risky the traditional 

gastric bypass revision surgery is, not 

many patients are eager to have it 

done. This incisionless procedure, however, 

could offer a real alternative for 

those patients. “When they find out 

you can do it all through the mouth . . . 

patients jump at the chance, and surgeons 

do too,” Cox said. 

He pointed out something he says 

most people don’t realize: All of the 

visible scars and nearly all of the pain a 

patient feels during recovery from a 

surgery comes from the access part of 

the operation, not the procedure itself. 

“The benefit [of going through the 

mouth] is a quicker recovery time,” 

Frank Borao, chief of minimally invasive 

surgery and medical director at 

Monmouth Medical Center, told 

Medical Device Daily. “Patients go 

home immediately. The only thing they 

suffer from is a mild sore throat and 

that’s it.” 

C.R. Bard – EndoCinch 

C.R. Bard Inc.’s EndoCinch originally 

was approved to treat gastroesophageal 

reflux disease (GERD), but many 

bariatric surgeons are using it off-label 

as a revision tool for pouch reduction. 

The Murray Hill, N.J.-based company 

describes the EndoCinch Suturing 

System as like a tiny sewing machine. 

It is attached to the end of an endoscope, 

and sutures are placed by the 

lower esophageal sphincter (LES). Two 

stitches can be placed near each other, 

then tied together to create a pleat. 

According to the EndoCinch website, 

typically only mild sedation is required 

for the procedure (rather than general 

anesthesia). Benefits include that it 

usually is performed on an outpatient 

basis, with patients returning home 

the same day and resuming normal 

activities the day after. 

C.R. Bard is a publicly traded company 

(NYSE:BCR). It reported 2008 net sales 

of $2.452 billion, and net income of 

$416.5 million.

EndoGastric Solutions – StomaphyX 

Redmond, Wash.-based EndoGastric 

Solutions Inc.’s StomaphyX initially 

was designed to treat gastroesophageal 

reflux disorder (GERD), but 

received FDA clearance in 2007 for tissue 

ligation and approximation, and 

since then has been addressing the 

restorative bariatric surgery market. 

The StomaphyX is a pioneering device 

for natural orifice surgery (NOS). 

Without incisions and with minimal 

patient downtime, StomaphyX can be 

used to create durable large tissue 

folds in the gastrointestinal tract. 

Performed under endoscopic visualization, 

StomaphyX is introduced into the 

body transorally (through the mouth). 

As of the fall of 2009, StomaphyX had 

been used in more than 1,000 procedures 

conducted by more than 100 

surgeons in the U.S. 

In June 2008, EndoGastric Solutions 

announced the release of its next-generation 

StomaphyX device, 

StomaphyX Plus. Enhancements 

include a quick-loading fastener cartridge 

and that it can accommodate a 

larger, more standard endoscope. 

“Being able to use a standard endoscope 

permits easier clearing of the 

visual field. It also provides a higher 

resolution image for even greater precision,” 

said Dean Mikami, assistant 

professor of surgery at Ohio State 

University. 

According to Julie Ellner, laparoscopic 

surgeon at Alvarado Hospital in San 

Diego, “The stronger suction capable 

with the standard endoscope used 

with the StomaphyX Plus appears to 

result in even larger plications and 

may potentially lead to better patient 

outcomes.” 

Todd Overcash, laparoscopic surgeon 

at Munroe Regional Medical Center in 

Ocala, Fla., said the StomaphyX Plus 

made the procedure easier to perform 

and reduced his procedure time to less 

than 15 minutes. 

EndoGastric Solutions Closes on 

$21.5M E Round 

In November 2009, EndoGastric 

Solutions reported the closing of a 

$21.5 million Series E financing. The 

funding will be used to support an 

expanding commercial presence for 

the company’s NOS platform, which 

includes the EsophyX and StomaphyX 

surgical devices. The $21.5 million 

Series E Round was led by current 

investors. 

“The company is excited to receive the 

growth capital necessary to further the 

NOS market,” said Thierry Thaure, 

president and CEO of EGS. “2009 has 

been a transformational year for the 

company, as we have more than doubled 

our revenue, case volume and 

commercial employee base. With the 

scale gained through our recent 

expansion, we anticipate acceleration 

of our revenue growth in 2010.” Over 

the previous six months, EGS had 

increased its sales and marketing 

organization to support 30 territories 

nationwide, and to include a complete 

marketing, training and reimbursement 

team. 

“To date, EGS’ commercial team has 

supported over 3,000 NOS procedures 

worldwide using the company’s products,” 

said Thaure. “We aim to double 

this number in 2010. Our procedures 

are performed at over 100 hospitals in 

the U.S., where incisionless surgery 

programs and heartburn centers are 

emerging as top initiatives. By using 

our products to attract significant 

numbers of patients for incisionless 

surgery and other treatments, our hospital 

customers are improving patient 

care and growing the number of procedures 

they perform.” 

New StomaphyX Enrolls First Patients 

In August 2009, EndoGastric Solutions 

announced that the first patients had 

been enrolled in a trial to evaluate the 

use of StomaphyX to reduce weight 

regain in patients who have had Rouxen-Y 

gastric bypass surgery. According 

to the company, it is the first randomized, 

controlled, multicenter study of a 

medical device for the treatment of 

weight regain following gastric bypass 

surgery. 

The trial is expected to enroll 150 

patients at the University of Pittsburgh 

Medical Center (UPMC) and the Ohio 

State University Medical Center. It will 

compare StomaphyX to a sham procedure. 

The primary endpoint is excess 

weight loss at twelve months. 

EndoGastric Solutions expects the 

study will be completed in July 2011, 

at which time the company hopes to 

gain a bariatric clearance for the 

device. 

Carol A. McCloskey, assistant professor 

of surgery at UPMC and co-investigator 

of the study said their gastric 

bypass patients were very enthusiastic 

about the StomaphyX procedure. 

“The StomaphyX study’s procedural 

goal is to reduce the size of an 

enlarged pouch in patients who originally 

lost significant weight following 

gastric bypass but then regained some 

of it back. Many patients may find the 

transoral, incisionless StomaphyX procedure 

appealing when compared to a 

standard surgical revision because it 

offers minimal post operative pain, 

faster recovery time, and no scarring,” 

she said in a release. 

EGS Raises $30M in Financing 

In August 2007, EndoGastric Solutions 

announced that it had completed a 

$30 million Series D round of private 

financing. It was led by DeNovo 

Ventures, and other investors participating 

included Chicago Growth 

Partners, MPM Capital, Advanced 

Technology Ventures, Foundation 

Medical Partners and Oakwood 

Medical Investors. 

Adjustable Gastric Bands Fill Need, 

Face Market Risk 

Gastric banding and gastric bypass are 

the most commonly performed surgical 

procedures on obese patients for 


74 

weight loss. Together, they amounted 

to about 300,000 procedures in 2008. 

There are close to 20 million obese candidates 

for bariatric surgery in the U.S. 

Restrictive operations that make the 

stomach smaller, such as adjustable 

gastric banding (gastroplasty procedure), 

create a full feeling after a small 

meal. Larry Biegelsen, a med-tech analyst 

for Wachovia Capital Markets, in a 

research note said that Wachovia 

expects the global banding market to 

reach $1 billion in 2011, up from $320 

million in 2007. 

Factors that should help the U.S. market 

growth stay robust, according to 

Biegelsen’s research note, include the 

“vastly underpenetrated” U.S. population 

of bariatric surgery candidates. 

Only 1 percent of the 20 million 

Americans who would qualify for 

bariatric surgery have it done. 

The note said that increased penetration 

into the obese population sector 

should be driven by increased awareness 

of surgical options for patients 

through Allergan Inc.’s and Johnson & 

Johnson’s increased marketing efforts; 

increased insurance coverage; the 

potential for expanded indications; 

and recent positive outcomes data. 

But a changing trend in bariatric surgery 

in Europe could spell trouble for 

the U.S. gastric banding market, 

Biegelsen noted. “Our contacts indicate 

that gastric banding is falling out 

of favor in key markets, including 

Germany and Switzerland, due to 

long-term complications,” Biegelsen 

said. “The Lap-Band has been available 

in [Europe] about 10 years longer 

than in the U.S., and we understand 

that complications that emerge at four 

to five years post-op have discouraged 

some [European] surgeons from continued 

use. Surgeons are moving to 

more invasive procedures including 

gastric bypass, gastric sleeving, and 

duodenal switch. “This is the largest 

risk to our U.S. banding forecasts, 


given that U.S. surgeons are approaching 

five-year follow-up over the next 

few years.” 

Biegelsen said that gastric sleeving 

might emerge as a threat to the banding 

market in when it receives insurance 

coverage. While gastric sleeving 

is more invasive than banding and targeted 

for the extremely obese, U.S. 

and European doctors are optimistic 

about it because of its improved 

weight loss profile of 40 percent to 60 

percent at one to two years, Biegelsen 

said. Gastric sleeving also has lower 

comparable side effects to banding, 

he noted. 

Allergan – Lap-Band 

Allergan Inc., of Irvine, Calif., markets 

the Lap-Band Adjustable Gastric 

Banding System for obesity. Its name 

comes from the minimally invasive surgical 

technique used – laparoscopy – 

and the silicone gastric band. The 

band uses a silicone ring filled with 

saline placed around the top of the 

upper part of a patient’s stomach, 

which then creates a smaller stomach 

pouch. It helps patients control their 

weight and lose weight by reducing 

the amount of food that the stomach 

can hold at one time and by making 

patients feel fuller sooner. Allergan’s 

Omniform technology allows the Lap- 

Band System to maintain controlled, 

even and round inflation throughout the 

adjustment range of the band. It was the 

first adjustable medical device for individualized 

weight loss and the first minimally 

invasive surgical approach 

approved in the U.S. by the FDA. 

According to the product website, 

patients using the Lap-Band System 

may see weight loss of two to three 

pounds a week in the first year, but 

about one pound per week is more 

likely. As time goes by, the amount of 

weight lost is usually less. Many 

patients lose weight more quickly with 

gastric bypass surgery, but at three 

years, Lap-Band users often show a 

comparable amount of weight loss. 

According to the Lap-Band website, 

the costs of the procedure (including 

the facility, surgeon and anesthesiologist) 

range from $12,000 to $25,000. 

After the first year, there may be additional 

costs for follow-up visits that 

range from $35 to $200 each. Many 

health plans now cover Lap-Band surgery, 

including Medicare, and 

Medicaid in some states. Insurance 

companies that either partially or fully 

cover Lap-Band surgery include Aetna, 

Blue Cross in some states, Humana 

and United Healthcare, among others. 

The Lap-Band System was introduced 

outside of the U.S. in July 1994 (to be 

used by surgeons trained at Allerganapproved 

centers). U.S. clinical trials 

started in June 1995, and the FDA 

approved the Lap-Band for general 

use in June 2001. More than 500,000 

Lap-Band System devices have been 

distributed worldwide, and it is the 

No. 1 selling adjustable gastric band 

for weight loss worldwide, according 

to the company. 

The Lap-Band is for use by people 18 

years and older who are at least 100 

pounds overweight (or twice their 

ideal weight), or who have a BMI of 40 

or higher (or 35 or higher, if co-morbidities 

such as Type II diabetes exist). 

Allergan also has introduced the Lap- 

Band AP System to extend the performance 

of the original Lap-Band 

System. The next-generation system, 

introduced in the U.S. in 2007, uses 

patented Omniform technology, which 

is designed to minimize the potential 

for leaks due to unwanted creases or 

folds (called crease-fold failure). 

According to Allergan, Omniform introduces 

a 360 degree inflation area that 

“evenly distributes pressure for complete 

coverage of stomach anatomy.” 

The product website lists a number of 

advantages of Lap-Band. It is a minimally 

invasive surgical approach that 

requires no intestinal re-routing, cutting 

or stapling of the stomach wall or

owel (as does gastric bypass surgery). 

The surgery is generally outpatient, 

and patients typically return 

to work and normal activities within a 

week. Allergan reports that Lap-Band 

has a ten times lower short-term mortality 

rate than gastric bypass and also 

a low risk of post-surgical nutritional 

deficiencies that often are associated 

with gastric bypass surgery. Although 

it is intended to be a long-term treatment, 

the Lap-Band can be removed if 

necessary. 

Allergan’s other products include 

Botox (onabotulinumtoxinA), Restasis 

(cyclosporine ophthalmic emulsion), 

Lumigan (bimatoprost ophthalmic 

solution) and the Juvederm family of 

dermal fillers. The Lap-Band also is in 

clinicals in the U.S. to lower body mass 

index and for an adolescent indication. 

Allergan’s other products in development 

for obesity include the Orbera 

Intragastric Balloon System (in clinicals 

in the U.S.; approved in Europe, 

Canada and South America) and 

EasyBand (in feasibility). 

Study Shows Lap-Band Lowers Co- 

Morbidity Risk in Teens 

In July 2009, a study of obese 

teenagers showed that the Lap-Band 

lowers co-morbidity risk in teens, as it 

not only helps them achieve significant 

weight loss but also can improve and 

even reverse metabolic syndrome, 

reducing their risk for cardiovascular 

disease and diabetes. 

The study was led by Ilene Fennoy, 

Jeffrey Zitsman, and colleagues at 

NewYork-Presbyterian Morgan Stanley 

Children’s Hospital and Columbia 

University Medical Center, of New 

York, and presented at the annual 

Endocrine Society meeting in 

Washington. Fennoy and her colleagues 

followed 24 morbidly obese 

adolescents between the ages of 14 

and 17 who underwent the Lap-Band 

procedure. The study participants 

either had a body mass index (BMI) of 

greater than 40, or greater than 35 if 

already suffering from diabetes or 

obesity-related illnesses. Six months 

after surgery, they noted a significant 

drop in participants’ BMI, waist circumference, 

and blood levels of Creactive 

protein. These indicators continued 

to improve among the 12 

patients being followed up at the oneyear 

point, the authors noted. 

Allergan’s Lap-Band is currently under 

FDA review for use in adolescents in 

the U.S. 

Lap-Band AP System Seen Aiding 

Diabetes Fight 

Also in July, Allergan said its Lap-Band 

AP System became the first device to 

receive official European approval for 

weight loss that leads to improvement 

or remission of Type II diabetes. 

Type II diabetes has reached pandemic 

proportions, and the risk of developing 

Type II diabetes is increased up to 

10 times in people who are obese. 

Obesity is defined as having a BMI of 

30 or greater. The UK has the fastestgrowing 

rate of obesity in the developed 

world, with the number of obese 

people with Type II diabetes estimated 

to have increased by 1 million over the 

past five years. Allergan said recent 

estimates are that 10 percent of all 

National Health Service (NHS) spending 

goes to diabetes. That equates to 

£9 billion per year. 

“Type II diabetes is becoming an 

increasing problem as the prevalence 

of severe or morbid obesity in the population 

rises,” said Dr. Jonathan 

Pinkney, consultant senior lecturer and 

diabetologist. “The proven success of 

gastric banding procedures in these 

patients is timely and provides us with 

a powerful alternative to tackle the 

morbidity and mortality associated 

with diabesity,” he said. Diabesity is a 

term coined by Shape Up America to 

define the correlation between diabetes 

and obesity. 

Pinkney added, “The gastric banding 

procedure is a highly effective option 

for selected obese patients who are 

failing to reduce their weight through 

traditional weight-reduction methods. 

The recognition of a device such as the 

Lap-Band AP System by European 

health authorities is an important 

advance for the medical community 

and obese patients in our efforts to 

effectively manage Type II diabetes.” 

U.S. Was Skeptical of Lap-Band at 

the Start 

The Lap-Band has garnered the majority 

of market share in Europe, but 

“U.S. surgeons were skeptical when it 

was first cleared by the FDA in 2001, 

citing poor weight loss and band slippage 

as the most common reasons,” 

according to David Provost, of Dallasbased 

Southwestern Medical Center in 

a presentation at the 2007 American 

Society for Bariatric Surgery meeting, 

“Laparoscopic Adjustable Gastric 

Banding for Morbid Obesity: The U.S. 

Experience.” However, “now it has 

garnered over 20 percent of all 

bariatric surgeries performed in the 

U.S., due to improved outcomes and a 

marked reduction in complications.” 

In a meta-analysis he performed that 

included 4,937 patients, he found that 

“excess weight loss using the Lap- 

Band ranged from 32 percent to 62 

percent at one year; 35 percent to 61 

percent at two years; 39 percent to 66 

percent at three years, and remained 

around 55 percent from four years 

on.” He concluded that “the Lap-Band 

provides excellent weight loss, co-morbidity 

improvement, and 55 percent 

excess weight loss out to four years – 

the same as is seen with gastric 

bypass.” Because the long-term success 

rate of the band is similar to that 

of gastric bypass but without the permanency, 

market shares have shifted, 

with about 70 percent (down from 85 

percent) of the surgeries being Rouxen-Y, 

25 percent Lap-Band and the 

remaining 5 percent consisting of the 

duodenal switch, gastrectomy sleeve 

and other procedures. 


76 

All of these procedures require varying 

degrees of surgery and each bears its 

own set of morbidities, or side effects 

coupled with its individual benefit profile. 

With the exception of totally noncompliant 

patients, each procedure 

will produce some amount of weight 

loss; and in tandem with lifestyle 

changes, the amount can be dramatic. 

“Obesity carries with it a two to three 

times mortality rate over a normalweight 

individual,” said Luca Busetto, 

of Terapia Medica e Chirurgic Obesita 

in Padova, Italy, in a presentation titled 

“Reduction of 5 Years Total Mortality 

in Morbid Obese Patients Treated with 

Laparoscopic Adjustable Gastric 

Banding.” 

He accumulated data on 4,732 patients 

with BMIs of more than 40 and divided 

them into two matched groups: one 

receiving medical management and 

one group receiving the Lap-Band – 

and then looked at each group’s longterm 

mortality in order to compare 

medical management with the least 

invasive surgical procedure. “The Lap- 

Band patients peaked at two years with 

an excess weight loss of 42 percent, but 

had a reduction of 60 percent in total 

mortality compared to those who were 

medically managed,” he said. 

There is evidence that bariatric surgery 

also improves obesity patients’ 

mental outlooks on life. A poster 

presentation, “Quality of Life After 

Gastric Banding in a Multidisciplinary 

Institution” by Tony T. Brancatisano, 

of the Sydney-based Institute of 

Weight Control, studied 945 obese 

patients pre- and post-Lap-Band and 

found that “pre-operatively the 

patients indicated that they had 

severe disabilities with moderate 

depression. Even a moderate weight 

loss provided a dramatic improvement 

in quality of life.” 

Ethicon Endo-Surgery – Realize 

Ethicon Endo-Surgery Inc., of 

Cincinnati, in October 2007 reported 


FDA approval for its Realize Adjustable 

Gastric Band, indicated for people 

with a body mass index (BMI) of at 

least 40 kg/m2, or a BMI of at least 35 

kg/m2 with one or more co-morbid 

conditions. It is for use in morbidly 

obese adult patients who have failed 

more conservative weight-reduction 

alternatives, such as supervised diet, 

exercise and behavior modification 

programs, the company said. The 

company reported submitting an 

application for FDA approval of the 

band in April 2007. 

Ethicon, a business of Johnson & 

Johnson, of New Brunswick, N.J., was 

the second company to enter the 

U.S.’s gastric banding market. It joined 

Irvine, Calif.-based Allergan Inc. in an 

effort to entice morbidly obese 

patients to use gastric banding, a lessinvasive 

alternative to bariatric surgery. 

The FDA cleared Allergan’s Lap-Band 

in June 2001. 

In the procedure with the Realize 

Band, a soft, adjustable silicone band 

is wrapped around the stomach to create 

two chambers – a small upper 

stomach with a narrow opening to the 

lower stomach. After the procedure, 

the upper stomach is able to hold only 

about four ounces of food, which limits 

food intake, makes patients feel full 

faster and longer, and slows digestion. 

Once the band is in place, surgeons 

attach the Realize Injection Port to the 

abdominal wall underneath the skin 

using the Realize Injection Port Applier, 

which can be done in less than a 

minute, according to the company. 

The Realize Injection Port allows doctors 

to inject or remove saline to tighten 

or loosen the band. The tighter the 

band, the more quickly the upper 

stomach fills up and the less food a 

person can eat. Adjustments are made 

periodically based on the patient’s 

individual needs, the company said. 

In effect, the Realize “works like the 

Lap-Band,” Ed Phillips, principal inves- 

tigator in the multi-center U.S. trial 

with the Realize Band, told Medical 

Device Daily when the product gained 

approval. 

Phillips, director of the Center for 

Minimally Invasive and Bariatric 

Surgery at Cedars-Sinai Medical 

Center in Los Angeles, said comparing 

the two gastric bands is a bit like comparing 

a Ford to a Chevy, with slight 

differences in the way the two devices 

are constructed. 

In the Realize Band trial, the 228 

patients who completed the three-year 

trial lost an average of 42.8 percent of 

excess body weight, 35 percent lost at 

least 50 percent of excess body weight, 

and 10.5 percent lost 75 percent or 

more of excess body weight, Ethicon 

said. The most commonly reported 

adverse events after surgery during the 

trial were nausea, vomiting, constipation 

and gastro-esophageal reflux. 

Nine patients, or 3.3 percent, experienced 

a serious adverse event related 

to Realize Band use that was considered 

“unanticipated.” 

“It takes about three years to lose the 

maximum weight [with gastric banding],” 

Phillips said, compared to gastric 

bypass, which takes about 18 

months. He added that the gastric 

band is a “tool” that also requires 

patient compliance. “This rigorous 

clinical trial showed patients using the 

Realize Band experienced significant 

weight loss within the first year, which 

remained steady over three years,” 

Phillips said. “This procedure, combined 

with the proper support system 

and a commitment to dietary and 

lifestyle changes after surgery helped 

these patients achieve long-term 

weight loss and improvement in many 

obesity-related conditions.” 

In the trial, patients reported improvements 

in various quality-of-life factors, 

including better general health one 

year after surgery, the company noted. 

Significant improvements in vitality,

mental health and social functioning 

were reported at three years after surgery, 

along with reduction in bodily 

pain and increased ability to complete 

daily activities. 

The product is marketed outside the 

U.S. under the name Swedish 

Adjustable Gastric Band, where it has 

been sold since 1996 and used on 

more than 100,00 patients worldwide 

to help manage their weight. 

Gastric Bypass vs. Gastric Band 

The most common bariatric procedures 

performed in the U.S. are gastric bypass 

and the gastric band, which typically 

are performed laparoscopically. 

These two procedures were compared 

in a 2007 study conducted by Nancy 

Puzziferri, assistant professor in the 

division of GI/endocrine surgery at the 

University of Texas Southwestern 

Medical Center in Dallas. 

It used non-randomized and retrospective 

data from a study comprising 

1,100 gastric bypass patients and 633 

lap-banding patients. The selection of 

bypass vs. band was based on the 

patient/surgeon discussion. Puzziferri 

reported that for patients undergoing 

the gastric bypass procedure, the initial 

weight loss occurred faster and the 

average weight loss was greater after 

24 months, as compared to gastric 

banding. 

Success was defined as a loss of at 

least 40 percent of a patient’s weight. 

There was a higher attrition rate 

among gastric bypass patients than 

gastric band patients. Puzziferri also 

noted the number of lap-banding procedures 

is increasing. 

David Provost, also from the University 

of Texas Southwestern Medical Center, 

reviewed the criteria for selecting a 

bariatric surgical procedure for morbidly 

obese patients. The procedures 

included laparoscopic adjusted gastric 

banding (LAGB), gastric bypass (GB) 

and biliary pancreatic diversion (BPD), 

although he rarely performs the latter 

procedure, which is accompanied by 

significant malabsorption of nutrients. 

Key considerations in selecting candidates 

for bariatric surgery are the 

potential for weight loss, co-morbidity 

resolution (e.g., hypertension, diabetes, 

gastroesophageal reflux 

disease, asthma and sleep apnea), 

complications and mortality, along 

with the patient characteristics, such 

as age, gender and surgical preference. 

He reported similar success in weight 

loss and co-morbidity resolution for 

patients having either LAGB or GB 

procedures over a two-year period, 

but the rate of weight loss was faster 

with LAGB patients along with a higher 

risk of life-threatening complications 

from this procedure. GB is easier 

to surgically reverse than LAGB, but 

the patient should consider that these 

procedures are permanent. 

Provost also compared the Roux-en-Y 

gastric bypass (RYGB) open surgical procedure 

to LAGB laparoscopic gastric procedure, 

as shown in the table 

“Invasiveness of Roux-en-Y Gastric 

Bypass vs. Laproscopic Gastric Banding.” 

Study Explores Costs of Gastric 

Bypass and Gastric Banding 

Bariatric surgery has been shown in 

clinical trials to result in substantial 

weight loss and resolution of some 

co-morbidities such as diabetes, but 

associated with important costs and 

consequences. For instance, because 

of its high cost – $15,000 to 

$20,000 – many insurers do not 

cover the surgery. 

A 2006 study conducted by Derek 

Brown and Eric Finkelstein of RTI 

International, of Research Triangle 

Park, N.C., explored whether savings 

resulting from improved health following 

two bariatric procedures, gastric 

bypass and gastric banding, offset the 

cost of the procedures. The results 

were mixed. 

The authors looked at the differences in 

mean quarterly costs, inpatient hospitalization 

rates and the number of prescription 

drug payments before and 

after surgery, using medical claims for 

the procedures from more than 100 

insurance plans during the period of 

2001 to 2004. The data showed that 

both gastric banding and gastric bypass 

achieved modest reductions in prescription 

drug use and post-surgical costs. 

However, the net effect on costs was 

different between the two procedures. 

Gastric banding resulted in a mean 

total savings of about $1,400 per year. 

On average, no savings were achieved 

from gastric bypass because of 

increased hospitalization rates resulting 

from surgical complications. The 

study concluded that for payers to 

Invasiveness of Roux-en-Y Gastric Bypass vs. 

Laproscopic Adjustable Gastric Banding 

RYGB LAGB 

Impact on Considerable Minimal 

GI tract 2 anastomoses, Minimal trauma 

stomach division No effect on 

Decreased micro- micronutrient absorption 

nutrient absorption 

Reversible? No Yes 

Foreign body? No Yes 

Possible slippage, leaks, 

infection 



78 

achieve savings from gastric bypass, it 

is critical to reduce the incidence of 

adverse events of this procedure. 

Less-Invasive Products Are New 

Market Segments for Bariatric 

Surgery 

About 20 million Americans would 

qualify for insurance coverage for 

bariatric surgery, but only 200,000, or 1 

percent, have it done. Many patients 

fear available bariatric surgery options 

because the operation dramatically and 

permanently alters the alimentary tract 

anatomy and can be associated with 

potential risks and side effects following 

the surgery. 

In an effort to reach the remaining 99 

percent of obese patients who are not 

receiving the life-saving surgery, companies 

are scrambling to help these 

patients by enticing them with less 

invasive, albeit not quite as effective, 

procedures – a trade-off that appears to 

be gaining popularity if the Lap-Band 

from Allergan Inc. is any indication. In 

addition to the less-invasive, reversible, 

gastric bands, other novel approaches 

are coming into play as well. 

Historically, bariatric surgery consisted 

of three main types: the Roux-en-Y procedure, 

also called the gastric bypass, 

which is both restrictive and malabsorptive; 

the duodenal switch (mostly malabsorptive); 

and the Lap-Band (restrictive 

only). Although the first two types 

permanently alter the alimentary anatomy, 

bands only restrict the gastric 

pouch and can be removed or adjusted, 

leaving the anatomy intact. 

One can no longer count only the 

200,000-plus bariatric surgery procedures 

performed annually as being “the 

bariatric surgery market.” As the 

American obesity epidemic grows, so 

does the growth in new technologies 

to address not only the current population 

of patients seeking surgical assistance, 

but also those who qualify but 

never enter a doctor’s office for fear of 

surgery. 


Both adjunctive technologies for better 

patient outcomes using current 

surgical approaches and a host of lessinvasive 

innovative products that 

address the obese millions afraid to go 

under the knife were presented during 

the 26th annual meeting of the 

American Society of Metabolic and 

Bariatric Surgery, held in Dallas in June 

2009. There was a flurry of activity 

among the exhibitors to showcase 

improvements and innovations in 

technologies that can help the more 

than 20 million obese Americans. 

After closely following the hundreds 

of thousands of post-bariatric surgery 

patients, market segmentation within 

the bariatric surgery space has 

evolved. 

For most morbidly obese patients, the 

now-standardized surgical procedures 

will be adequate. Some patients, however, 

have more specific needs, which 

fueled much discussion at the meeting. 

Until recently, the only options for 

bariatric patients were which type of 

surgery: gastric bypass, lap-banding, 

duodenal switch, or the newly revived 

gastrectomy sleeve. Each has its benefits 

as well as shortcomings. 

For the first time, innovative devices 

now in human clinical trials offer a 

menu of products from which the surgeon 

and patients can select. These 

new devices can be categorized as 

being more suitable for specific groups 

of bariatric patients, such as: less-invasive 

primary weight loss, revisions for 

weight regain, bridge to surgery, metabolic/diabetic 

surgery, combinations, or 

what some predict will become cosmetic 

or elective procedures. 

Minimally Invasive Procedures 

GI Dynamics – EndoBarrier 

GI Dynamics Inc., of Lexington, Mass., 

is a developer of non-surgical, endoscopic 

approaches for the treatment of 

Type II diabetes and obesity. Its 

EndoBarrier Gastrointestinal Liner cre- 

ates a physical barrier that lines the 

small intestine just below the pylorus 

to keep food from coming in contact 

with the intestinal wall. Physicians 

believe this may alter the activation of 

hormonal signals that originate in the 

intestine, and may mimic the effects of 

a Roux-en-Y gastric bypass procedure. 

However, the EndoBarrier procedure is 

done without the risks associated with 

highly invasive surgical procedures. 

The EndoBarrier is placed and 

removed endoscopically (via the 

mouth) without the need for surgical 

intervention or alteration of the 

patient’s anatomy. In addition, it 

allows treatment to be individualized 

for patients. 

According to GI Dynamics’ website, 

other advantages of EndoBarrier 

include: its facilitation of weight loss, 

the reduction or elimination of other 

co-morbidities, possibility of elimination 

of other therapies for the treatment 

of Type II diabetes and obesity, it 

is placed in a nonsurgical procedure, 

and it is reversible. 

Clinical trials involving more than 250 

patients have demonstrated the dramatic 

weight loss and diabetes 

improvement achieved with the 

EndoBarrier Gastrointestinal Liner. 

Trials have been conducted in South 

America, Europe and the U.S. Weight 

loss is enhanced when the EndoBarrier 

GL, the flagship product of the company, 

is combined with the 

EndoBarrier Flow Restrictor. 

GI Dynamics received the CE mark for 

the EndoBarrier in January 2009 and 

plans to launch the product in Europe 

in 2010 for obese diabetic patients. 

Stu Randle, GI Dynamics CEO, said 

that the company hopes to have FDA 

approval within the next five years, but 

would not give a more firm date of 

when the company would launch the 

device in the U.S. 

When and if the device gains approval, 

it enters into a plethora of treatments

for Type II diabetes. The company says 

that the EndoBarrier differs because it 

is less invasive than other treatments 

and is placed in the GI tract endoscopically 

(via the mouth) to create a barrier 

between food and the wall of the 

intestine. The company said that this 

method would prevent food from 

coming into contact with the intestinal 

wall and could alter the activation of 

hormonal signals that originate in the 

intestine. 

“Based on the data we have seen to 

date, we believe EndoBarrier, as part of 

a multidisciplinary approach, has the 

potential to dramatically change the 

treatment paradigm for Type II diabetes 

and weight problems due to its unique 

profile as a non-surgical and non-pharmaceutical 

treatment option,” said 

Randle. “Notably,” he said, “EndoBarrier 

may provide the benefits of gastric 

bypass surgery without the complications 

and risks associated with a highly 

invasive procedure, and unlike traditional 

pharmaceutical approaches, our 

implantable device removes the burden 

of dose regimen compliance from the 

patient.” 

A growing body of preclinical and clinical 

evidence supports the potential for 

EndoBarrier Gastrointestinal Liner to 

dramatically change the treatment 

landscape for people living with Type II 

diabetes, obese people at risk for Type 

II diabetes and people with severe 

weight problems, he added. 

Support for the EndoBarrier, which is 

poised to become a platform technology, 

has been overwhelming, according 


Study Shows EndoBarrier Helps 

Diabetics Achieve Normalization 

In November 2009, GI Dynamics 

reported data which demonstrate that 

obese patients with uncontrolled Type 

II diabetes using the EndoBarrier gastrointestinal 

liner achieved near normalization 

of glycemic control in just 

one week, as compared to a sham 

control group. In addition, patients 

treated with EndoBarrier achieved a 

mean reduction of 2.4 percent in 

HbA1c glucose levels versus 0.8 percent 

for the sham arm at 24 weeks. 

Patients treated with EndoBarrier also 

achieved reductions in other diabetic 

factors including fasting blood glucose 

and weight. 

GI Gains Traction for EndoBarrier 

with Favorable Study Results 

GI Dynamics’ attempts for regulatory 

approval for its EndoBarrier gastrointestinal 

liner received a much-needed 

boost in November 2009 with the 

release of results of a European 

weight-loss study targeting the device. 

The device was evaluated for its safety 

and efficacy for pre-surgical weight 

loss treatment, along with a positive 

effect on glucose homeostasis in morbidly 

obese patients with Type II diabetes 

mellitus. Study data were published 

in the Annals of Surgery. 

“The company is very pleased with 

these results,” Stuart Randle, GI 

Dynamics CEO, told Medical Device 

Daily. “The results seem to coincide 

with other trials that we have had in 

South America. This was the first 

European clinical weight loss study conducted 

with the EndoBarrier, and since 

then the EndoBarrier has been successfully 

implanted in more than 250 

patients. As GI Dynamics has expanded 

the clinical development program for 

EndoBarrier in patients with obesity and 

Type II diabetes, we have continued to 

see impressive results.” 

In a recent multi-center, randomized 

clinical trial, 41 patients were enrolled 

and 37 patients were treated. Twentysix 

patients received the EndoBarrier 

and 11 were in the diet control group. 

The EndoBarrier was implanted for 12 

weeks. Three patients kept the device 

implanted for 24 weeks. Patients in 

both the EndoBarrier and diet control 

groups followed the same diet during 

the study period. Starting average 

weight for these two groups was simi- 

lar with 142.5 kg (314.2 lbs) for 

EndoBarrier patients versus 137.5 kg 

(303.2 lbs) for control group patients, 

and body mass index (BMI) of 48.9 vs. 

49.2, respectively. 

Mean excess weight loss (EWL) 

achieved after 12 weeks was 19.0 percent 

for EndoBarrier patients versus 

6.9 percent for control patients 

(p

GI Dynamics, told Medical Device Daily 

from the floors of the International 

Federation for the Surgery of Obesity 

and Metabolic Disorders annual meeting 

in Paris. “When we combine the 

flow restrictor with the EndoBarrier we 

see nearly double the weight loss.” 

A clinical study regarding the effectiveness 

of EndoBarrier with Flow 

Restrictor demonstrated the substantially 

enhanced weight loss benefits of 

combining the company’s EndoBarrier 

gastrointestinal liner with a new 

EndoBarrier Flow Restrictor. In this initial, 

single-center study of 10 morbidly 

obese people (body mass index 

between 35.8 and 47.8), participants 

achieved the following results over a 

12-week period during which the 

device was implanted (median values 

reported): 

• Percent Excess Weight Loss (%EWL): 

39.6 percent 

• Weight Loss: 36.7 pounds (16.7 kilograms) 

• Percent Total Body Weight Loss 

(%TBWL): 15.4 percent 

80 

All 10 patients completed the 12week 

study. The most common side 

effects included mild to moderate 

abdominal pain, nausea and vomiting. 

“We have had significant clinical 

experience with the EndoBarrier at 

our obesity management center, and 

even when assessed relative to invasive 

and other noninvasive procedures, 

we believe the EndoBarrier 

platform represents a much needed 

new approach to reducing weight and 

improving blood sugar control in 

obese patients and patients at risk for 

serious metabolic disease,” said 

Manoel Galvao Neto, a lead investigator 

for the study. 

“In particular, we are excited about 

the new data emerging from our 

ongoing clinical study in people living 

with Type II diabetes and the notable 

impact EndoBarrier appears to have on 

blood sugar control. We look forward 


to sharing these data later this year 

upon completion of the trial,” he said. 

The EndoBarrier Flow Restrictor provides 

an adjustable restriction at the 

outlet of the stomach and is designed 

to delay gastric emptying, an additional 

mechanism which adds to the therapeutic 

effects of the liner. 

These latest data suggest that the combination 

of the EndoBarrier gastrointestinal 

liner with the EndoBarrier Flow 

Restrictor could enhance the effectiveness 

of the liner by nearly doubling the 

amount of weight loss achieved by 

using the liner alone. The clinical data is 

consistent with previously reported preclinical 

data from the company assessing 

the combination of devices in a 

porcine model. 

GI Raises $15M More in ‘C’ Round, 

Brings Total to $45M 

GI Dynamics said in February 2009 

that it closed an additional $15 million 

in Series C financing. With this 

additional funding, GI has closed a 

total of $45 million in Series C financing, 

bringing the total raised by the 

company since its inception to $61 

million. 

GI said it would use proceeds from this 

financing to advance the clinical development 

of its EndoBarrier gastrointestinal 

liner and EndoBarrier platform 

of devices for the treatment of metabolic 

disorders, including Type II diabetes 

and obesity. Participants in the 

round included all of GI Dynamics’ current 

institutional investors: Advanced 

Technology Ventures, Catalyst Health 

Ventures, Cutlass Capital, Domain 

Associates, Johnson & Johnson 

Development Corp. and Polaris 

Venture Partners. 

“Attracting additional capital from 

leading investors and pharmaceutical 

organizations in this market is a testament 

to the progress we have made 

over the last several years and the significant 

commercial potential of our 

EndoBarrier gastrointestinal liner to 

treat metabolic disorders,” said CEO 

Stuart Randle. “This funding further 

strengthens our ability to aggressively 

advance EndoBarrier into the next 

stage of clinical trials for the treatment 

of Type II diabetes and obesity, while 

continuing to develop additional products 

for the treatment of metabolic 

disorders based on the EndoBarrier 

intellectual property.” 

GI Dynamics Receives CE Mark 

Along with ISO Certification 

GI Dynamics said in January 2009 that 

it received ISO 13485:2003 certification 

for its Lexington, Mass., facility, along 

with CE-mark approval for the 

EndoBarrier. ISO 13485: 2003 is an 

international standard that specifies a 

quality management system for medical 

devices and related services. 

“We are very pleased to . . . have 

received both the ISO certification and 

the CE mark approval, which are important 

milestones as we continue to 

develop the EndoBarrier and lay the 

groundwork for future commercialization 

of the product,” said CEO Stuart 

Randle. “Promising data continue to 

emerge from our clinical development 

programs in both obesity and Type II 

diabetes.” 

Satiety – TOGA 

Satiety – the feeling of fullness and disappearance 

of appetite after a meal – is 

exactly what Palo Alto, Calif.-based 

Satiety Inc. wants to help patients 

achieve with its transoral gastroplasty 

(TOGA) procedure. Satiety’s TOGA system 

– a transoral restrictive operation 

for obesity – is touted by the company 

as a much less invasive procedure as 

compared to bariatric surgery. It is in a 

multi-center pivotal trial in the U.S. It 

was granted CE Mark, but is not yet 

available for sale in Europe, where it is 

undergoing a pivotal clinical study. 

Here’s how it works: Patients are given 

general anesthesia, and the TOGA 

Sleeve Stapler is inserted into the

stomach via the mouth. A retraction 

device is used to spread the stomach 

tissue. The device then uses suction to 

collect tissue from the anterior and posterior 

of the stomach. The stomach is 

stapled, creating a sleeve at the entry of 

the stomach. Then, the TOGA 

Restrictor is inserted, which narrows 

the bottom of the sleeve. The pouch 

that is created is designed to collect 

food when it enters the stomach, 

which will give patients a feeling of fullness 

after small meals. 

“In essence the company takes the 

good parts of bariatric surgery – stapling 

the stomach so that it is much 

smaller – while eliminating the bad – 

piling patients’ intestines on their 

chests while the doctor re-plumbs their 

guts,” Tom Gibson, Satiety spokesman, 

told Medical Device Daily. The TOGA 

procedure is designed to be less invasive, 

require less recovery time and have 

reduced complications compared to 

existing surgical options, Satiety said. 

Satiety used the TOGA procedure on 

220 patients in a pilot trial which 

showed good weight loss data. The 

company expects to shortly complete 

enrollment in a 303-patient, multi-center, 

randomized and sham-controlled 

pivotal trial being conducted at nine 

centers in the U.S. and one outside the 

country. 

Satiety plans to submit a PMA to the 

FDA in the third or fourth quarter of 

2010. The company needs to show that 

60 percent of the patients had at least 

a 25 percent excess weight loss after 

one year. 

Satiety, founded in 2000 by serial 

inventor and entrepreneur Thomas 

Fogarty, of Menlo Park, Calif.-based 

The Foundry, develops tools for endoscopists 

and gastrointestinal surgeons 

with technology to support the treatment 

of obesity. 

In July 2007, Satiety reported the closing 

of a $30 million Series D financing 

led by new investor Skyline Ventures. 

Other new investors included HLM 

Venture Partners and Pinnacle 

Ventures. Existing investors Venrock, 

Three Arch Partners, Morgenthaler 

Ventures and Thomas Fogarty also participated 

in the financing. John Freund 

of Skyline Ventures joined the company’s 

board of directors and Stephen 

Sullivan of Skyline and Al Wiegman of 

HLM became observers to the board. 

USGI Medical – IOP 

USGI Medical Inc., of San Clemente, 

Calif., is developing the Incisionless 

Operating Platform (IOP) for use in the 

treatment of obesity, as well as natural 

orifice and single-port GI procedures 

such as gall bladder removal and treatments 

for GI cancer, gastrogastric fistulas 

and gastroesophageal reflux disease. 

The company received 510(k) clearance 

in 2007 for devices used in endolumenal 

procedures. They include expandable 

tissue anchors, the g-Prox tissue 

grasper and approximation device, and 

a variety of endosurgical tissue 

graspers. The products have been used 

in more than 250 clinical surgeries in 

the U.S., with no significant adverse 

events. The company believes that its 

tissue anchoring system is more durable 

for treating obesity than traditional stapling 

or suturing. 

The IOP enables surgeons to perform 

revision or primary surgery through the 

patient’s mouth, thereby eliminating 

the need for external incisions in the 

body and reducing post-op complications. 

Operating endolumenally offers 

the promise of faster healing, less scarring 

and less pain, which should lead to 

quicker recovery. 

The company’s initial focus is on 

bariatric surgery but it is moving toward 

more general use in obesity/metabolic 

surgery. The principal challenges for 

incisionless surgery are to create a sensation 

of feeling for the surgeon and to 

attain a durable endolumenal wound 

closure after anatomical reconfigura- 

tion. The GI tract is very resistant to 

reconfiguration. (For more on USGI, see 

the section on revision surgery.) 

Silhouette Medical – nObese 

Prunedale, Calif.-based Silhouette 

Medical Inc. is developing minimally 

invasive technologies for appetite suppression 

and digestion changes as a 

mechanism for inducing weight loss 

and potentially reducing the onset of 

Type II diabetes. 

Its first product, nObese, is a patented, 

non-surgical, non-implantable 45minute 

outpatient procedure weight 

control system. The actual treatment 

time is three to five minutes. A balloon 

with embedded electrodes is introduced 

into the stomach and air-inflated. 

Radiofrequency energy is then 

applied to thermally modify targeted 

sites within the stomach. It is geared for 

individuals who have body mass indexes 

between 25 and 39. 

Certain hormonal receptors are affected, 

which reduce the appetite response 

without interfering with absorption of 

essential nutrients. In addition, the targeted 

areas of the stomach shrink, 

which decreases its elasticity and ability 

to expand. Both processes contribute to 

a feeling of satiety sooner while eating. 

The company has performed 400 procedures 

on three different animals: 

dunnarts, rats and pigs. Compared to 

shams, the animals experienced a 

weight decrease of about 20 percent 

within one month of the operation. 

They continued to eat, but had smaller 

portions. After one year, the pigs 

showed a weight decrease of 40 percent, 

which leveled off at five months. 

Silhouette Medical said it planned to start 

clinical trials in Australia in the second half 

of 2009. The company also plans to study 

onset Type II diabetes to determine its 

relationship to weight loss. International 

commercial launch is planned for the latter 

half of 2010, with U.S. launch slated 

for the latter half of 2011. 


82 

Endosphere 

Endosphere Inc., of Redwood City, 

Calif., is clinically testing an endoscopically 

implanted device that assists 

patients in losing weight and controlling 

Type II diabetes. The device is an 

intestinal/duodenal restrictive implant 

that is about 25 cm long and is placed 

in the duodenum and antrum. The Cshaped, 

self-anchoring implant restricts 

flow through this area, thereby increasing 

contact between the digesting food 

and the receptors of the duodenum. 

This physiological device approach to 

weight loss is believed to create a feeling 

of satiety with a smaller volume of food 

and to help regulate glucose production. 

About 15 hormones are involved in satiation. 

A feasibility study was conducted 

on 11 patients. They felt no sensation of 

the implant and all patients lost weight. 

The company successfully completed an 

initial trial outside the U.S. and is preparing 

for more extensive trials in 

Switzerland. Endosphere expects to gain 

marketing approval outside the U.S. 

within 18 months and FDA approval 

within four years. 

BAROnova – TransPyloric Shuttle 

BAROnova Inc., of Goleta, Calif., is 

developing the non-surgical, non-pharmacologic 

TransPyloric Shuttle (TPS) 

weight-loss technology. BAROnova’s 

weight-loss technology uses a mechanical 

approach that ideally causes the 

patient’s stomach to fill up more quickly 

and to stay full longer, triggering the 

body’s natural intake-reduction 

processes. The TPS is inserted – and 

later removed – entirely through the 

mouth, using simple endoscopic procedures. 

According to the company, the 

TPS is potentially much safer, easier to 

use, and more cost effective than other 

approaches on the market, and it 

requires no surgery. 

Investor Corey Mulloy, of Highland 

Capital, said, “Current obesity intervention 

devices are only approved, 

with certain exceptions, for patients 

with a body mass index (BMI) of 40 or 


higher. The World Health Organization 

classifies as obese any person with a 

BMI of 30 or above. BAROnova’s TPS 

technology is targeted at the extensive, 

unserved population with a BMI 

of 30 and above.” 

According to the Centers for Disease 

Control and Prevention, approximately 

30 percent of the U.S. population is 

obese, with a BMI of 30 or greater. But 

less than approximately 25 percent of 

those obese individuals exceed the BMI 

40 threshold. The rest are below. 

“BAROnova is potentially providing 

new therapy to these millions upon millions 

of individuals,” added Mulloy. 

“This is important technology.” 

BAROnova Gets $7.5 Million 

In October 2008, BAROnova reported 

the closing of its Series B financing of 

$7.5 million, led by a strategic investment 

from Irvine, Calif.-based Allergan 

Inc., a global multi-specialty health 

care company with a leading portfolio 

in obesity intervention devices. Series 

A investors, Arboretum Ventures, 

Highland Capital Partners and ONSET 

Ventures, filled out the round. 

The proceeds will be used to continue 

the clinical development of its TPS 

weight-loss technology, and to fund 

ongoing operations. This brings total 

investment in BAROnova to date to 

$14 million. 

“Clinical obesity and its side effects, such 

as diabetes, are a significant health problem 

in the U.S. and elsewhere and safe 

and effective intervention presents real 

market opportunities,” said Rob Kuhling, 

managing director of ONSET Ventures. 

“BAROnova’s technology speaks directly 

to a segment for whom surgical or medical 

intervention is too risky, too expensive, 

or otherwise contraindicated.” 

ValenTx 

Carpinteria, Calif.-based ValenTx Inc. is 

focused on the development of a lessinvasive, 

implantable medical device to 

address morbid obesity. The company 

aims to emulate the proven mechanisms 

of bariatric surgery using a minimally 

invasive implantable device. 

James Wright, president of ValenTx, 

said in a release that while the company 

still is early in its development, “the 

encouraging results from clinical study 

of our technology have been presented 

at four major scientific meetings.” 

ValenTx Closes on $22M Series B 

Preferred Funding 

In September 2009, ValenTx reported 

the closing of a $22 million Series B preferred 

stock financing. The round was 

led by SV Life Sciences and joined by 

Covidien Ventures, as well as all the 

company’s existing venture capital 

investors: Sapient Capital, EDF 

Ventures, Kaiser Permanente Ventures, 

Affinity Capital Partners and TGap 

Ventures. 

“This financing is an important corporate 

milestone for ValenTx in its development 

of a proprietary less-invasive 

treatment for morbid obesity and the 

diseases, like diabetes, associated with 

morbid obesity,” said Mitchell Dann, 

founder and principal of Sapient 

Capital and chairman of ValenTx’s 

board. “The additional capital 

resources from our new and existing 

partners position the company for clinical 

and regulatory development 

towards commercialization.” 

Other Surgical Platforms 

SafeStitch Medical 

SafeStitch Medical, of Miami, is developing 

endoscopic and minimally invasive 

surgical devices. Its product portfolio 

includes a gastroplasty device for 

endoscopic bariatric surgery and endoscopic 

repair of gastroesophageal reflux 

disorder (GERD), as well as an endoscopic 

device for excision and diagnosis 

of Barrett’s esophagus. 

The noninvasive gastroplasty device can 

treat two separate disorders: GERD and 

morbid obesity, both of which “are par-

ticularly serious health issues in the western 

hemisphere and major contributors 

to the escalating cost of health care in 

the U.S.,” said Charles Filipi, of 

Creighton University School of Medicine. 

He added, “We believe that this device 

will result in much more effective treatments 

for both conditions, fewer complications 

and less patient expense, 

while permitting each procedure to be 

performed on an outpatient basis.” 

Conventional treatments for GERD and 

obesity are performed surgically, requiring 

hospitalization and the potential for 

complications. GERD is the third-mostprevalent 

disease in the U.S., with more 

than 19 million people suffering from it 

weekly and 61 million Americans 

reporting heartburn monthly. 

The device, a flexible tube with a metal 

capsule at the tip, is introduced through 

the mouth and esophagus, suctions two 

sides of the specified juncture in position 

for suturing, removes the mucosal 

lining, then stitches the two sides back 

together. The theory being that by 

suturing mucosa-to-mucosa, a stronger 

bond is formed and the resulting durability 

allows it to last longer, distinguishing 

this procedure from other noninvasive 

methods that have been developed. 

Safestitch Medical has developed the 

device with licensed intellectual property 

from Creighton University. 

TransEnterix – Spider System 

TransEnterix Inc., of Research Triangle 

Park, N.C., has created a single-port, 

multi-channel laparoscopic surgical 

platform called the Spider System. The 

Spider System – which stands for 

Single Port Instrument Delivery 

Extended Reach – allows surgeons to 

perform minimally invasive abdominal 

surgeries entirely through a single port. 

According to the company, it will not 

leave a visible scar. 

TransEnterix plans to launch the Spider 

System in early 2010. It received the 

2009 “Innovation of the Year” award 

from the Society of Laparoendoscopic 

Surgeons. 

“The Spider System is extremely userfriendly. 

Surgeons who are comfortable 

with current laparoscopic techniques will 

adapt easily to our new platform,” said 

Todd M. Pope, TransEnterix president 

and CEO. 

The company was founded in 2006 by 

Synecor LLC, a business accelerator that 

creates proprietary, disruptive technologies 

in the medical device and combination 

drug/device markets. 

TransEnterix Raises $55M in Series 

B Financing 

TransEnterix reported in October 2009 

that it secured $55 million in a second 

round of institutional financing, paving 

the way for the company to manufacture 

and market its laparoscopic surgical 

platform. Aisling Capital led the Series B 

financing, which included Intersouth 

Partners and Quaker BioVentures as 

new investors, as well as current 

investors SV Life Science Advisers, 

Synergy Life Science Partners and Parish 

Capital Advisors. 

EndoVx 

Napa, Calif.-based EndoVx Inc. was 

founded in 2004 and is focused on a 

medical device system for a non-invasive 

obesity treatment. Benefits include 

that the procedure is quick and is done 

on an out-patient basis. Effective longterm 

weight loss was shown in a 

human surgical study. 

Neuromodulation Is an Emerging 

Market 

Electrical stimulation to suppress the 

appetite or create a feeling of satiety is 

achieved by laparoscopically placing 

electrodes in the stomach or on the 

vagus nerve that are attached to a small 

pacemaker-like generator. The gastrointestinal 

tract is not altered, so the 

mechanism is neither restrictive nor 

malabsorptive, but rather interferes 

with hunger signals. 

EnteroMedics – Vbloc 

Brain to stomach, brain to stomach, 

ALERT: food is on the way, start 

expanding. Stomach to brain (as food is 

consumed): not satisfied yet, send more 

food. This is essentially the conversation 

that takes place between a person’s 

brain and stomach, usually from the 

minute the nose senses food. And this 

communication is the reason that 

EnteroMedics Inc. has developed its 

alternative to weight-loss surgery: a 

technology designed to slow down or 

even block the signals from the brain to 

the stomach and back again. 

EnteroMedics, of St. Paul, Minn., makes 

devices using neuroblocking technology 

to treat obesity and other gastrointestinal 

disorders. Its neuroblocking 

technology, Maestro System, also 

known as Vbloc vagal blocking therapy, 

is designed to intermittently block the 

vagus nerves using high-frequency, 

low-energy, electrical impulses. It is 

designed to trick the patient’s digestive 

tract into feeling full after a small meal. 

The Maestro system is its initial product 

for the treatment of obesity. Some have 

anticipated that the system also would 

help to reverse diabetes because the 

vagal nerves affect the release of intestinal 

hormones. 

Vbloc therapy is a high-frequency 

blocking technology, not a stimulation 

therapy as used by other companies in 

the neuromodulation space, Greg Lea, 

the company’s senior vice president and 

CFO, told Medical Device Daily. 

Lea explained that surgeons used to routinely 

cut the vagus nerves near the 

stomach to treat ulcers, a procedure 

known as a vagotomy. When they did 

this they noticed right away that patients 

lost their appetite and started to lose 

weight, Lea said. So, in 2002, based on 

an analysis of the vagus nerve’s control 

of food intake and processing, 

EnteroMedics was founded to develop a 

therapy to treat, primarily, obesity. 

Vbloc therapy is delivered through 


84 

leads implanted laparoscopically in the 

abdomen to intermittently block vagal 

nerve trunks. High-frequency, lowenergy 

electrical impulses are delivered 

by an implantable system to block the 

messages conveyed through the vagal 

nerves. If desired, the Vbloc delivery system 

can be removed, and previous 

studies in animals have indicated that it 

does not damage or permanently affect 

the vagal nerves. 

Like other weight-loss procedures, the 

benefit of losing weight is complemented 

by an improvement in co-morbidities so 

frequently associated with obesity, such 

as Type II diabetes and hypertension. But 

unlike the laparoscopic banding and gastric 

bypass procedures, the improvements 

in co-morbidities do not correspond to 

weight loss, Lea said. He said in many 

patients the minute the Vbloc therapy is 

applied, or soon thereafter, the patient’s 

hypertension improves, as well as the diabetic 

condition. 

President and CEO Mark Knudson said, 

“Obesity is a growing epidemic worldwide 

[and] Vbloc Therapy is a treatment 

innovation that offers individuals the 

promise of significant weight loss without 

having to accept nutritional, lifestyle 

and safety compromises.” 

The company said Vbloc therapy is the 

first to treat obesity using neuroblocking 

technology and represents a less-invasive 

alternative to existing surgical weight loss 

Neuromodulation Products and Companies 


procedures, “which alter digestive system 

anatomy, lifestyle and food choices 

and may present significant risks.” 

As of October 2009, the company had 

$34.8 million in cash on hand with a 

burn rate of roughly $7 million per 

quarter. It filed for an IPO in 2007 and 

raised 40 million through the effort. 

EnteroMedics went public in November 

2007, raising about $40 million. While 

it was a substantial IPO by most medical 

device standards, the amount raised 

was about half what the company had 

hoped for. Difficult market conditions 

and a decrease in investors’ appetite for 

early stage, non-revenue-producing 

companies had a major impact. 

Neuroblock Therapy Works Even at 

Low Signals 

High-frequency, low-energy electrical 

impulses or low intensity signals – 

either way, it appears that the 

EnteroMedics neuroblocking technology 

to treat obesity seems to work. 

Preliminary results, albeit unexpected, 

from the EMPOWER study, were reported 

in November 2009 and revealed that 

the control arm of the study reaped 

almost as much benefit from the therapy 

as the treatment arm. 

The Maestro System was implanted in 

all study participants. It was turned on 

fully in the treatment arm and at a very 

low signal with the control arm so that 

patients and investigators wouldn’t 

know the difference. To everyone’s surprise, 

those very low signals had a significant 

result. 

“The control arm of the trial, which was 

intended to be inactive, apparently provided 

a low intensity blocking signal 

that introduced Vbloc Therapy,” Mark 

Knudson, president and CEO, said during 

a conference call. “The EMPOWER 

study didn’t meet the primary endpoints 

because there was no difference 

at 12 months between treatment and 

control. The level of weight loss in the 

control arm was unusually high.” 

After 12 months, all patients had lost 

an average of 16.6 percent of their 

body mass index (BMI). Those in the 

treatment arm who used the device an 

average of 10.9 hours per day lost 23.1 

percent and a 22.6 percent loss was 

reported in the control arm. 

“This certainly wasn’t anticipated,” 

EnteroMedics’ investor relations representative, 

David Pitts, Argot Partners, 

told Medical Device Daily. 

In early October, Knudson reported the 

preliminary results and noted disappointment. 

(See “EnteroMedics’ 

Maestro Fails to Meet Endpoints in 

Clinical Study,” below.) But after closer 

analysis of the data, the company realized 

that the device seemed to work 

even in the control group. But before 


Metacure Tantalus Electrical stimulation of antrum N/A Diabetes control/ 

weight loss next 

EnteroMedics Vbloc Neuromodulation of vagus nerve 29% EWL Primary weight loss; 

at 1 year will investigate diabetes 

next 

IntrapaceN/A Gastric pacemaker N/A Primary weight loss 

with closed loop 

feedback 

Leptos Biomedical N/A Implantable pulse generator N/A Primary weight loss 

for autonomic nerve system 

NeuroSigma N/A Deep brain stimulation N/A Primary weight loss 

Source: Presentations at ASMBS, Biomedical Business & Technology.

that happened, EnteroMedics reduced 

its workforce and operating costs in 

order to preserve capital and streamline 

its operations following that initial 

report of those top-line results. That 

reduction lowered the number of 

employees by 40 percent, to a total of 

33. It was expected to result in $3.2 

million in reduced operating expenses 

in 2010. Pitts said those employees 

who were laid off will not be invited 

back despite the positive data because 

the company needs the funding to 

push forward. 

Katherine Tweden, EnteroMedics’ VP, 

research and clinical, further explained 

what happened in the study during the 

conference call. “Before we began 

EMPOWER, the existing literature led us 

to believe that signal blocking was 

related directly to the amount of energy 

delivered to the nerve,” she said. 

“We tested a variety of signal intensities. 

Our preclinical work led us to 

believe that low-intensity signals had 

only a brief and low effect. But the 

cumulative effect of the control arm 

signal may have been sufficient.” 

As an added bonus, the study found 

that participants who had been previously 

diagnosed with hypertension 

experienced a decrease in blood pressure. 

A follow-up study is planned to 

further investigate this benefit. 

“The reduction in blood pressure was 

noticeable at one week and sustained 

through 12 months,” Knudson said. 

Pitts said study investigators originally 

had planned to fully engage the device 

in the control group after 12 months. 

Now all patients have been made 

aware of these preliminary results and 

the study will continue for several more 

years with all patients receiving full 

treatment. 

Another study finding was that the 

longer patients had the device turned 

on, the more effective it was. But even 

those who didn’t meet the prescribed 

nine hours of daily device use, averaging 

6.9 hours of daily use, experienced 

a loss of 10.5 percent of their BMI in 

the treatment arm and 8.6 percent in 

the control at 12 months. 

Knudson said the company was taking 

steps to meet with the FDA to determine 

an appropriate regulatory path for 

this treatment with a morbid obesity 

indication. 

EnteroMedics’ Vbloc Fails to Meet 

Endpoints in Clinical Study 

It was shaping up to be a banner year 

for EnteroMedics. Earlier in 2009 the 

company reported a private placement 

accord that would yield it nearly $16 

million. It also touted the start of the 

EMPOWER study, to evaluate the safety 

and effectiveness of the Maestro 

System (also called Vbloc) for the treatment 

of obesity. But in October 2009, 

the company reported disappointing 

preliminary results from the trial and 

said that it did not meet primary and 

secondary efficacy endpoints. 

“Thoroughly we’re disappointed with 

today’s news,” Mark Knudson, president 

and CEO and founder of 

EnteroMedics, said in a conference call 

when the news was announced. “The 

preliminary results indicate that we did 

not meet our efficacy endpoints. Again 

this data is new to us and we’re evaluating 

the next steps for the Maestro 

system.” 

The EMPOWER Study is a randomized, 

double-blind, placebo-controlled pivotal 

study, that took a look at 294 

patients. The trial was fully enrolled at 

15 sites (13 in the U.S. and two in 

Australia). One-third of the 294 

patients in the trial had the device 

implanted but not turned on while two 

thirds had the device turned on. The 

study blind remained in place for 12 

months after activation of therapy in 

the experimental arm. 

Preliminary data from the study demonstrated 

was that there were no adverse 

affects in the trial but rather there wasn’t 

much of a change in weight loss 

between the two groups. The company 

estimates that weight loss was about 7 

percent to 10 percent. 

“Results were largely indistinguishable 

between on and off groups,” Knudson 

said. “Both groups had weight-loss in 

the mid-teens.” 

The Maestro was touted to regulate 

nerves that control digestion and 

appetite. The company had hopes that 

the device could serve as an alternative 

to bariatric surgery. 

The device includes two small electrodes 

that are laparoscopically 

implanted and placed in contact with 

the trunks of the vagus nerve just 

above the junction between the esophagus 

and the stomach, near the 

diaphragm. 

The electrodes receive electrical impulses 

from a neuroregulator implanted 

under the skin in the abdominal region. 

The major components of the Maestro 

system include: a neuroregulator that 

emits electrical pulses through the lead 

system; a lead system that delivers the 

pulses to the vagus nerve; a controller 

that regulates the rate and intensity of 

the pulses; a transmit coil that delivers 

RF energy and therapy control information 

across the skin into the neuroregulator; 

and a clinician programmer. 

As to what the next step is for the 

device, EnteroMedics played it close to 

the vest and said that it was going to 

take a thorough look at the data before 

it made any decisions about the product. 

The device has already gained CE 

mark approval, but Knudson said the 

company is holding off on any marketing 

until it can review the data from 

EMPOWER. “We haven’t made any 

effort to generate sales [in Europe],” 

Knudson said. 

“If it is not a compliance-related issue 

then I don’t believe there is much hope 


86 

for the technology,” William Plovanic, 

an analyst for Canaccord Adams, said 

in a research report. “If it is a compliance-related 

issue then they need to go 

through another pivotal trial, they need 

to recapitalize the company, restart it 

and try again.” 

The company also reported entering 

into a definitive agreement with an 

institutional investor to sell 6,161,068 

of the company’s shares at a price of 80 

cents per share, for gross proceeds of 

nearly $4.9 million, before deducting 

placement agent fees and estimated 

offering expenses. Canaccord Adams 

acted as the sole placement agent for 

the offering. 

The company said that it intended to 

use the net proceeds of the offering to 

fund clinical studies of Vbloc therapy in 

obesity, hypertension and diabetes, as 

well as for general working capital purposes. 

Vbloc Therapy Receives CE-Mark 

In March 2009, EnteroMedics received 

CE-mark approval of Vbloc therapy 

delivered via the Maestro system for the 

treatment of obesity. 

President and CEO Mark Knudson said, 

“CE-mark approval represents a major 

milestone for EnteroMedics and is the 

first step in our global commercialization 

strategy.” 

The approval gives EnteroMedics the 

ability to market the Maestro system to 

countries of the European Economic 

Area. 

EnteroMedics Raises $15.89M in 

Private Placement 

EnteroMedics said in February 2009 

that it agreed to sell 13,110,393 shares 

of its common stock, together with 

warrants to purchase an aggregate of 

6,555,197 shares of common stock, in 

a private placement transaction with 

several accredited investors. 

The shares were sold for $1.15 a share, 


giving the company gross proceeds of 

$15.89 million before offering expenses. 

The warrants, which had an exercise 

price of $1.38 a share, exercisable at 

any time beginning on the date that is 

six months and one day after the closing 

and ending four years after the closing 

of the private placement. Canaccord 

Adams was sole placement agent for 

the offering. 

EnteroMedics said the proceeds from 

the transaction will be used to fund 

clinical studies of Vbloc therapy in 

obesity, hypertension and diabetes, 

submission for regulatory approval of 

the Maestro system in the treatment 

of obesity upon receipt of satisfactory 

results from the EMPOWER pivotal 

trial, as well as for general working 

capital. 

Vbloc Blocks Signals Between Brain 

and Gut for Weight Loss 

At the beginning of 2009, 

EnteroMedics reported interim data 

from the Vbloc-RF2 feasibility study of 

its Vbloc vagal blocking therapy device, 

the Maestro. The study, taking place at 

two sites in Europe and one in Australia 

and including 38 implanted subjects, 

was designed to evaluate the system’s 

safety and efficacy. 

Follow-up data showed excess weight 

loss of 37.6 percent in nine patients at 

18 months of Vbloc therapy, 28.1 percent 

in 17 patients at 12 months of 

therapy and 17.9 percent in 35 patients 

at six months of therapy, according to 

the company. Also, no deaths or unanticipated 

adverse device events were 

reported. 

Mark Knudson, president and CEO of 

the company, said “These results are an 

encouraging sign that significant weight 

loss, occurring over an extended period 

of time, can take place without the serious 

side effects and adverse lifestyle 

impact seen in other obesity procedures. 

The company reported the co-morbidity 

data earlier the same month at the JP 

Morgan conference. And it also reported 

its 18-month follow-up data showing 

that weight loss is “very consistent” 

with what patients experience in banding 

procedures, with a “much better” 

safety profile, said Greg Lea, the company’s 

senior VP and CFO. 

According to the data, 10 patients with 

diabetes showed a statistically significant 

reduction of 1.1 percentage 

points, from 8.2 percent at baseline to 

7.1 percent at four weeks; and 15 

patients with both systolic and diastolic 

hypertension, which was either untreated 

or controlled with drugs, showed 

statistically significant reductions of 13.9 

mm Hg in systolic pressure and 10.7 

mm Hg in diastolic pressure at four 

weeks. The improvements in blood 

pressure are maintained through six 

months, the company noted. 

EnteroMedics’ study outside the U.S. 

started out with 38 patients enrolled, 

but some patients elected to drop out, 

Lea said, because the company had to 

offer a procedure in laparoscopic banding 

or gastric bypass if they didn’t like 

the Vbloc procedure. 

“Many of them used our procedure to 

jump the queue, getting into our study 

and then six months later saying ‘give 

me lap band,’” he said. “So we had 

some fall out, but we still anticipate 

somewhere between 20 to 25 patients 

in the trial.” 

EnteroMedics Gets $20M Loan 

EnteroMedics reported in November 

2008 that it closed a $20 million working 

capital loan, replacing its existing 

debt agreement. Silicon Valley Bank, 

Western Technology Investment and 

Horizon Technology Management provided 

the financing. Proceeds from the 

loan were slated to supplement the 

company’s $28.6 million in cash, cash 

equivalents and short-term investments 

as of Sept. 30, 2008, and were slated 

to be used to repay the existing balance 

of the company’s working capital loan, 

to fund clinical studies and for general

corporate needs. The loan required 

interest-only payments until June 2009, 

followed by principal and interest payments 

amortized over the next 30 

months. 

MetaCure – Tantalus 

In Greek mythology Tantalus was a 

greedy man who disobeyed the orders 

of the gods by offering them a false 

sacrifice: a meal – in the form of his 

own son. As a result of his transgression, 

whenever Tantalus tried to eat any 

food or drink any water, they would 

recede from his grasp. 

Med-tech company MetaCure Inc., of 

Orangeburg, N.Y., is well aware of the 

troubles of Tantalus and is tapping into 

the story with the launch of its new 

gastric stimulator that plays off of the 

myth. The device’s name – Tantalus. But 

instead of a story about increasing the 

appetite, this Tantalus wants to 

decrease it. 

“This is an implantable device under 

the skin, and it detects whenever someone 

takes a meal,” Naji Abumrad, medical 

director of MetaCure told Medical 

Device Daily. “Once a person takes the 

meal, it sends a stimulus to the stomach. 

The contractions are so strong it 

makes the stomach feel full. The hope 

is that it will control glycemic levels in 

the body.” 

The system is based on technology 

called Gastric Contractility Modulation, 

which is designed to sense naturally 

occurring electrical activity of the stomach 

in real time and apply electrical stimulation 

treatment during meal times. 

Tantalus is comprised of a pulse generator, 

which is the size of a nano-iPod or 

a pacemaker, and leads that are 

implanted through a minimally invasive 

laparoscopic procedure that can be performed 

in about an hour, according to 

MetaCure. The leads, through which 

the electric pulses are delivered, are 

implanted in the gastric muscle, and 

the implantable pulse generator is 

implanted in a subcutaneous pocket in 

the belly. The entire device weighs 

about 75 grams. 

It also comes with external control and 

monitoring components for the patient 

and physician. The device data can be 

read non-invasively by the physician for 

further tailoring of the treatment 

parameters to the patient. 

Tantalus is not approved for sales or 

marketing in the U.S., though the company 

previously said it hoped for a U.S. 

commercial launch in 2010. Tantalus 

was given CE mark approval in 2006. 

Tantalus “is available to patients in 

Europe for the indication to treat Type II 

diabetes with obesity. It has been clinically 

evaluated in more than 100 

patients worldwide,” said Irit Yaniv, 

COO of MetaCure, in 2007. “We look 

forward to potentially being able to 

make it accessible in the future to U.S. 

patients as well.” The company was 

founded in 2003 to develop therapies 

to treat diabetes. 

IntraPace – Abiliti 

IntraPace Inc., of Mountain View, Calif., 

is a medical device company focused on 

the treatment of obesity. It is developing 

a novel implantable system called Abiliti, 

which is implanted via standard laparoscopic 

instruments without making any 

changes to the digestive system anatomy 

and also does not place any limitations 

on what a patient can eat and 

drink (such as in gastric bypass or gastric 

banding). In addition, the system is 

designed for easy removal, if needed. 

The laparoscopic surgery to implant the 

device takes about one hour. 

The company says that the Abiliti system 

is designed to be the first “intelligent” 

obesity intervention: After it is 

implanted, it can detect when food or 

drink are consumed. When it detects 

either, the Abiliti system delivers a 

series of low-energy electrical impulses 

to the stomach, which are intended to 

create a feeling of fullness. These elec- 

trical impulses are customized to the 

needs of each particular patient. In 

addition, the Abiliti system collects the 

output of the food detection and activity 

sensors, and the information can be 

downloaded at a physician’s office. 

IntraPace is conducting clinical trials of 

the Abiliti system in Europe. 

IntraPace Brings in $30M in Series D 

In August 2006, IntraPace completed 

a $30 million Series D financing led by 

Vulcan Capital, the investment group 

of Paul G. Allen. IntraPace said it 

planned to use the funds to complete 

product development and worldwide 

clinical studies. 

Eric Bell, Vulcan Capital’s representative, 

said, “As obesity has grown to 

become a worldwide health crisis, 

solutions provided by IntraPace have 

an opportunity to improve the lives of 

millions of patients.” 

In addition to Vulcan Capital, other participants 

include new investor L Capital 

Partners, and existing investors, DFJ 

ePlanet, Oxford Bioscience Partners, 

Toucan Capital, Guidant (now Boston 

Scientific), Johnson & Johnson 

Development Corp., CB Health Ventures, 

Halo Fund II and The Angel’s Forum. 

Chuck Brynelsen, CEO of IntraPace, 

said “As with our Series C financing, 

this funding round was heavily oversubscribed 

by both current and new 

investors. We believe that this is evidence 

of the increasing interest in 

developing solutions for the treatment 

of obesity which has become a major 

health issue in the United States.” 

Leptos Biomedical – IPG 

Leptos Biomedical Inc. is developing a 

neuromodulation therapy for chronic 

obesity. Its treatment is delivered via a 

pacemaker-type device called an 

Implantable Pulse Generator (IPG). It 

involves the electrical activation of a 

specific nerve in the autonomic nervous 

system. 


88 

Leptos therapy is not approved for sale 

in the U.S., and it is limited to investigational 

use only. Preclinical studies 

have been completed, and the company 

has received approval from the FDA 

to conduct a limited feasibility investigation 

under an Investigational Device 

Exemption (IDE). 

The company was founded in 2002. 

Corporate headquarters are in Fridley, 

Minn., and research headquarters are 

in Redwood City, Calif. Investors 

include Thomas, McNerney and 

Partners, Spray Venture Partners, 

Latterell Venture Partners and 

Technology Partners. 

Sentinel Group – Full Sense 

Sentinel Group LLC, of Grand Rapids, 

Mich., is developing the Full Sense 

device, which is placed via endoscopy 

in the esophageal/cardiac region of 

the stomach. It induces satiety by 

influencing the neurohormonal feedback 

mechanism. It augments fullness 

caused by food and simulates fullness 

in the absence of food. The device is 

easily removable via endoscopy. 

“The Full Sense Device essentially tricks 

the brain into thinking that the stomach 

is full when it is not,” said Fred 

Walburn, president of Sentinel Group, 

in a release. “This technology represents 

potentially the greatest step forward 

in the battle against obesity since 

the inception of bariatric surgery.” 

“This device, so far, is showing better 

weight loss than most surgeries 

because it does not depend on food 

intake.” said James Foote, a doctor 

who performed some of the implants. 

“We believe this technology will be 

another great tool in the fight against 

obesity.” 

At the beginning of 2009, Sentinel 

Group announced the first implants of 

the Full Sense device. In February 

2009, the company announced the 

completion of the first clinical study of 

the Full Sense. Devices were implanted 


for six weeks, and the study evaluated 

weight loss, satiety, safety and removability. 

According to the company, 

patients lost significant weight and 

also noted significant satiety. They 

experienced slight to no hunger 

before meals. In addition, Sentinel 

Group reported that the devices were 

safely removed. 

StimPulse 

StimPulse Ltd., of Kiryat Shemona, 

Israel, is developing a sensing-and-stimulating 

implantable device that senses 

food intake into the digestive system 

and applies electrical stimulation to the 

digestive system in order to reduce the 

ability of further intake of food. Animal 

studies are under way, with fully 

implanted and integrated units that are 

wirelessly connected to a base unit to 

acquire signals from the digestive tract 

and to activate stimulation. 

NeuroSigma 

NeuroSigma Inc., of La Cañada, Calif., 

is developing a technology based on 

research that found that there is a 

region in the brain that controls metabolic 

activity, and by introducing an 

electric current, the metabolic rate can 

be regulated. 

It is working on obtaining FDA 

approval for human clinical trials and is 

moving forward with plans for commercialization. 

The technology previously 

was successfully demonstrated 

on small animals. 

NeuroSigma was founded in 2008, 

and licensed a patent application for 

the technology from the University of 

California, Los Angeles. 

Balloons and Space-Filling Surgical 

Products 

Although intragastric balloons are easy 

to place and serve well as both a bridge 

to surgery and for treating mild obesity, 

they may cause nausea and gastroesophageal 

reflux disorder, but with a 

low complication rate and an estimated 

weight loss of 34 percent at six months 

on average. Balloons and other spacefilling 

products such as gels and foams 

that partially fill the stomach often are 

used as a bridge to surgery for those 

patients who have too high of a risk 

profile for bariatric surgery. 

A space-filling device is placed 

through the mouth and left in the 

stomach for three months to six 

months, allowing patients to feel full 

and reduce their caloric intake so that 

they can lose enough weight to be 

surgery candidates. 

This space also may be one of the first 

to go after the cosmetic, or elective, 

market that allows patients who do not 

meet the National Institutes of Health 

criteria of obesity to obtain the procedure 

under a doctor’s care and self-pay. 

Intragastric Balloon Design Issues 

Intragastric balloons for obesity are 

only available outside the U.S. In the 

states, they were withdrawn after 

deaths occurred after accidental balloon 

deflation. Most designs now 

allow for the balloon to pass safely 

through the digestive system in the 

event of accidental deflation. 

Intragastric balloons are efficacious 

but some have been hampered by 

functional issues related to their 

design, such as difficulty changing balloon 

volume once implanted, inability 

to determine the patient’s optimum 

balloon volume, and migration into 

the small intestine leading to bowel 

obstruction and surgery. 

Allergan – Orbera 

Allergan Inc.’s Orbera Intragastric 

Balloon System is the leading product 

in the intragastric balloon system 

arena. It is in clinicals in the U.S., and 

it is a clinically accepted treatment for 

weight loss in South America and 

Europe, and it is being introduced in 

Canada. The balloon itself is silicone. It 

is inserted endoscopically into the 

stomach and filled with saline through 

a self-sealing valve, which gives

patients a feeling of satiety. After a 

maximum of six months, the balloon is 

removed. 

The Orbera is intended for use in conjunction 

with the adoption of lifestyle 

changes. Patients consult with experts 

about diet, nutrition and exercise, so that 

the habits developed with the Orbera 

system will become long-term changes. 

The primary advantage of Irvine, 

Calif.-based Allergan’s Orbera is that it 

does not involve surgery. Inserting the 

balloon takes about 20 minutes to 30 

minutes. Patients must be on a liquid 

diet for one week after the procedure, 

but afterward can eat solid foods. The 

company estimates average weight 

loss of two pounds per week, or 20 to 

40 pounds over the six months the 

device is used. In three published studies, 

patients lost an average of 46 

pounds, 33 pounds and 46 pounds. 

Helioscopie – Heliosphere 

Helioscopie SA, of Vienne, France, has 

the Heliosphere, an intragastric balloon 

for radical non-surgical intervention 

for severe obesity. Its purpose is to 

occupy a space in the stomach to 

quickly create a feeling of satiety. The 

balloon is implanted for six months, 

and the non-surgical endoscopic 

implantation procedure takes about 

an hour. Unlike other balloons, the 

Heliosphere is filled with air, not a liquid. 

According to the company, “The 

side effects described in the scientific 

literature (nausea, vomiting) have 

Space-Filling Products to Treat Obesity 

been reduced by 80 percent in comparison 

with the liquid balloon.” 

But Helioscopie isn’t looking to win 

FDA approval for any of its gastric 

implants – “at least not anytime 

soon,” Chantal Belin, scientific director 

for the company, told Medical 

Device Daily in 2007. “It is very expensive, 

and the U.S. experience with an 

air-inflated gastric balloon was not 

positive back in the 1980s.” The silicon 

construction of Heliosphere has 

proven effective as well as far lighter, 

she said, eliminating the post-operative 

complications of materials used 20 

years ago. 

Helioscopie started in 2000 with gastric 

rings and received CE-marking for the 

gastric balloon technology in 2004. 

Isère magazine in March 2006 reported 

Helioscopie sales at EUR7 million ($10 

million) and 11,000 implants. Heliogast 

is its range of adjustable gastric bands, 

and Heliosite is its range of implantable 

sites. The company reports that its R&D 

investment is 13 percent of its turnover. 

Spatz FGIA – Adjustable Balloon 

System 

Spatz FGIA Inc., of Jericho, N.Y., and 

Ra’anana, Israel, is developing a nonsurgical 

treatment for obesity using an 

intragastric balloon. Its Adjustable 

Balloon System design avoids migration 

to the duodenum and makes it 

easier and safer to use than other balloon 

devices that have been sold outside 

of the U.S. for more than 10 years. 

The company claims that it yields a 15 

kilogram weight loss over a six-month 

period. 

As its name states, the device is 

adjustable, even after implementation 

inside a patient’s stomach. This is 

because studies have shown that after 

a few months of treatment, a patient’s 

body acclimatizes to a balloon, which 

will start to lose its effect. According to 

Spatz, studies have shown that 80 percent 

of weight loss experienced by 

patients with balloons occurs in the first 

three months. With Spatz’s device, doctors 

can add volume to the balloon, in 

order to encourage similar weight loss 

levels after the three-month mark. The 

additional fluid is added by a physician 

using an endoscopic procedure. 

The adjustability has another use as 

well: Patients often report nausea with 

liquid-filled balloons, and sometimes 

opt to forego treatment and have the 

device removed if the side effects 

become too much. With Spatz’s 

device, a physician can decrease the 

volume of the balloon after a few days, 

then increase it again after a patient’s 

body has a chance to acclimate to the 

device. 

A final feature of the device is a safety 

mechanism that will prevent the balloon 

from leaving the stomach in the 

event of accidental deflation. “The 

Spatz System has a patented uncrushable 

catheter ‘tail’ attached to the balloon, 

preventing it from leaving the 

Company Product Method of Treatment Comment 

Allergan BIB Saline filled bubble 2011 market entry estimated 

Fulfullium N/A Multi-compartment balloon Preclinical trials 

Tulip Medical N/A Pill that expands in stomach; creates tension N/A 

on stomach wall and occupies volume 

Heliosphere N/A Intragastric balloon International 

ReShape Medical N/A Multi-compartment device N/A 

Gelesis Synthetic polymer that swells in stomach N/A 

Barosense TERIS Trans-oral endoscopic implant Feasibility study 

Baronova Trans-pyloric shuttle; delays gastric emptying Filing PMA 

Source: Presentations at ASMBS, Biomedical Business & Technology. 


90 

stomach. Should the balloon deflate, it 

will remain harmlessly in the stomach 

until removed via a standard endoscopy 

procedure,” said Evzen Machytka, the 

doctor who performed the first 

implants with the device. 

“Currently, intragastric balloons must 

be removed after six months, due to 

the rising incidence of balloon deflation 

after six months, which in turn increases 

the risk of intestinal obstruction. 

Spatz FGIA will be presenting evidence 

to the European regulatory authorities 

to show how the Spatz Balloon 

System’s special uncrushable ‘tail’ eliminates 

this risk. Until the regulatory 

authorities approve leaving the balloon 

in place for longer periods, patients and 

physicians will be advised to ensure 

removal of the Spatz System after six 

months,” said CEO Jeffrey Brooks in a 

release. 

In October 2009, Spatz reported that 

the first patients had been implanted 

with the device, at the University 

Hospital in Ostrava, Czech Republic. 

ReShape Medical – ReShape 

Balloon 

ReShape Medical Inc., of San 

Clemente, Calif., is developing the 

ReShape intragastric balloon, which is 

designed to occupy space in the stomach 

to create a feeling of satiety. It is 

implanted endoscopically (attached to 

the end of a catheter), then filled with 

saline. Unlike other intragastric balloons, 

which tend to be comprised of 

one round balloon, ReShape’s product 

is composed of two balloons that are 

attached together by a flexible tube. 

Each balloon has independent channels, 

so the other is not impacted in 

the event of deflation or leaks. It is left 

in a patient for six months, and used 

in conjunction with diet and exercise. 

ReShape has obtained CE Mark and ISO 

certification for the product, and clinical 

investigations are under way outside of 

the U.S. Studies are being planned for 

the U.S. as well. 


Fulfillium 

Fulfillium Inc., of San Francisco, has 

filed a patent for a gastric balloon. 

Other Space-Filling Products 

Tulip Medical 

Tulip Medical Ltd., of Tel Aviv, Israel, is 

developing a disposable and biodegradable 

medical device that is swallowed as 

a capsule and creates pressure or tension 

on the gastric wall, which sends 

satiety signals to the brain, thereby 

reducing food consumption. The product 

is based on reports in medical literature 

that the creation of tension in the 

stomach walls is picked up by stress sensors, 

which cause a feeling of satiety. 

The device’s mechanism of action is 

purely mechanical and does not involve 

any chemical activity, Tulip said. 

In September 2008, 7 Health Ventures, 

a professional venture capital fund 

dedicated to investing in health care 

technologies and products, said it had 

joined a deferred closing of Tulip 

Medical’s Series A financing. 

BaroSense – TERIS 

BaroSense Inc., of Redwood City, 

Calif., is a medical device company 

focused on treatments for obesity. It is 

working on the development of a minimally 

invasive treatment for obesity. 

The BaroSense Trans-oral Endoscopic 

Restrictive Implant System (TERIS) is 

being investigated for safety in 

Canada. It uses an endoscopic procedure 

to implant a restrictive reservoir in 

the stomach, in order to create a sense 

of satiety. The study began in June 

2008, and is expected to be complete 

in May 2010. 

In August 2009, BaroSense reported 

that it raised $27 million, of a targeted 

$30 million, in its fourth round of 

financing. Previous investors joining 

the latest round were Delphi Ventures, 

Frazier Healthcare Ventures, Invesco 

Private Capital, RWI Ventures, Synergy 

Life Science Partners and Wharton 

Ventures. They were joined by new 

investor Pappas Ventures. The amount 

brings the total the company has raised 

to $53 million. BaroSense was founded 

in 2001. 

Gelesis 

Gelesis Inc., of Boston, is a private 

developer of treatments for obesity and 

other unmet medical needs. The 

Boston-based company has remained 

under the radar since its founding in 

2006, and Eric Elenko, interim vice 

president of business development, 

declined to comment on its technology 

or pipeline in 2008. 

Yet Gelesis’ patents may provide a clue 

to its obesity approach. The company 

has intellectual property relating to synthetic 

polymers that swell in the stomach 

to create a feeling of “fullness.” 

Another clue might be gleaned from 

that fact that Gelesis was co-founded 

by ExoTech Bio Solutions, an Israeli 

chemistry company that has developed 

a biodegradable, superabsorbent polymer 

called ExoSAP. 

Whatever Gelesis is up to, the company 

has managed to attract an impressive 

roster of scientific advisors. SAB members 

include Elazer Edelman, of Harvard 

University; former FDA executive David 

Feigal; gastric balloon pioneer Allan 

Geliebter; James Hill, of the University 

of Colorado; Lee Kaplan, of 

Massachusetts General Hospital Weight 

Center; and Stephen Woods, of the 

University of Cincinnati’s Obesity 

Research Center. 

Gelesis was co-founded in 2006 by 

PureTech Ventures and ExoTech Bio 

Solutions, with the participation of a 

group of obesity experts and scientists. 

Gelesis CEO, Yishai Zohar, was formerly 

a partner at PureTech Ventures where 

he co-founded Gelesis. 

In February 2008, Gelesis announced that 

is raised $16 million in a Series A financing. 

OrbiMed Advisors led the round, and 

also participating were Queensland 

BioCapital Funds, PureTech Ventures,

Lansing Brown Investments and the 

Cape Family Fund. Elenko said proceeds 

from the Series A financing would be 

used to drive Gelesis’ mysterious product 

“into appropriate clinical trials.” 

Gelesis also was the recipient of a $1 

million grant from the BIRD 

Foundation, established by the U.S. and 

Israeli governments in 1977 to generate 

cooperation between the private 

sectors of the U.S. and Israeli high-tech 

industries. PureTech, along with its partners, 

provided $900,000 in seed funding 


Sleeve Gastrectomy – An Old 

Procedure Revived 

Sleeve gastrectomy is one of the hottest 

topics in bariatric treatment. The procedure 

initially served as a bridge to surgery 

– actually, part 1 of a two-part procedure. 

Sleeve gastrectomy has grown 

in popularity tremendously because it is 

easy to do, can now be performed 

endolumenally, and patients can later 

add another procedure if necessary. 

Sleeve gastrectomy involves the suturing 

the stomach such that only a sleeve 

is left that allows for a limited amount 

of food passage and was once part of a 

procedure that also included a bypass 

component to it. The big benefit of this 

approach is that in addition to the volume 

reduction, the part of the stomach 

left is that which produces ghrelin, a 

hormone that reduces hunger. Many 

bariatric surgeons can perform sleeve 

gastrectomy laparoscopically, but it can 

be technically tedious. 

Super-obese patients often are unable 

to undergo surgery because they 

require dangerously high amounts of 

sedative due to their large size, have 

interrupted breathing patterns, and 

often have chronic obstructive pulmonary 

disease. These factors put them 

at risk for surgery, so it has been felt 

that if they could lose some of their 

excess weight prior to surgery, they 

could become a candidate for surgery 

with less associated risk. By performing 

the simpler sleeve part of the surgery 

first – called “staging” their surgery – 

they may lose enough weight to go 

back for the rest of their surgery. 

Performing just the sleeve procedure 

caused enough weight loss that some 

of them never returned for the rest of 

the surgery, and also resulted in a new 

wave of “sleeve-only” procedures to be 

performed. 

Simpler, easy to perform surgically, and 

now without incisions, the fad has 

caught on, with good weight loss 

results awaiting long-term studies to 

verify its durability. 

Companies that may benefit from this 

new concept are those that have endoscopic 

staplers, among them Ethicon 

Endo-Surgery Inc., of Cincinnati, and 

Covidien, of Mansfield, Mass. 

Power Medical Interventions Inc., of 

Langhorne, Penn., has developed a 

laparoscopic circular stapler that can 

create the defect, or buttonhole, in the 

antrum, making the procedure simpler 

and quicker to perform. In July 2009, 

Power Medical Interventions said that 

the i60 Mid Cut device was used in a 

procedure known as laparoscopic vertical 

gastroplasty. The procedure was 

successful at reducing the size of the 

patient’s stomach, without removing 

the stomach. This minimally invasive 

procedure resulted in the patient losing 

17 pounds in the first week following 

surgery. Enabled by PMI’s computerassisted, 

power-actuated surgical 

instruments and unique Mid Cut 

Reload, the laparoscopic vertical gastroplasties 

are minimally invasive surgical 

procedures designed to create a narrow 

sleeve in the stomach using staples 

without removing the stomach. As a 

result of the operation, a significant 

portion of the stomach is partially 

sealed off but left in place, reducing the 

overall size of the functioning stomach 

and restricting its intake potential. The 

company was acquired by Covidien for 

$65 million in September 2009. 

The simplification of bariatric procedures 

holds a great deal of promise for 

companies active in the space. (See the 

table “Ideal Bariatric Procedure 

Attributes” for some of the key attributes 

that are driving the growing 

acceptance of such procedures.) 

Ideal Bariatric Procedure 

Attributes 

Endolumenal placement (incisionless) 

Outpatient procedure 

Quick reversal of diabetes 

Excess weight loss of at least 60 

percent at one year 

Costs less than $6,000 

Does not permanently alter intestinal 

architecture 

Allows for future procedures if 

necessary 

Reversible/removable/adjustable 


Technology. 

Lifestyle Medicine 

A big opportunity in obesity may lie in 

a consumer market sector often 

referred to as “lifestyle medicine.” Not 

to be overlooked is the fact that 

Americans spend $30 billion annually 

on weight loss programs, pills and 

nutritional supplements in order to 

manage their weight. 

With this as a backdrop, one wonders 

how much an overweight person 

would spend to lose weight if he or she 

could get a minimally invasive, 

reversible or temporary procedure done 

in an office or outpatient setting? It is 

not inconceivable that with some of the 

newer devices that avoid major surgery 

and can be performed in an office or 

outpatient setting, patients could selfpay 

and have a weight loss procedure 

by choice before they become obese. 

The lifestyle medicine sector is driven by 

patient demand more than medical 

necessity, and is predicted to be one of 

the fastest-growing areas of health care 

investment, primarily due to the large 

group of baby boomers who have discretionary 

income. And these boomers 


92 

could expand this already huge market to 

include the overweight and not just the 

obese. 

In just a few years, it may be possible 

for a moderately overweight mother to 

elect to have an intragastric balloon 

placed in her stomach six months 

before her daughter’s wedding, as 

insurance that she looks her best – and 

thinnest – on that most important day. 

New Markets Opening for Existing 

Products 

Other “new” markets created by 

bariatric surgeons for existing products 

include using stents to prop open strictures 

or repair leaks following bariatric 

surgery. Roger de la Torre, of the 

University of Missouri, in Columbia, 

presented his findings using stents to 

repair leaks, strictures and fistulas that 

developed after bariatric surgery. He 

tried both nitinol and polyester stents 

and had the best success with multiple 

nitinol stents – usually two long ones – 

placed overlapping each other. The 

biggest issue he had initially was that 

40 percent of them migrated, but he 

found that by using longer nitinol 

stents that overlapped and allowed tissue 

in-growth to anchor them, he 

achieved a 92 percent success rate. 

“Up to 16 percent of bariatric surgery 

patients will suffer from post-op nausea 

and vomiting caused by stromal stenosis,” 

said Daniel Jones, of Boston-based 

Beth Israel Deaconess Medical Center. 

“Balloon dilatation is a highly effective 

way to treat patients with this problem.” 

Another 16 percent of bariatric surgery 

recipients will develop anastomotic ulcers 

– the most common cause of post-op 

hemorrhage. There are a number of existing 

surgical tools to address this problem, 

from delivering thermal energy to applying 

clips, to injecting fibrin glue, or using 

a combination of these therapies. 

Clumped together, these mini-markets 

for new uses of existing medical 

devices can amount to a substantial 

new area of growth. 

Diabetes Control Is Another New 

Market 

There is a strong correlation between 

obesity and diabetes. There are about 

19 million Type II diabetics in the U.S., 

of whom 80 percent are obese. 

Although there is a genetic factor 

involved in the development of Type II 

diabetes, the disease typically is instigated 

by obesity, a lack of exercise, 

poor diet and a sedentary lifestyle. 

Type II diabetes is a metabolic disease 

primarily characterized by relative 

insulin deficiency and hyperglycemia. It 

is often managed by exercise and diet 

modification. Some 90 percent to 95 

percent of all North American cases of 

diabetes are Type II, and about 20 percent 

of the population over the age of 

Endoluminal Products for Weight Loss and Diabetes Control 


65 has Type II diabetes. The fraction of 

Type II diabetics in other parts of the 

world varies substantially, almost certainly 

for environmental and lifestyle 

reasons, though these are not known in 

detail. Diabetes affects more 150 million 

people worldwide, and this number 

is expected to double by 2025. 

Some companies are developing 

implants that are delivered endoluminally 

and are left in place for six months 

or longer, then retrieved on an outpatient 

basis using conscious sedation. 

One company, Lexington, Mass.-based 

GI Dynamics Inc., has everything to gain 

from the movement to diabetes resolution. 

It has developed an endoscopically 

placed Teflon liner placed just beyond 

the pyloris. This device, called the 

EndoBarrier, creates a mechanical 

bypass of the duodenum and proximal 

jejunum. It allows food to pass through 

the device, and allows bile and pancreatic 

enzymes to travel outside the liner, 

allowing bile and gut hormones to travel 

around the liner without touching 

the food until later in the gut, thus 

mimicking a gastric bypass. 

EnteroMedics Inc., of St. Paul, Minn., 

has developed the Vbloc vagal blocking 

system and a neuromodulation system 

that is comprised of a pacemaker-type 

device and leads that are implanted 

laparoscopically around the vagal nerve. 

The company’s intermittent vagal block- 


Valentx N/A Artificial stoma with sleeve that 40% at 12 Primary weight loss/ 

bypasses the stomach and duodenum weeks diabetes control 

GI Dynamics Endobarrier Gastrointestinal impermeable 22% at 1 year Primary weight loss/ 

liner that bypasses duodenum (first generation) diabetes control 

Endosphere N/A C-shaped nitinol implant 12% EWL* at Primary weight loss/ 

placed in duodenum 1 month diabetes control 

Gastrx N/A Mimics gastrectomy and vagotomy N/A Primary weight loss/ 

diabetes control 

Silhouette N/A RF ablation in the antrum N/A Primary weight loss 

Medical to impair gastric emptying 

Notes: *EWL = excess weight loss, the benchmark used to determine effectiveness of the device/surgery. 

Source: Presentations at ASMBS, Biomedical Business & Technology.

Companies with Interventional Therapies for 

Obesity and Diabetes in Development 

Neuromodulation 

Enteromedics (St. Paul, Minnesota) 

Leptos Biomedical (San Francisco/Minneapolis) 

Endolumenal Implants That May 

Mimic Surgical Procedure 

GI Dynamics (Lexington, Massachusetts) 

Valentx (Wilson, Wyoming) 

Endosphere (Silicon Valley, California) 

Endolumenal Surgical Platform 

TransEnterix (Durham, North Carolina) 

USGI Medical (San Clemente, California) 

Ethicon Endo-Surgery (Cinncinnati) 

Covidien (Mansfield, Massachusetts) 

C.R. Bard (Murray Hill, New Jersey) 

Satiety (Palo Alto, California) 

Endogastric Solutions (Redmond, Washington) 

EndoVx (Napa, California) 

BaroNova (Goleta, California) 

Barosense (Menlo Park, California) 

Safestitch Medical (Miami) 

Endolumenally Placed Balloons 

Fulfillium (Napa, California) 

Allergan (Santa Barbara, California) 


ing system involves a less-invasive 

option to gastric bypass and lap banding 

and provides a means of tricking the 

alimentary tract into feeling full after a 

small meal. Should the patient’s digestive 

system outsmart the sensory 

impulses delivered by Vbloc, the therapy 

can be non-invasively adjusted to a new 

waveform to which the digestive tract 

may respond more optimally. 

ValenTx Inc., of Carpinteria, Calif., 

incorporates a restrictive stoma along 

with a malabsorptive sleeve, while 

Endosphere Inc., of Redwood City, 

Calif., has created an implant that 

delays throughput through the duodenum 

with the intention of both weight 

loss and diabetes remission. 

Some key opinion leaders have speculated 

that with a better understanding 

of diabetes and how these implants 

function, it may be feasible in the 

future to implant these devices in normal 

weight diabetics to provide remission 

of their diabetes without dependence 

on insulin. 

In a presentation at the American Society 

of Metabolic and Bariatric Surgeons in 

June 2009, it was found that the longer 

and more overweight a diabetic patient 

was before having bariatric surgery, the 

less able they were to resolve their diabetes 

following surgery, suggesting that 

the mechanism responsible for controlling 

diabetes had just been “burned 

out.” It also showed that with weight 

regain after surgery there was an accompanying 

increase in diabetes, further 

demonstrating the interdependence of 

the two diseases and encouraging obese 

diabetics to seek surgery sooner and to 

keep the weight off. 

Body Composition Analyzers 

Determining the amount of weight – 

and the amount of weight to lose – is a 

critical step in efforts to lose weight. At 

the annual Obesity Society meeting, the 

number of exhibitors offering equipment 

for analyzing body composition 

has increased over the years with the 

notable addition of the leading companies 

that market bone densitometers 

for monitoring osteoporosis, namely, 

Hologic Inc. and GE Healthcare, of 

Waukesha, Wis. Body composition 

scans with dual-energy X-ray absorptiometry 

(DEXA) provided precise data 

on bone and tissue composition, 

including bone mineral density, lean tissue 

mass and fat tissue mass. These 

measurements help physicians monitor 

the effects of therapy, diet and exercise. 

Bruker Optics 

Bruker Optics Inc., of Billerica, Mass., a 

leading manufacturer of spectrometers, 

has the TD-NMR spectrometers for 

determining body composition, such as 

lean/fat ratios on animals. Its Minispec 

contrast agent analyzer is used to study 

the effect of MRI contrast agents on the 

NMR relaxation of water or fat in vivo 

and in vitro. 

Cosmed 

Cosmed, of Rome and Chicago, has 

Fitmate equipment, which measures 

oxygen consumption in real time for 

determining resting energy expenditure 

for use in weight management, fitness 

assessment and exercise prescription. 

Echo Medical Systems 

Echo Medical Systems LLC, of Houston, 

markets the EchoMRI whole body composition 

analyzer for humans and animals 

that measures body fat, total body 

water and bone density by utilizing MRI 

and CT-based techniques. 

Hologic 

Hologic Inc., of Bedford, Mass., has the 

Discovery series of bone densitometers. 

Its OnePass makes bone density measurements 

of the hip and spine in 10 

seconds. The performance of this test is 

supported by the FRAX study which 

assessed fracture probability in men 


94 

and women in the UK and was published 

in Osteoporosis International in 

February 2008. 

ImpediMed 

ImpediMed Ltd., of Queensland, 

Australia, and Rochester, N.Y., has the 

Imp SFB7, a tetra polar bioimpedance 

spectroscopy device that scans 256 frequencies 

from 4 kHz to 1000 kHz to 

determine the total body water and 

extracellular fluid from impedance 

data. Fat-free mass and fat mass are 

calculated on the device. Similar data 

are obtained from its Imp DF50 instrument, 

which uses a single frequency at 

50 kHz to analyze body composition. 

Jawon Medical 

The Plusavis 333 analyzer from Koreabased 

Jawon Medical Co. Ltd. measures 

body fat composition using conductivity 

to calculate a biological factor 

representing different types of body tissue 

that is based on five factors: 

weight, height, impedance, age and 

gender. 

Korr Medical Technologies 

Korr Medical Technologies Inc., of Salt 

Lake City, has the ReeVue indirect 

calorimeter that measures the body’s 

consumption of oxygen from a 10minute 

breath test which is used to 

measure a patient’s resting energy 

expenditure. This technique is used for 

nutritional assessment and medical 

nutrition therapy. The company was 

acquired by Daelim Solar Co. Ltd. in a 

reverse merger in late 2008. 

Life Measurement 

Life Measurement Inc., of Concord, 

Calif., manufactures body composition 

assessment devices using air displacement 

plethysmography. Its BOD POD 

body composition tracking system measures 

percent fat and lean body mass in 

adults and children. The PEA POD makes 

the same assessment in infants. 

Tanita 

Tanita Corp. of America, of Arlington 

Heights, Ill., is a leading provider of pre- 


cision scales. Its WB-3000 digital beam 

scale features an automatic body mass 

index calculation. Tanita uses bioelectrical 

impedance analysis, which entails 

passing an electrical signal through the 

body, which is carried by water and fluids. 

The impedance information is used 

to estimate the amount of lean and fat 

tissue within the body. 

Tanita’s MC-189 is a body composition 

analyzer that uses four frequencies to 

generate a total body analysis which 

includes body fat, muscle mass and 

total body water along with detailed 

information on intracellular and extracellular 

water essential for fluid status 

and illness assessment. 

Bodystat 

Bodystat Ltd., of the Isle of Man, British 

Isles, markets bioelectrical impedance 

analysis equipment for measuring body 

fat, lean muscle, water content and 

body mass index. Its single- and dualmultifrequency 

devices are used to 

determine intracellular and extracellular 

fluid levels. 

Metabolic and Other Testing 

Equipment 

ActiGraph 

ActiGraph, of Pensacola, Fla., markets 

the Actiwatch, a small electronic device 

for 24-hour activity monitoring, used for 

diagnosing sleep disorders, often an 

obesity-related problem. It collects the 

user’s physical activity, limb movements 

or sleep levels. Its rechargeable lithium 

battery provides power for 14 days. 

Actiware-PLM is used for assessing the 

magnitude and periodicity of limb movements 

during sleep. The ActiWeb software 

offers analytical processing options 

including cardiovascular, limb and 

extremity, and sleep reports. The device 

can be used in weight loss/management 

programs to accurately determine caloric 

expenditure versus caloric intake. 

Cosmed 

Cosmed Slr, of Rome, Italy, is a marketer 

of cardiopulmonary diagnostic 

equipment. It has Quark RMR equipment, 

a metabolic cart for clinical nutrition, 

including indirect calorimetry (continuous 

VO2 and VCO2) and metabolism 

substrates (RQ, FAT, CHO and 

PRO). Its Fitmate desktop metabolic system 

is used to accurately measure resting 

energy expenditure. 

Korr Medical Technologies 

Korr Medical Technologies Inc., of Salt 

Lake City, markets the CardioCoach 

VO2 metabolic analyzer. Its ReeVue 

indirect calorimeter measures in a 10 

minute breath test the body’s consumption 

of oxygen, which is used calculate 

a patient’s resting energy expenditure 

(REE) and for nutritional assessment. 

Research indicates that measuring REE 

pre-operatively can be an indicator of 

the success of bariatric surgery. 

Microlife USA 

Microlife USA Inc., of Dunedin, Fla., 

markets the MedGem metabolism 

measurement handheld device that 

measures oxygen consumption to 

determine an individual’s resting metabolic 

rate. 

Mini Mitter 

Mini Mitter, of Bend, Ore., acquired by 

Respironics, of Murrysville, Penn., in 

August 2005, markets the Actical, a 

small, omni-directional accelerometer 

that accurately measures the level of 

the subject’s physical activity and step 

count. Actiheart is a wireless heart rate, 

physical activity and caloric expenditure 

recording system. The company says it 

is the only heart-rate recorder with an 

integrated accelerometer that can calculate 

energy expenditure for ambulatory 

activities. 

Sable Systems 

Sable Systems International Inc., of Las 

Vegas, has the Superior Metabolic 

Intelligence instrumentation and software 

for providing precise metabolic measurement 

for preclinical or in vivo researchers. 

It is used to measure O2, CO2 and water 

vapor, as well as for activity monitoring 

and temperature telemetry.

Seahorse Bioscience 

Seahorse Bioscience Inc., of North 

Billerica, Mass., has the XF24 extracellular 

flux analyzer for determining energy 

expenditure, fatty acid oxidation and 

cell signaling in mammalian cells. The 

instrument works with standard 

microplates and allows reuse of the 

cells for other assays. 

Zen-Bio 

Zen-Bio Inc., of Research Triangle Park, 

N.C., is a provider of primary cell cultures 

and reagents for the study of 

human metabolic disease. 

Behavior Modification for Weight 

Control 

BodyMedia – SenseWear 

BodyMedia Inc., of Pittsburgh, is distributing 

to clinicians its SenseWear WMS, 

a web-based weight management 

solution that focuses on behavior therapy. 

It consists of an armband for the 

automated tracking of activity and 

sleep, and is designed to improve 

weight loss outcomes by increasing 

patient adherence to prescriptions and 

promote lifestyle changes. It enables 

health practitioners and their patients 

to continuously monitor daily behaviors 

such as calories burned, nutrition and 

sleep. 

Study results for SenseWear showed 

that the device can improve treatment 

outcomes when physicians incorporate 

it into weight loss intervention with 

their patients. The results, published in 

the April 2007 issue of Obesity, provide 

data supporting the company’s claim 

that the information gleaned from the 

SenseWear monitor, when used to 

report patients’ metabolic activity, can 

“contribute to behavioral change and 

improve health.” 

“We found that right now, it really does 

help when these individuals download 

[the collected information] at their doctor’s 

offices, and give them more information 

about what they’re doing – such 

as their changes in behavior,” Donna 

Wolf, clinical research manager for 

BodyMedia, told Medical Device Daily. 

Physicians then can “really coach them, 

because we’ve found that the coaching 

aspect really does help the individual.” 

The SenseWear system consists of an 

armband monitor, which weighs less 

than 3 ounces, that records levels of 

activity through several sensor systems, 

including skin temperature, galvanic 

skin response, heat flux and 2-axis 

accelerometer. The company also provides 

software that can be used at 

home to download information from 

the device. Alternatively, the patient 

can take the system to a physician’s 

office and download it there, which is 

where the coaching component enters. 

For the patients, the software translates 

the information into charts and graphs 

to more easily provide a translation of 

the numbers generated by the device. 

The study results examined the effects 

of the SenseWear Body Monitoring 

System on 57 patients enrolled in a 12week 

behavioral weight loss intervention 

program. According to the company, 

the results showed that weight loss 

was greater – about 5 pounds greater, 

Wolf said – among the patients who 

used SenseWear continuously during 

the program. 

Wolf said that often people don’t realize 

how many calories they’re burning, 

or not burning, which allows weight to 

creep up slowly and largely unnoticed. 

The SenseWear system is designed not 

only for those wanting to lose that 

extra 10 to 15 pounds, but also for 

those for whom weight control is critical 

to disease control and prevention – 

such as patients with obesity, cardiovascular 

disease and diabetes. 

The device is Class II exempt, meaning 

it does not require 510(k) clearance. 

Currently, the SenseWear system must 

be purchased through the company, 

which has its own sales and marketing 

team, or through their physicians as an 

out-of-pocket expense. 

GE Healthcare Lunar 

GE Healthcare Lunar, of Madison, Wis., 

is taking a slightly different approach in 

combating obesity – by clearly identifying 

the fat tissue that causes obesity. 

And the $17 billion unit of Fairfield, 

Conn.-based General Electric is starting 

in a unique place – with the bones. 

The Dual Energy X-ray (DXA) is a device 

the company says scans bone mineral 

density in patients, as well as provides 

information to enable licensed medical 

practitioners to simultaneously assess 

body composition and ascertain fat distribution 

in adults. 

The DXA “gives you so much more of 

an accurate reading than what you see 

on the bathroom scale,” Jeff Franz, GE’s 

Global Product manager told Medical 

Device Daily. “The DXA measures the 

fat content in relation to bone mass.” 

The device, which produces an image 

in seven to eight minutes, has been 

used on some fitness reality television 

shows such as ABC’s The Biggest Loser, 

and some football teams including the 

Green Bay Packers also have reported 

using it. 

DXA works by measuring the regional 

and whole body bone mineral density, 

lean and fat tissue mass and calculating 

derivative values that can be displayed 

in user-defined statistical formats and 

trends with color. The device, in conjunction 

with Lunar iDXA software, also 

gives physicians solid data for body 

composition measurements and high 

percentage color fat mapping. GE said 

that patients can easily follow the 

report, which is divided into three compartments: 

lean mass, total body tissue 

percent fat and bone density. 

The derivative values calculated with 

the Lunar Body Composition Software 

include bone mineral content area, soft 

tissue mass, regional soft tissue mass, 

total soft tissue mass, fat free mass, 

regional/total soft tissue mass ratio, 

android percent fat, Gynoid percent fat, 


96 

Android/Gynoid ration (A/G ratio) and 

body mass index. 

But one of the biggest selling points for 

the FDA-cleared device is its ability to 

give an accurate pediatric bone mineral 

density assessment for children, according 

to the company. The DXA systems 

allow physicians to measure a child’s 

bone density, fat and lean tissue mass 

composition, by factoring in and trending 

changes in the child’s skeletal makeup. 

“It’s problematic to measure 

changes in a child’s skeleton because 

their anatomy is changing over time,” 

Franz said. “It’s much easier with adults 

because their skeletons typically don’t 

change unless there’s some sort of 

extraneous circumstance. But the DXA 

will give physicians a reference point 

when screening children. It will measure 

how tall they are compared to their 

peers and it will give information so 

physicians can come to adequate conclusions.” 

Some of those conclusions 

could point out structural deformities in 

the skeleton which could point out 

potential diseases of the bone. 

The company isn’t touting DXA as a 

magic bullet to totally eradicate obesity, 

however. In fact Franz said if anything it 

gives patients the ability to see how to 

safely lose weight and that the actual 

weight loss will have to come from 

lifestyle changes. “Unfortunately the 

only real thing you can do to change 

your body mass is to exercise and to 

diet,” he said. 

Lunar was formed in 1980 and was 

funded through a special grant from 

NASA that studied the affects of bone 

mass with zero gravity. The company 

was purchased by GE in 2000. 

Aipermon 

In the fight against obesity, Munichbased 

Aipermon GmbH & Co. KG 

believes it is not the mass you are carrying 

around that is important, but how 

much you move it that counts. The 

company has some simple tools for 

monitoring patient activity as part of a 


personal health program to reduce 

weight by tracking motion. 

The AiperSunny 333, sold for $85, is 

the low end, yet leading edge, for a 

line of motion detectors that use an 

extremely simple user interface to signal 

whether an individual has been sufficiently 

active during the day to meet 

goals for weight reduction. The interface 

is the classic Happy Face, displayed 

as a smiling sun icon. If the sun 

is less-than-happy, the user needs to 

walk faster or climb some stairs to 

record a higher level of activity and 

score a radiating sun icon. The oneounce 

unit the size of a credit card clips 

onto the user’s belt at the center of 

gravity and measures motion every 90 

seconds, with a 3-D acceleration sensor 

keeping a record in the onboard 

memory chip. Data can be stored for 

up to 21 days and transferred at any 

time to a computer loaded with software 

for a deeper analysis and for setting 

fitness levels for the untrained 

user, the moderately fit individual and 

the “sporty” person. 

Moving up in sophistication is the 

AiperSunny 444 that includes a calorie 

counter. The high end of the line is the 

AiperMotion, selling for $428, which 

features more advanced 3-D sensors 

and a USB interface for downloading 

data. To give an idea of the sophistication 

of the AiperMotion, head of business 

development for Aipermon, 

Christian Hirschbeck, said he wore the 

detector during a recent ski trip to 

Austria and once back at the home 

office after downloading his data was 

able to recreate images of the somersaults 

he performed on the slopes. User 

data for advanced detectors can be 

transferred wirelessly through the 

Aipermon Homebox to an Internet 

server over conventional telephone 

lines. 

iWhisper 

iWhisper Inc., of Menlo Park, Calif., has 

a lightweight and wearable personal 

weight loss device of the same name 

that monitors acoustic signals generated 

by users related to eating and drinking 

and, using a proprietary algorithm, 

processes them to determine how 

much and how fast users eat. It whispers 

short, spoken and real-time feedback 

to help users change their eating 

habits and is based on clinically validated 

behavior modification principles of 

portion and satiation control. 

The device connects via the Internet to 

the iWhisper Network, which tracks 

progress and enables its users to automatically 

communicate with their clinician 

or a real-world virtual coach in 

order to provide the social context 

needed for increased compliance and 

efficacy. iWhisper has been developed 

to the point of a wearable prototype 

that it is capable of detecting eating 

behavior and providing feedback in the 

lab. It can record data and provide realvoice 

feedback in the field. 

MEND Central 

MEND Central Ltd., of London, has a 

program for achieving a measurable 

and sustainable reduction in child overweight 

and obesity levels. It is a government- 

and industry-sponsored free evidence-based 

and family oriented intervention 

program. It combines games 

that stimulate active enjoyment with 

learning about healthy eating and 

behavior modification techniques to 

boost self-confidence. MEND (Mind, 

Exercise, Nutrition . . . Do it!) operates 

in England, Denmark and Australia. It is 

seeking sponsors to fund its expansion 

into the U.S. 

Assisting Weight-Loss Efforts 

A variety of systems focus on providing 

aids to weight-loss efforts. 

Aestis 

Aestis, of Boulder, Colo., has patents 

on the use of controlled hypoxia for the 

treatment and prevention of obesity. It 

is known that hypoxia causes mountain 

climbers to experience weight loss. The 

reduced amount of inspired oxygen 

induces physiological changes equiva-

lent to those seen at high altitudes. 

Aestis is seeking to use this method for 

treating obesity by having the person 

sleep in a tent with low oxygen concentration. 

A small feasibility study on its 

Thin Air system was conducted at 

Maastricht University in the Netherlands, 

which showed weight loss of about one 

pound per week with no significant side 

effects. Currently, hypoxia therapy is 

used by athletes for their training. 

Movea 

The technology behind the popular Wii 

from Nintendo is “pretty lightweight 

technology,” according to Marc Attia, 

who directs sales for Grenoble, Francebased 

Movea SA. He suggests there is a 

lot more science, and especially clinically 

useful information, that can be 

extracted from monitoring the activities 

of patients. Movea holds an interest in 

the Wii game as it acquired the developer 

of the motion sensing technology 

that licensed the patents to Nintendo, 

Saratoga, Calif.-based Gyration. 

Yet Movea is ready to play at a new level 

with the SmartMotion Development Kit 

it launched during the world’s largest 

medical trade fair, Medica 2009 in 

November. SmartMotion is a software 

development platform that allows original 

equipment manufacturers (OEMs) to 

integrate motion sensors into diverse 

products for obesity prevention, for 

functional physical therapy, such as the 

measurement and diagnosis of joints, for 

biofeedback, such as estimated calorie 

burn, for sleep analysis, and for monitoring 

the elderly patient in home care or 

long-term care facilities. 

The SmartMotion software engine 

includes sensor fusion algorithms that 

are “sensor agnostic,” according to 

Attia, capable of precisely measuring 

and recording body movements regardless 

of the tiny wireless, and therefore 

wearable, micro-electro mechanical system 

(MEMS) being employed. 

Movea offers an advanced sensor for 

integration, the MotionPod, a wrist- 

watch-sized device to rapidly integrate 

and customize the use of wireless multisensors 

in its applications. It also 

includes a companion application, the 

MotionDevTool that has an intuitive 

graphical user interface for real-time 

visualization and integration. 

“We have more serious science behind 

motion detectors than scoring points 

on a game,” said Attia, calling up a 

graphical interface for clinicians that 

extracts specific activities, such as sitting, 

walking or lying down, and critically, 

an activity called “transfer” when 

a patient changes position, which is the 

most intensive with the use of muscles 

and the resulting burning of calories. 

Human body orientation and precisely 

quantified motion measures combined 

with other body-worn sensors for 

blood glucose, oximetry or heart rate, 

can remotely provide a wealth of data 

about a patient’s condition. 

Earlier in 2009, Movea signed an agreement 

for joint development of monitors 

for sports activity with Oxylane, of 

Villeneuve d’Ascq, France, the EUR4 billion 

(US$6 billion) retail distributor that 

designs in-house its own products. 

Movea marketing director David Macias 

said, “We are going to being doing a 

lot with Oxylane in developing motion 

sports and motion life style with greater 

sophistication and accuracy than consumers 

are familiar with though computer 

game programs.” 

“Motion sensing is a crowded space on 

the high end where the product configurations 

are not user-friendly and not 

mobile,” said Macias. “We enter this 

space with a core capability for world 

class research with Movea and the heritage 

of Gyration for developing lowcost 

consumer products,” he said. 

Founded in March 2007 by a team of 

researchers from the CEA, Movea 

raised EUR7 million in its first financing 

round, enabling the acquisition of 

Gyration. Attia said the company will 

seek a second financing round in 2010 

and also will launch a third generation 

version of its MotionPod. 

Novartis Medical Nutrition 

Novartis Medical Nutrition, of 

Minneapolis, promotes its Optifast diet 

as a useful regimen six to eight weeks 

prior to bariatric surgery as a way of 

shrinking the size of the liver and reducing 

blood sugar levels, as well as its 

Resource and Optisource post-bariatric 

surgery products which are specially 

formulated to meet the patient’s needs 

for proteins, vitamins and minerals. Its 

Boost Diabetic diet (40 percent carbohydrates, 

20 percent to 30 percent protein, 

and 30 percent to 35 percent fat) 

is based on new nutrition guidelines 

from the Joslin Clinic in Boston. 

Phoenix Care 

Phoenix Care, a unit of Estenda 

Solutions, of Conshohocken, Penn., 

provides patient and practice management 

services for the bariatric surgery 

marketplace. It recently launched software 

that can be used to improve 

patient outcomes and clinic efficiency 

by combining optimized access to traditional 

health care metrics. It is designed 

to assess and manage the long-term 

behavioral changes required of bariatric 

patients. 

Suzuken 

Suzuken Co., a Japanese manufacturer 

of pharmaceuticals and medical equipment, 

has the Kenz Lifecorder EX monitor 

for clinical and health/fitness professionals 

to monitor the physical activity 

of their patients. It analyzes exercise 

intensity, time, frequency, energy expenditure 

and steps. The company also markets 

under its Kenz brand a line of electrocardiographs 

and Holter monitors. 

Obesity-Related Diagnostics 

Interleukin Genetics 

In June 2009, Waltham, Mass.-based 

Interleukin Genetics Inc. launched a 

new all-encompassing brand for its per- 


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sonal genetic tests under the trademark 

Inherent Health. Under this umbrella 

resides a weight reduction program 

based on a first-of-its-kind test, the 

Weight Management Genetic Test. The 

test identifies genetically based tendencies 

for the body’s metabolic behavior 

that affect weight gain. 

Louis Perusse, of Laval University in 

Quebec, author of the Obesity Gene 

Map, collaborated with Interleukin 

Genetics to develop the test. The genes 

used in the test were selected based on 

clinical data that support their impact 

on body weight. 

The test’s unique combination of genetic 

markers addresses variations in 

metabolism, carbohydrate absorption, 

fat absorption and storage. Perusse 

said, “This test and the related tools will 

be an important aid for individuals to 

help them manage their weight based 

on genetic influences.” 

Many other genetics and nutrition 

experts collaborated, providing topnotch 

advice. The company says its 

affordable, simple swab test will be 

ordered online from the Inherent Health 

site. Once tested, an individual will 


receive an interpretation of results and 

personalized guidance on key action 

items that can help control body weight. 

That advice covers diet, nutrition and 

exercise options that can have the highest 

impact on that particular subject’s 

weight loss. It also should allow the 

person to keep weight off. It allows 

access to additional web-based weight 

management tools, for the input of 

ongoing nutritional, exercise and 

weight data. 

Commenting on the company’s 

approach, Interleukin CEO Lewis 

Bender said, “The interest level, usefulness 

and science of genetic testing have 

grown significantly over the past few 

years.” He added, “We believe that evidence 

found through multiple studies 

linking specific genetic variants to 

potential negative health outcomes, 

when coupled with well-packaged and 

meaningful guidance, can provide consumers 

with valuable insights to 

improve their present wellness and 

future health outcomes.” 

Quantomix 

Quantomix, of Nes-Ziona, Israel, has 

developed a method for high-resolu- 

tion imaging and quantitative measurement 

of lipid accumulation in cells and 

tissues using its proprietary Wetsem 

technology. It provides images and data 

that reveal tissue morphology and visualization 

of precise intracellular structure. 

At the cellular level, obesity is 

caused by an increase in the number 

and size of adipocytes (fat cells), and 

the measurement of fat cell size can 

therefore serve as an accurate indicator 

of the effectiveness of intervention. 

Other Obesity Diagnostics 

Diagnostic Systems Laboratories Inc., 

of Webster, Texas, acquired by 

Fullerton, Calif.-based Beckman 

Coulter in October 2005; Alpco 

Diagnostics, of Salem, N.H.; and 

Phoenix Pharmaceuticals Inc., of 

Belmont, Calif., provide a wide range 

of kits for homeostasis and metabolism 

immunoassays. These include 

obesity-related peptides such as ghrelin, 

PYY, adiponectin and leptin. 

Phoenix also has a test kit for nesfatin-1, 

a newly discovered obesity 

peptide that is a satiety molecule 

found in the hypothalamus, and 

obestatin, a new peptide encoded by 

the ghrelin gene that opposes ghrelin 

effects on food intake.

Fat-Fighting Enzyme Can 

Play Havoc with Cancer Cells 

An enzyme that normally helps break down stored fats goes 

into overdrive in some cancer cells, making them more 

malignant, according to findings by a team at the Scripps 

Research Institute. The aggressiveness-promoting enzyme, 

called monoacylglycerol lipase (MAGL), may provide a new 

target for treating more malignant forms of cancers or for 

preventing cancer progression. The findings also suggested 

an explanation for the reported link between obesity and 

cancer by showing that releasing stored fats in cancer cells 

can push them toward more aggressive behaviors. 

Scientists compared changes in the functional state of 

enzymes in nonaggressive cancer cells to that of aggressive 

ones. Among the many enzymes detected, MAGL – a type 

of enzyme, called a lipase, that breaks down stored fats, or 

lipids – stood out as being highly elevated in aggressive cancers. 

Through a series of experiments where researchers 

either inhibited or stimulated MAGL’s activity, they were 

able to establish that the enzyme is capable of converting 

cancer cells from less to more malignant forms. 

They also discovered that when the MAGL becomes more 

active in cancer cells it breaks down stored fats to produce 

large amounts of free fatty acids – the building blocks of 

cell membranes and of fatty molecules that serve as signals 

to and from cells. Those free fatty acids then go on to produce 

other smaller molecules known to promote cancer 

growth and progression. The finding that MAGL regulates 

the production of free fatty acids in aggressive cancer cells 

provides a possible explanation for the reported link 

between obesity and cancer. 

Many more experiments are needed to evaluate whether 

blocking MAGL’s activity might serve to curb cancer’s progression 

in people, which could offer a new type of cancer 

therapy. Because the enzyme is not needed for cell survival 

– rather for progression to more aggressive behaviors – it 

may offer some advantages over existing therapies. 

For Bone, Appetite Regulators, 

It’s Location, Location, Location 

While bone remodeling is certainly recognized as being tied 

to large medical problems – women older than 50 are predicted 

to have a 50 percent risk of developing a fracture 

over their lifetime, a statistic that has made anti-osteoporosis 

drugs among the best-selling drugs on the market – 

research into bone remodeling is not considered “glamorous,” 

Gerard Karsenty told the audience at a talk at the 

National Institutes of Health at the end of 2009. 

SCIENCE NEWS 

Science Highlights: 

Recent Research Breakthroughs in the Battle of the Bulge 

The reason for bone remodeling’s dowdy reputation, 

Karsenty said, is that in the modern world, when bone 

remodeling goes wrong, it is no longer deadly. “It doesn’t 

kill anymore,” he said. And “by extension if the disease is 

not interesting, than function is not interesting.” But 

Karsenty disagrees. “Bone is the only organ that contains a 

cell type” – namely, the osteoclast – “whose only function 

is to destroy the host tissue,” he pointed out. And a function 

that has been preserved over 3 million years “is not just 

to send older and wealthier ladies to the endocrinologist at 

the end of the 20th century and the beginning of this one.” 

Karsenty, who is professor and chairman of the department 

of genetics and development at Columbia University, 

described his own team’s journey to understand bone 

remodeling – which, he said, has “profound implications for 

the treatment of disorders as diverse as diabetes and osteoporosis, 

traditionally regarded to be distinct and unrelated.” 

In a nutshell, Karsenty’s hypothesis can be summed up as 

the idea that “bone mass, appetite and reproduction are 

controlled by the same hormones.” That idea, Karsenty 

said, came from clinical observations that osteoporosis follows 

gonadal failure, and obesity protects from osteoporosis, 

as well as the realization that evolutionarily, being able 

to repair injured bone was much more critical than it is 

today. “If you cannot repair a fracture, you lose mobility,” 

he said, and for most of human history, repairing fractures 

has been a do-it-yourself activity. “Bone remodeling is your 

very own orthopedic surgeon,” he said. 

Karsenty, whose team has been looking at bone remodeling 

for more than a decade, began with studying leptin, which 

appears during evolution with the osteoclast, and is a wellknown 

player in appetite regulation. Leptin also influences 

bone mass, but research into how it does so, Karsenty said, 

soon uncovered a seeming paradox: Destroying the part of 

the brain with most leptin receptors leads to increased bone 

mass and obesity. But knocking out those same leptin 

receptors genetically had no effect on bone mass – or, for 

that matter, body mass index. 

Lesion experiments have their critics as being a brute-force 

method, akin to smashing a radio to see how it works, and 

so the easiest interpretation of such conflicting results is to 

assume that the more modern and more specific technique 

must provide the true answer. But Karsenty’s conclusion 

was a different one: that leptin does play a role, but primarily, 

by acting elsewhere. 

Karsenty focused his suspicion on serotonin, because sero- 


100 

tonin reuptake inhibitors, or SSRIs, are a class of antidepressants 

that both lower bone mass and decrease appetite. 

Through a series of experiments, his team has worked out 

how serotonin signals to increase bone mass and decrease 

appetite in the brain – actions that are inhibited by leptin. 

Moreover, serotonin that is synthesized in the gut – which 

happens to be most of it – has the opposite effect on bone 

mass: Via the wnt co-receptor lrp5, it inhibits osteoblasts, 

bone-making cells that work in tandem with osteoclasts to 

regulate overall bone mass. “I don’t know of any other molecule 

that takes the opposite influence on the same physiological 

function depending on its site of synthesis,” 

Karsenty said. 

Karsenty said that in the aggregate, his team’s work might 

lead to new approaches to treating osteoporosis. Going 

after lrp5 might allow tweaking bone buildup by 

osteoblasts rather than bone destruction by osteoclasts, an 

approach which he termed a “holy grail” of osteoporosis 

drug development. 

As a separate point, he added, the work supports his skepticism 

of using invertebrate models to study vertebrate biology. 

Unlike developmental biology, which has been driven by 

discoveries in simple-to-work-with invertebrates, “when 

one speaks of vertebrate physiology, you cannot really rely 

on fly or C. elegans. . . . If you study physiology in vertebrates, 

it has to be done with a vertebrate animal model. 

This notion that there is a conservation of genes and of 

gene function is so dominant that we think that because it 

is true in developmental biology, it will be true in physiology. 

And it is not,” Karsenty added. 

Insulin, Body Temp Related 

A team led by scientists at the Scripps Research Institute in 

late 2009 discovered a direct link between insulin and core 

body temperature, the first time the hormone has been 

connected to the fundamental process of temperature regulation. 

The scientists found that when insulin was injected 

directly into a specific area of the brain in rodents, core 

body temperature rose, metabolism increased and brown 

adipose (fat) tissue was activated to release heat. The 

research team also found that those effects were dosedependent 

– up to a point. The researchers said the work 

highlighted the possibility that differences in core temperature 

may play a role in obesity and may represent a therapeutic 

area in future drug design. The research was published 

in the online issue of the journal Diabetes. 

Study Shows Fat Around 

Heart Decreases Heart Functions 

Researchers from Boston University School of Medicine 

(BUSM) showed that fat collection in different body loca- 


tions, such as around the heart and the aorta and within 

the liver, are associated with certain decreased heart functions. 

The study, which appeared online in Obesity in 

November 2009, also found that measuring a person’s body 

mass index (BMI) does not reliably predict the amount of 

undesired fat in and around these vital organs. BUSM 

researchers compared fat volumes in obese persons (BMI 

over 30), all of whom had high blood pressure and/or diabetes, 

and lean healthy persons (average BMI of 22). All 

subjects underwent MRI and proton MR spectroscopy to 

quantify pericardial and peri-aortic lipid volumes, cardiac 

function, aortic compliance and intra-hepatic lipid content. 

Fasting plasma lipoproteins, glucose, insulin and free fatty 

acids were also measured among the subjects. The 

researchers found fat collections in anatomically separate 

locations, such as within the liver and around the heart, to 

be associated to cardiovascular function – including a 

decrease in cardiac pumping function – as fat around the 

heart increased. However, they also found that the amount 

of fat around the heart and aorta was not predicted by the 

BMI of the individual in this population. “Our study found 

that fat collection around the heart, the aorta and within 

the liver is clearly associated with decreased heart functions 

and that an MRI can quickly and noninvasively measure fat 

volume in these areas. Our study also found that looking at 

BMI of the individual does not reliably predict the amount 

of undesired fat in and around organs,” said James 

Hamilton, senior author and project leader, and a professor 

of biophysics, physiology and biomedical engineering at 

BUSM. 

Starting Weight a Factor in Bypass Surgery 

According to a study of clinical characteristics of teens who 

underwent laparoscopic Roux-en-Y gastric bypass surgery 

from 2002 until 2007, doctors may have a much narrower 

window of opportunity to reverse morbid obesity in teens 

than previously thought. The study, conducted at Cincinnati 

Children’s Hospital Medical Center, appeared in the October 

2009 online edition of The Journal of Pediatrics. 

The results of the study showed that one year after the 

study, BMI in the overall group of teens pre-surgery 

decreased by 37 percent, however because of their starting 

weights, the teens were still considered to be morbidly 

obese. This means that doctors can predict what a patient’s 

weight will be one-year post weight loss surgery. 

New Obesity Target Involves 

Use of a ‘Molecular Shunt’ 

With the U.S. population now obese, overweight and normal 

weight at nearly equal proportions, obesity is a large 

market in more ways than one. A paper in the June 2009 

issue of Cell Metabolism reported on a potential new target 

that could be harnessed to treat obesity.

In the experiments reported in Cell Metabolism, researchers 

from the University of California, Los Angeles, used what 

they termed a “molecular shunt” to protect mice from the 

consequences of a high-fat diet. The authors inserted the 

genes for two metabolic enzymes – isocitrate lyase and 

malate synthase – into cultured liver cells as well as mice. 

These enzymes are normally part of the metabolic system of 

plants and bacteria, but not mammals. Expression of the 

enzymes increased the metabolism of fatty acids, which are 

used as energy sources by liver and skeletal muscles, in liver 

cells. Mice engineered to have the glycoxylase shunt were 

resistant to diet-induced obesity. 

The authors wrote in their paper that the resistance “was 

accompanied by a decrease in total fat mass, circulating leptin 

levels, plasma triglyceride concentration, and a signaling 

metabolite in liver, malonyl-CoA, that inhibits fatty acid 

degradation.” Malonyl-CoA is part of the pathway that 

determines whether dietary fat will be burned or stored. 

Normally, Malonyl-CoA is high after eating a meal, blocking 

fatty acid metabolism. By lowering Malonyl-CoA levels, the 

shunt enables the body to keep metabolizing fatty acids in 

situations where they normally would be converted into 

body fat. 

While it is unlikely that the concept of gene therapy will 

carry over for the treatment of obesity, the findings suggest 

that malonyl-CoA may be a good target for therapies aimed 

at ramping up fat breakdown. More generally, the authors 

say that “given the success in engineering synthetic phenotypes 

in microbes and mammalian cells, constructing nonnative 

pathways in mammals has become increasingly 

attractive for understanding and identifying potential targets 

for treating metabolic disorders.” 

Studies: Links Among Obesity, 

Inflammation, Insulin Resistance 

Exactly what constitutes an optimal weight – and the consequences 

of not being at it – remains a subject of debate, 

and studies have come to differing conclusions about the 

relationship between weight, health and life expectancy. 

But obesity is linked to several health problems that collectively 

are known as metabolic syndrome – a group of symptoms 

that predispose to coronary artery disease, Type II diabetes 

and stroke. 

The two most important risk factors in metabolic syndrome 

are obesity – especially central obesity, or extra weight 

around the middle – and insulin resistance. Recent studies 

have pointed to a causal link between those two symptoms 

via chronic inflammation of fat tissue. 

Two new studies from overlapping groups of Japanese 

researchers have reported new insights into the connection 

among obesity, inflammation and insulin resistance. One 

implicated angiopoietin-like protein 2, while the other 

assigned such a role to tumor suppressor p53. 

The first study, which appeared in the Sept 2, 2009, issue of 

Cell Metabolism, tested the role of angiopoietin-like proteins 

in promoting fat tissue inflammation. Angiopoietin-like proteins 

are a family that shares sequence similarities with the 

angiopoietins, which promote the formation of blood vessels, 

but do not bind to the same receptors. Angiopoietinlike 

proteins also share structural similarities with fibrinogen 

– which is how they caught the attention of the study’s 

authors in the first place: Fibrinogen often accumulates at 

sites of inflammation, prompting them to look for fat tissuederived 

proteins with sequence homology to fibrinogens. 

In a combination of cell culture and animal studies, the 

authors showed that angiopoietin-like protein 2 is secreted 

by fat tissue, that its levels are higher in mice fed a high-fat 

diet and that its secretion is increased by conditions that put 

stress on the endoplasmic reticulum. 

In mice, chronically activating the protein’s production led to 

skin inflammation and insulin resistance, while knocking it 

out reduced both body fat content and symptoms of inflammation 

in the fat tissue that was left, regardless of whether 

they were fed standard lab chow or a high-fat diet. 

Interestingly, the authors noted, that reduction in weight and 

body fat content occurred despite the fact that the knockouts 

did not eat any less, on the average, than their wild-type littermates. 

The knockouts also showed “slightly, but significant, 

better glucose tolerance and insulin sensitivity.” 

In humans, the levels of circulating angiopoietin-like protein 

2 correlated with body mass index and insulin resistance; 

for instance, levels of the protein fell in a group of obese 

diabetic men after they were treated with Actos (pioglitazone, 

Takeda Pharmaceutical Co. Ltd.). 

The authors concluded that their findings indicated that 

angiopoietin-like protein 2 is an “important part of the 

mechanism underlying adipose tissue inflammation that is 

involved in the pathogenesis of systemic insulin resistance 

related to obesity” and that this understanding . . . led to 

“new treatment strategies for obesity and related insulin 

resistance.” If angiopoietin-like protein 2 is not strongly 

associated with any particular function, then p53 certainly 

is: It is a critical tumor suppressor. But p53 also has been 

shown to be related to insulin sensitivity – and both to cellular 

aging – in fruit flies. And a study published in the Aug. 

30, 2009, online edition of Nature Medicine extended the 

findings into vertebrates, specifically showing that p53’s 

effects on insulin resistance come via its influences on 

inflammatory processes. 


102 

Like the authors of the Cell Metabolism paper, those 

authors fed their mice a high-fat diet to increase inflammatory 

processes. When they blocked p53 expression, they 

improved insulin sensitivity and decreased inflammatory 

symptoms in their animals. 

Conversely, a group of transgenic animals overexpressing 

p53 showed “higher expression of pro-inflammatory 

cytokines and a macrophage marker,” which was associated 

with the impairment of insulin sensitivity and glucose 

tolerance, and provided “further evidence for a major role 

for adipose tissue p53 in insulin resistance.” 

New Factor for Converting Cells 

to ‘Good’ Brown Fat Identified 

Obesity is the excess accumulation of fat cells. But just like 

there is good and bad cholesterol – and for that matter, 

good and bad dietary fat – there is bad and what could be 

good body fat. And in the July 29, 2009, advance online 

edition of Nature, scientists showed how to turn one into 

the other. The authors said in their paper that their findings 

“may provide opportunities for the development of new 

therapeutics for obesity and Type II diabetes.” 

The exact relationship of obesity to health, and even what 

a healthy weight is, remains controversial. But the massive 

increase in average mass over the past few decades clearly 

has led to follow-on problems such as diabetes and heart 

disease, straining not just garments, but also national 

health systems, at the seams. Even globally, the number of 

overweight people now rivals those that are malnourished. 

Somewhat counterintuitively, there is a fat type that could 

help in the fight against obesity: brown fat, which uses the 

energy stored in fat to produce heat. Brown fat cells have a 

high number of mitochondria, which metabolize the actual 

fat they contact. The iron in those mitochondria gives brown 

fat its color, and its name. Brown fat is very important for 

animals that hibernate, preventing them from freezing to 

death. But it also exists in human newborns, and imaging 

studies have shown that adults, too, have brown fat 

deposits. Previous studies had identified one transcription 

factor, the zinc finger nuclease PRDM16, that initiates the 

process by which immature muscle cells either mature or 

become brown fat cells. But the earlier studies also suggested 

that PRDM16 acted in tandem with a second protein. 

In their paper, the authors – from Harvard Medical School 

and Beth Israel Deaconess Medical Center in Boston – 

described searching for that second protein through a combination 

of mutating PRDM16 and proteomic analysis. That 

process allowed them to identify eight candidate transcription 

factors; one of them, the protein C/EBP-beta, was jointly 

enriched with PRDM16 in brown fat cells. The team next 


showed that co-expressing both factors was enough to tilt 

the developmental program toward brown fat development, 

not just in immature muscle cells, but also in fibroblasts 

of both mice and humans, and in adult skin cells. 

When such engineered brown adipose tissue or eBAT cells 

were transplanted into mice, they went about their business 

of metabolizing fat at a high rate. In fact, eBATs had a higher 

basal metabolic rate than real brown fat cells, though the 

engineered variant was unresponsive to external stimulation 

that increases the rate of real brown fat cells, causing 

the authors to note that “some other aspect . . . unknown 

at this point, seems to be limiting in the engineered brown 

fat cells.” 

Senior author Bruce Spiegelman, professor of cell biology at 

Harvard Medical School’s Dana-Farber Cancer Institute, said 

in the press release that the results “give a lot more credence” 

to the idea that brown fat could be harnessed as a 

potential means of treating those with obesity and diabetes. 

That possibly could be achieved via autologous transplantation 

with cells engineered to express PRDM16 and C/EBPbeta. 

But a less invasive method would be to find activators 

of the two transcription factors. “If we can find a hormone 

that does that,” Spiegelman said, “it’s reasonable to think 

that it might provide a direct anti-obesity treatment.” 

Targets Are Identified for Battle of the Bulge 

Scientists are once again coming to the rescue in the battle 

of the bulge, reporting several potential new targets for 

anti-obesity drugs. In the December 2008 issue of Cell 

Metabolism, researchers from Louisiana State University, the 

University of Alabama, Cambridge University and 

Biomeasure Inc. reported on a new fat-signaling mechanism: 

the peptide adropin, secreted by the liver in response 

to high-fat foods and down-regulated in obese animals. 

The researchers found adropin through a screening for 

changes in liver gene expression in response to a high-fat 

diet. Adropin, which is encoded by the gene Enho, or energy 

homeostasis, also is expressed in the central nervous system 

(CNS). Senior author Andrew Butler, associate professor at 

Louisiana State University’s Pennington Biomedical Research 

Center, told BioWorld via email that “the potential role of 

adropin in the brain will be of interest to many. . . . Studies 

examining the regulation of the gene in the CNS, how 

administering the peptide centrally affects metabolism, and 

also deactivating the gene specifically in the CNS, are studies 

that are on our wish list.” But for the time being, he added, 

his team is “focused on the liver because this was the first tissue 

where we identified the gene and how it is regulated.” 

Using both cell culture and in vivo experiments, the 

researchers found that adropin regulates genes that are 

involved in both carbohydrate and fat metabolism. It is

acutely up-regulated by a high-fat diet, but down-regulated 

in animals that are genetically predisposed to obesity, or 

become obese due to a high-fat diet. Transgenic animals 

that expressed high levels of adropin show less fat in their 

livers and become more responsive to insulin. The mice also 

ultimately eat less and lose weight compared to controls, 

but their improved metabolism is independent of such 

weight loss. When the authors administered a synthetic version 

of the peptide to animals, improved metabolism preceded 

weight loss. The authors concluded that adropin 

“provides a promising new lead for developing therapies 

against the metabolic disorders associated with obesity.” 

Adropin’s expression appears to be specifically regulated by 

the fat content of the diet, making it the second recently 

discovered signaling mechanism that responds specifically 

to the fat content of a meal. In the Nov 26, 2008, issue of 

Cell, scientists from Yale University and the University of 

Cincinnati showed evidence that one type of lipid that is 

produced in the gut – N-acylphosphatidylethanolamines, or 

NAPEs – rises after eating fatty foods. NAPEs then enter the 

bloodstream and go to the brain, where they concentrate in 

the hypothalamus, a midbrain region that controls many 

aspects of feeding. 

Like adropin, NAPE levels appear to decrease in response to 

chronic overeating. And like synthetic adropin, synthetic 

versions of NAPE also appear to be a potential path toward 

controlling both food intake and metabolism. When rats 

were administered NAPE directly to their brains for roughly 

a month, they ate less and lost weight. The authors concluded 

that treatment with synthetic NAPE “is capable of 

generating a state of negative energy balance over multiple 

days and merits longer-term studies in rodents and nonhuman 

primates to examine its potential for treatment and 

prevention of diet-induced obesity.” 

In Feeding, Metabolism, It’s All About Location 

Several papers published near the end of 2008 explored 

new pathways and potential drug targets involved in 

metabolism. But at the same time, known players also are 

being explored in greater detail: New work on both the 

neurotransmitter serotonin and the jun kinase pathway clarify 

just how and where they contribute to metabolism and 

its discontents. A paper in the Dec. 5, 2008, issue of Science 

delved into detail about how activation of the jun kinase 

pathway in fat tissues can cause insulin resistance in the 

liver. The jun kinase, or JNK, pathway is activated by cellular 

stress, making it familiar to cancer researchers. But it also 

appears to be involved in regulating metabolism. Its activity 

is increased in insulin resistance and diabetes, and its inhibition 

can improve glucose metabolism. 

But which cell type is critical has been an open question. 

Specifically, some studies suggest that it is JNK in fat tissue 

that is to blame, while others suggest that JNK expression 

in macrophages, by affecting the expression of cytokines, 

ultimately results in insulin resistance. In their Science paper, 

the authors, from the University of Massachusetts Medical 

School and Pennsylvania State University College of 

Medicine (the latter fittingly located in Hershey, Pa., home 

of the chocolate empire) created mice that lacked the JNK 

gene specifically in fat tissue, and found that in contrast to 

their wild-type cousins, such animals did not develop insulin 

resistance in response to a high-fat diet. In contrast, animals 

lacking JNK1 specifically in myeloid cells or blood stem cells 

still developed insulin resistance when they binged on fat. 

The authors also looked for changes downstream of the 

JNK pathway, and found that activation of the JNK pathway 

in fat cells appears to increase the secretion of the proinflammatory 

cytokine interleukin-6. Interleukin-6 activates 

the expression of another protein, SOCS3, in the liver. 

SOCS3 inhibits insulin signaling in wild-type animals, but 

not in fat cell JNK1 knockouts where a high-fat diet 

increased levels of SOCS3 in the liver. Interleukin-6 is the 

target of Actemra (tocilizumab), a monoclonal antibody 

from Genentech Inc. that received FDA approved in January 

2010 as a treatment for rheumatoid arthritis. An accompanying 

editorial in Science suggested that based on the new 

data, tocilizumab “might also prove effective for the treatment 

or prevention of Type II diabetes.” Actemra’s approval 

had been delayed since fall 2008 after the FDA asked for a 

risk evaluation and mitigation strategy (REMS) plan and 

more data. It was the first interleukin-6 receptor-inhibiting 

monoclonal antibody ever approved in the U.S. for arthritis. 

Like the JNK pathway, serotonin’s involvement in eating is 

not news. In fact, fenfluramine – the “fen” part of the withdrawn 

diet drug Fen-phen – activates serotonin receptors. 

Unfortunately, fenfluramine affects serotonin receptors on 

the heart as well as in the brain, and cardiac side effects led 

to the drug’s withdrawal. Now, a paper in the Nov. 26, 

2008, issue of Neuron shows the importance of serotonin 

receptors in one specific neural type in the brain’s feeding 

region: Pro-opiomelanocortin or POMC-expressing neurons 

in the hypothalamus. 

The authors first created knockout mice lacking the 2C subtype 

of serotonin receptor – the subtype that is important 

for regulating eating – and then specifically re-expressed 

the 2C receptors in the POMC neurons. The global knockouts 

exhibited excessive eating, hyperactivity and obesity, 

and showed reduced responses to fenfluramine. But mice 

with serotonin 2C receptors only in POMC neurons were 

like wild-type animals in feeding behavior, weight and their 

response to fenfluramine, suggesting that these neurons 

are critical targets for feeding behavior. However, the 


104 

authors caution that “our findings do not demonstrate that 

POMC neurons are the only site where [serotonin 2C receptors] 

regulate energy balance, as our results do not exclude 

the possibility that other redundant neuronal populations . . . 

may also be sufficient to mediate similar effects.” But, they 

add, their model will allow them – or other scientists – to 

address the question of whether the POMC neurons are 

unique in their importance, or one of many redundant feeding 

circuits. 

Hypothalamic Overeating Gene Pegged 

The chemistry of obesity is of great interest given the impact 

of the condition on the nation’s health care tab, and an 

announcement at the NIH website points the finger at neurochemistry 

as a contributing factor. According to the 

August 2008 announcement, the chemical compound in 

question, known as brain derived neurotrophic factor 

(BDNF), is also involved in the transition of recall from shortterm 

to long-term memory, and animal studies have hinted 

at a role for BDNF in appetite regulation. In 2002, 

researchers in France observed that immobilization stress in 

rodents increased BDNF expression in the region of the rat 

hypothalamus that also governs the release of other hormones, 

including the stress-response steroid cortisol. 

The current study, however, is not of healthy patients, but 

those who suffer from WAGR syndrome, which is described 

as a rare genetic syndrome giving children a predisposition 

to development Wilms kidney tumors, an absence of the 

colored part of the eye known as aniridia, abnormalities of 

the genitourinary tract, and mental retardation. A team led 

by Joan Han, of the National Institute of Child Health and 

Human Development at NIH analyzed the chromosomes of 

33 patients with WAGR and determined that 19 “had deletions 

of all or a major proportion of one copy of the gene 

for BDNF.” Each of the 19 was obese by the age of 10 and 

demonstrated a propensity to overeat, and “all of the 19 

had blood levels of BDNF that were roughly 50 percent 

lower than those of patients who had two working copies 

of the BDNF gene.” The statement also noted that the 

remaining patients with “two working copies of the BDNF 

gene were no more likely to develop childhood onset obesity 

than the general population, and did not report unusually 

high levels of overeating.” 

Whether the results of this study, which appeared in the 

Aug. 28, 2008, edition of The New England Journal of 

Medicine, can be extrapolated to anyone with a less damaged 

set of genes is difficult to say, but the authors note 

that the subjects in the study “have large, heterozygous . . . 

deletions” of the genes in question, and a further analysis 

of other gene samples hints that a more restricted set of 

damages to those genes might have a similar effect on 

appetite control. NICHD Director Duane Alexander 


described the study as “a promising new lead in the search 

for biological pathways that contribute to obesity,” expressing 

the hope that it will “eventually lead to the development 

of new drugs to regulate appetite in people who have 

not had success with other treatments.” 

Systems Biology Approach 

Finds Novel Obesity Genes 

In two papers published online in Nature in March 2008, 

researchers from deCode Genetics Inc., Merck subsidiary 

Rosetta Inpharmatics Inc. and several collaborators have 

used a systems biology approach to identify several new 

candidate genes that affect obesity. The findings also supported 

the notion that metabolic syndrome is a true condition 

rather than a constellation of symptoms that occur 

independently but frequently enough to give the appearance 

of being associated. 

Genomewide association studies, Eric Schadt told 

BioWorld, “try to find the signpost in the genome” by 

searching for changes in DNA sequences that correlate with 

changed disease risk. But “the change in DNA doesn’t 

cause disease directly,” Schadt pointed out. And it is rare 

that a change in only one gene can be tied neatly, switchlike, 

to a change in disease susceptibility. 

Schadt, a researcher with Rosetta, likened the genetic 

underpinnings of disease to “lots of light switches scattered 

all over the genome. And they don’t operate independently 

of each other.” 

In their papers, Schadt and his team first analyzed nearly 

24,000 transcripts in large samples of two types of tissues: 

blood samples from about 1,000 individuals and fat samples 

from almost 700. The scientists also measured several 

obesity-related characteristics including body mass index 

and percentage of body fat for the tissue donors. The 

researchers first correlated the expression of each of the 

transcripts with obesity-related physical traits, and found 

that the expression of 60 percent to 70 percent of genes in 

the fat cells correlated with physical obesity markers. In the 

blood cells, less than 10 percent of transcript levels were 

associated with obesity. They next used bioinformatics 

methods to determine a core network, and several subnetworks, 

of genes that are “enriched for genes involved in the 

inflammatory and immune response and . . . causally associated 

to obesity-related traits,” the authors wrote. Their 

method yielded three specific genes – lipoprotein lipase, 

lactamase b and protein phosphatase 1-like or Ppm1l – that 

the scientists validated in animal studies as previously 

unknown obesity genes. 

The findings also suggested that metabolic syndrome – 

which is a major risk factor for heart disease that consists of

the simultaneous occurrence of high blood pressure, obesity, 

impaired glucose tolerance, low levels of HDL cholesterol 

and high levels of triglycerides – is indeed a cohesive 

group of symptoms. There has been some discussion of 

whether metabolic syndrome is nothing more than frequent 

conditions occurring together independently of one 

another. But Schadt said that “both papers definitely suggest 

that the subnetwork is one of the networks that tie 

all of these different diseases together.” He specifically 

pointed to Ppm1l as a gene that “affects all of the core 

traits together,” having an effect on obesity, diabetes and 

hypertension. The three genes, of course, could make 

potential therapeutic targets. But Schadt also pointed to 

the big picture when asked about the therapeutic relevance 

of the findings. At their most basic level, the findings 

underscored that “diseases are much more complex 

than we thought,” he said, involving an interconnected 

web of many genes. But the systems biology approach to 

dissecting those interconnections, he said, are “absolutely 

driving a lot of work at the early stage about what nodes 

in the network to target.” 

Peripheral Endocannabinoids 

Linked to Fatty Liver Disease 

The best known endocannabinoid receptors are in the 

brain, and responsible for the psychoactive effects of marijuana. 

But in the March 2008 issue of Cell Metabolism, 

researchers from the National Institute on Alcohol Abuse 

and Alcoholism report that endocannabinoid receptors also 

stimulate the main type of liver cells, the hepatocytes, to 

store excess fat. Such storage can lead to alcoholic fatty 

liver or steatosis, a disease in itself and the possible precursor 

to even more serious liver conditions such as cirrhosis. 

Furthermore, the endocannabinoids that activate them are 

secreted by another liver cell type: the hepatic stellate cell, 

a support cell known to date for its role in structural support 

and secreting collagen, which is important in injury 

repair but also can lead to fibrosis. 

The new findings “bring the hepatic stellate cell into the 

picture,” senior author George Kunos, senior investigator at 

the National Institute on Alcohol Abuse and Alcoholism, 

told BioWorld. “So far, it had not been implicated in the 

development of fatty liver.” 

As receptor families go, the endocannabinoid one is small – 

as of now it consists of just two members: CB1 and CB2. 

CB1 receptors are found in the nervous system and in the 

liver, while CB2 receptors are associated mainly with inflammatory 

and immune cells. 

The researchers were spurred to investigate whether endocannabinoids 

are involved in fatty liver disease because 

alcoholic fatty liver has similarities to fatty liver induced by 

a high-fat diet, where endocannabinoids play a role. When 

Kunos and his team fed animals a diet consisting mainly of 

alcohol, they found that hepatic stellate cells developed elevated 

levels of 2-arachidonoylglycerol or 2-AG, one of the 

two ligands for CB1 receptors. When the hepatic stellate 

cells secrete that 2-AG, it stimulates the CB1 receptors on 

hepatocytes in the vicinity. “The actual accumulation of fat 

occurs on the hepatocyte,” Kunos said, and leads to liver 

damage. The specificity of alcohol’s effect on both 2-AG 

and hepatic stellate cells, Kunos noted, were surprising, 

since “there is no known specific receptor target for 

alcohol.” The researchers showed that neither alcohol nor 

its metabolites had an effect on isolated hepatic stellate 

cells, and alcohol metabolites did not lead to the development 

of fatty liver. Together, Kunos said, the results suggested 

that the effect of alcohol on stellate cells in vivo is an 

indirect one, possibly mediated by bacterial endotoxin – 

though he noted that the endotoxin connection is “speculative” 

at this point. 

To make sure that the effects they were seeing were due to 

endocannabinoid action directly on liver cells, rather than in 

the brain, the researchers generated a knockout mouse that 

lacked CB1 receptors specifically in the liver. Such mice did 

not develop fatty liver disease on a high-alcohol diet. “The 

brain can influence liver metabolism through the autonomic 

nervous system,” Kunos explained. The appetite regulator 

leptin, for example, influences the way the liver metabolizes 

carbohydrates – but leptin’s site of action is in the 

brain. “It may still be that the central nervous system contributes” 

to the altered fat metabolism that leads to fatty 

liver, Kunos said. But the effect of deleting CB1 receptors 

on the hepatocytes shows that liver receptors play an 

important role in the effect. 

The researchers then treated another group of mice with 

the endocannabinoid blocker Acomplia (rimonabant, 

Sanofi-Aventis Group) and found that those mice, too, were 

protected from fatty liver disease due to excess alcohol. 

“The present findings suggest that treatment with a CB1 

antagonist may slow the development of fatty liver and 

thus prevent or delay its progression to more severe and 

irreversible forms of liver disease.” 

Kunos also noted that the findings might give a shot in the 

arm to the U.S. prospects of endocannabinoid antagonists 

for the treatment of obesity-related fatty liver. Rimonabant, 

the drug used in the Cell Metabolism study, is approved in 

the European Union, but has yet to gain FDA clearance, 

partly because of concern with side effects that are due to 

the drug’s action on brain receptors. But if new types of 

antagonists are developed that do not cross the blood-brain 

barrier, they might have promise for the treatment of fatty 

liver regardless of its origin. 


106 

New Research Implicates 

Lipid Metabolites in Insulin Resistance 

The news that tighter control of blood sugar levels appears 

to increase deaths in a large clinical study hit like a bomb in 

February 2008, a stark reminder of just how much remains 

to be learned about the metabolic complexities of diabetes. 

The National Heart, Lung, and Blood Institute stopped one 

treatment in a large, ongoing clinical trial of diabetes and 

cardiovascular disease 18 months early due to safety concerns 

after review of available data, although the study will 

continue. In the trial of adults with Type II diabetes at especially 

high risk for heart attack and stroke, the strategy of 

intensively lowering blood glucose below current recommendations 

actually increased the risk of death compared 

with a less-intensive standard treatment strategy. 

Those metabolic complexities continue to be unraveled at 

the basic science level. In the Feb 8, 2008, issue of Cell, 

researchers from the Karolinska Institute in Sweden, the 

University of Kuopio in Finland and the University of Utah 

reported that high levels of blood sugar can lower levels of 

an enzyme that is involved in intracellular fat metabolism, 

setting off an intracellular cascade that contributes to Type 

II diabetes symptoms such as insulin resistance and obesity. 

The authors focused on the enzyme, called diacylglycerol 

kinase, because in a pilot gene expression profiling study, 

they found that diacylglycerol kinase is downregulated in 

the muscles of Type II diabetics, but only if they have poor 

blood sugar control. “That was an eye-opener for us,” senior 

author Juleen Zierath told BioWorld. 

The scientists studied diacylglycerol kinase expression in 

muscle biopsies from 10 diabetics and 11 controls, and 

found that skeletal muscle expression of the delta type was 

specifically reduced in the diabetics. The authors next went 

to animal studies to work out the kinase’s mechanism and 

its relationship to glucose and insulin in more detail. They 

first compared normal rats to those that have a form of 

Type II diabetes, and found that the diabetic animals had 

low levels of skeletal DGK delta, and that those levels 

increased when their diabetes was treated. 

Liver levels of both treated and untreated diabetic rats were 

similar to each other and to normal controls. Zierath said 

that other types of the kinase may be important in the liver, 

and also that such specificity is typical for abnormalities that 

contribute to diabetes: “to regulate glucose . . . multiple 

organs play a role,” Zierath explained. “All of these tissues 

work together like an orchestra – though no one really 

knows who the conductor is.” But what is clear is that diabetics 

have trouble with glucose uptake. 

Because there are no pharmacological inhibitors of diacylglycerol 

kinase that are specific to the delta isoform, the 


researchers next bred knockout mice that were missing one 

copy of the kinase, giving them half the normal level of the 

protein. At nearly 40 percent, diabetic patients had a similar 

reduction in DGK delta levels. Since the symptoms of 

Type II diabetes tend to appear with age – though the age 

they appear at has been getting younger as exercise and 

nutritional habits have been getting poorer – the mice were 

tested at two different ages for their insulin levels, ability to 

metabolize glucose and their ability to transport glucose. 

Nine-week old mice with low DGK delta levels were somewhat 

less sensitive to insulin, but still showed normal 

metabolism in many respects. Older mice had a wider variety 

of problems, including more abnormalities in insulin signaling 

and obesity. 

The animals also had metabolic inflexibility, meaning they 

were impaired at switching between using glucose and fat 

for energy. Typically, glucose will be used for energy when 

it is available, while fat is used for energy when it’s not. But 

animals with low levels of DGK delta were impaired at making 

that switch. “When they are fasted, they are not able to 

switch into the fat [metabolism] pathway,” Zierath said. 

And that means the fat is not used, contributing to obesity. 

At the molecular level, DGK delta is involved in metabolizing 

intracellular fats, and when its levels are low, those fats 

build up. The fats, in turn, activate protein kinase C, which 

decreases glucose uptake into the skeletal muscle. 

Overall, the data suggested that increasing the activity of 

DGK delta could help ameliorate the consequences of Type 

II diabetes. Zierath said that the best way to do so would be 

the old-fashioned one: exercise. But the findings also provided 

pharmacological attack points, though Zierath 

pointed out that any such approach would still need “serious 

biological validation” in further studies. Still, the pathway 

could provide drug targets for those who can’t or 

won’t exercise. Zierath said that going downstream to the 

fats themselves or protein kinase C, whose levels are 

increased, would probably be a more promising strategy 

than targeting diacylglycerol kinase delta directly. “It’s 

always harder to activate something – you want to find an 

inhibitor if you can.” 

$50M Sequence Project to 

Map Genomes in 1,000 People 

The industry was promised a treasure trove of targets by a 

January 2008 sequencing effort, the $50 million 1000 

Genomes Project, launched by an international public sector 

consortium. The project draws on sequence data from 

at least 1,000 people from around the world to create the 

most detailed, and it is hoped, medically relevant picture of 

human genetic variation relating to common diseases and 

responses to drugs. It is driven by the recent successes of 

genomewide association studies in finding genes for dis-

eases such as Type I diabetes and Crohn’s disease, and 

uncovering genetic links between disorders such as obesity 

and three genes involved in Type II diabetes. The three-year 

project will make its findings available free through public 

databases. The major funders are the Wellcome Trust 

Sanger Institute in Cambridge, UK, the U.S. National 

Institutes of Health’s National Human Genome Research 

Institute (NHGRI) and the Beijing Genomics Institute in 

China. 

A dramatic fall in the cost of sequencing and accompanying 

advances in bioinformatics have made the 1000 

Genomes Project possible. It builds, of course, on the 

Human Genome Project, and on other recent studies of 

human genetic variation, such as HapMap, the international 

effort to plot all human variation, and the Wellcome 

Trust’s Case Control Consortium’s genome association studies. 

But those look like paltry efforts compared to the scale 

of the 1000 Genomes Project, which will sequence 6 trillion 

DNA bases, generating 60 times more data over three years 

than have been deposited into public DNA databases over 

the past 25 years. “When up and running at full speed, this 

project will generate more sequence data in two days than 

was added to public databases for all the past year,” said 

Gil McVean of Oxford University, one of the co-chairs of the 

project. 

HapMap, the Case Control Consortium and similar programs 

have pinpointed more than 100 regions of the 

genome containing variants associated with diseases 

including diabetes, cardiovascular disease and inflammatory 

bowel disease. But to find the precise variants, it still is necessary 

to do time-consuming DNA sequencing. The 1000 

Genomes Project will enable researchers to zoom in on disease-related 

polymorphisms far more quickly. The overall 

goal is to produce a catalog of variants that are present at 

1 percent or greater frequency across the genome, down to 

0.5 percent within genes. The 1,000 people who contribute 

their DNA will be anonymous. There will be no accompanying 

medical information, since the aim is to produce a map 

of genetic variants. 

Francis Collins, director of NHGRI, said that once the work 

is complete, it will increase the ability to find genetic vari- 

ants underpinning disease by five times across the genome 

and tenfold within gene regions. “Our existing databases 

do a reasonably good job of cataloguing variation found in 

at least 10 percent of a population. . . . We hope to give 

biomedical researchers a genome-wide map down to the 1 

percent level.” 

Currently, rare gene variants that have a severe effect, such 

as Huntington’s disease, are tracked down through family 

studies, while genomewide association studies can pick up 

the common variants that are related to common diseases. 

But between the rare and the common sits a broad range 

of diseases, which it is hoped will be covered by the 1000 

Genomes Project. 

In addition to covering all single nucleotide polymorphisms, 

the project will map structural variants that are now 

thought to be implicated in mental retardation and autism. 

Study Relates Gastric Surgery to Diabetes 

In an early 2008 world-first study by Monash University, of 

Melbourne, Australia, researchers found gastric banding 

surgery has a profound impact on diabetes. The study, published 

in The Journal of the American Medical Association, 

found obese patients with Type II diabetes who underwent 

gastric banding were five times more likely to have their diabetes 

move into long-term remission, compared with 

patients who engaged in conventional weight loss therapies, 

such as a controlled-calorie diet and exercise. 

The four-year study, which was led by John Dixon, and Paul 

O’Brien, of Monash University’s Center for Obesity Research 

and Education, monitored 60 volunteers for two years who 

underwent significant weight loss of more than 10 percent 

of their body weight. Dixon said of those who underwent 

gastric banding surgery, 73 percent achieved remission for 

Type II diabetes, compared to just 13 percent of the people 

who underwent conventional therapy. “Our study presents 

strong evidence that obese patients with a BMI greater than 

30 with Type II diabetes need to lose a significant amount 

of weight to improve their overall health and glycemic management,” 

Dixon said. “[The] study shows that gastric 

banding surgery can assist those patients to achieve this – 

and with sustained results.” 


108 


Personal Health Expenditures, by Source of Funds and Type, U.S. 2006 

Obesity as a Function of Income and Education 

Obesity, BMI>30 (percent) 

30 

25 

20 

15 

10 

5 

0 

Medicare 

21.6% 

Other 

government 

7.5% 

Medicaid 

16.2% 

Out-of-pocket 

payments 

14.6% 

Private health 

insurance 

36% 

400 

Income (percent of poverty) 

Men Women 

Expenditures: $1.8 trillion 

Other private funds 

4.1% 

Nursing 

home 

$124.9B 

OBESITY DATA 

Source: Adam Drewnowski and S.E. Specter, “Poverty and obesity: the role of energy density and energy costs,” The American 

Journal of Clinical Nutrition, Vol. 79, No. 1, p. 6-16, January 2004. 

Obesity, BMI>30 (percent) 

Prescription 

drugs 

$216.7B 

Source of Funds Type of Expenditures 

Source: Centers for Medicare & Medicaid Services, Office of the Actuary, National Health Statistics Group, National Health 

Expenditure Accounts. 

30 

25 

20 

15 

10 

5 

0 

Other 

$324.6B 

Physician 

services 

$447.6B 

Hospital 

$648.2B 

16 


110 

Obesity and Type II Diabetes 


Insulin Sensitivity Improves with Weight Loss in 

Patients with Type II Diabetes 

Strength of Evidence on Lifestyle Factors and Risk of 

Developing Type II Diabetes 

Evidence Decreased risk Increased risk 

Convincing Voluntary weight loss in Overweight and obesity 

overweight and obese Abdominal obesity 

people Physical inactivity 

Physical activity Maternal diabetesa 

Probable Non-starch polysaccharides Saturated fats 

Intrauterine growth retardation 

Possible n-3 fatty acids Total fat intake 

Low glycaemic index foods Trans fatty acids 

Exclusive breastfeeding 

Insufficient Vitamin E Excess alcohol 

Chromium 

Magnesium 

Moderate alcohol 

Source: World Health Organization.

Strength of Evidence on Lifestyle Factors and the Risk of 

Developing Cancer 

Evidence Decreased risk Increased risk 

Convincing Physical activity Overweight and obesity 

Alcohol 

Aflatoxin 

Chinese-style salted fish 

Probablea Fruits and vegetables Preserved meat 

Physical activity Salt-preserved foods and 

salt 

Very hot drinks and food 

Possible/insufficient Fibre Animal fats 

Soya Heterocyclic amines 

Fish Polycyclic aromatic 

n-3 Fatty acids hydrocarbons 

Carotenoids Nitrosamines 

Vitamins B2, B6, folate, 

B12, C, D, E 

Calcium, zinc and selenium 

Non-nutrient plant constituents 


Obesity, Cancer and Cardiovascular Disease 

Strength of Evidence on Lifestyle Factors and Risk of Developing Cardiovascular Diseases 

Evidence Decreased risk No relationship Increased risk 

Convincing Regular physical activity Vitamin E supplements Myristic and palmitic acids 

Linoleic acid Trans fatty acids 

Fish and fish oils (EHA and High sodium intake 

DHA) Overweight 

Vegetables and fruits High alcohol intake (for stroke) 

(including berries) 

Potassium 

Low to moderate alcohol 

intake (for coronary heart 

disease) 

Probable a-Linolenic acid Stearic acid Dietary cholesterol 

Oleic acid Unfiltered boiled coffee 

Non-starch polysaccharides 

Wholegrain cereals 

Nuts (unsalted) 

Plant sterols/stanols 

Folate 

Possible Flavonoids Fats rich in lauric acid 

Soy products Impaired fetal nutrition 

Beta-carotene supplements 

Inufficient Calcium Carbohydrates 

Magnesium Iron 

Vitamin C 



112 

CDC’s Recommended Community Strategies to Prevent Obesity in the U.S. 

Strategies to Promote the Availability of Affordable Healthy Food and Beverages 

Strategy 1 Communities should increase availability of healthier food and beverage choices in public service 

venues. 

Suggested A policy exists to apply nutrition standards that are consistent with the dietary guidelines for Americans (US 

measurement Department of Health and Human Services, US Department of Agriculture. Dietary guidelines for Americans. 6th 

ed. Washington, DC: U.S. Government Printing Office; 2005.) to all food sold (e.g., meal menus and vending 

machines) within local government facilities in a local jurisdiction or on public school campuses during the 

school day within the largest school district in a local jurisdiction. 

Strategy 2 Communities should improve availability of affordable healthier food and beverage choices in public 

service venues. 

Suggested A policy exists to affect the cost of healthier foods and beverages (as defined by the Institute of Medicine [IOM] 

measurement [Institute of Medicine. Preventing childhood obesity: health in the balance. Washington, DC: The National 

Academies Press; 2005]) relative to the cost of less healthy foods and beverages sold within local government 

facilities in a local jurisdiction or on public school campuses during the school day within the largest school 

district in a local jurisdiction. 

Strategy 3 Communities should improve geographic availability of supermarkets in underserved areas. 

Suggested The number of full-service grocery stores and supermarkets per 10,000 residents located within the three largest 

measurement underserved census tracts within a local jurisdiction. 

Strategy 4 Communities should provide incentives to food retailers to locate in and/or offer healthier food and 

beverage choices in underserved areas. 

Suggested Local government offers at least one incentive to new and/or existing food retailers to offer healthier food and 

measurement beverage choices in underserved areas. 

Strategy 5 Communities should improve availability of mechanisms for purchasing foods from farms. 

Suggested The total annual number of farmer-days at farmers' markets per 10,000 residents within a local jurisdiction. 

measurement 

Strategy 6 Communities should provide incentives for the production, distribution, and procurement of foods 

from local farms. 

Suggested Local government has a policy that encourages the production, distribution, or procurement of food from local 

measurement farms in the local jurisdiction. 

Strategies to Support Healthy Food and Beverage Choices 

Strategy 7 Communities should restrict availability of less healthy foods and beverages in public service venues. 

Suggested A policy exists that prohibits the sale of less healthy foods and beverages (as defined by IOM [Institute of 

measurement Medicine. Preventing childhood obesity: health in the balance. Washington, DC: The National Academies Press; 

2005]) within local government facilities in a local jurisdiction or on public school campuses during the school 

day within the largest school district in a local jurisdiction. 

Strategy 8 Communities should institute smaller portion size options in public service venues. 

Suggested Local government has a policy to limit the portion size of any entree (including sandwiches and entrée salads) by 

measurement either reducing the standard portion size of entrees or offering smaller portion sizes in addition to standard portion 

sizes within local government facilities within a local jurisdiction. 

Strategy 9 Communities should limit advertisements of less healthy foods and beverages. 

Suggested A policy exists that limits advertising and promotion of less healthy foods and beverages within local governmeasurement 

ment facilities in a local jurisdiction or on public school campuses during the school day within the largest school 

district in a local jurisdiction. 

Strategy 10 Communities should discourage consumption of sugar-sweetened beverages. 

Suggested Licensed child care facilities within the local jurisdiction are required to ban sugar-sweetened beverages, includmeasurement 

ing flavored/sweetened milk and limit the portion size of 100% juice. 

Strategy to Encourage Breastfeeding 

Strategy 11 Communities should increase support for breastfeeding. 

Suggested Local government has a policy requiring local government facilities to provide breastfeeding accommodations for 

measurement employees that include both time and private space for breastfeeding during working hours. 


CDC’s Recommended Community Strategies to Prevent Obesity in the U.S., cont. 

Strategies to Encourage Physical Activity or Limit Sedentary Activity Among Children and Youth 

Strategy 12 Communities should require physical education in schools. 

Suggested The largest school district located within the local jurisdiction has a policy that requires a minimum of 150 minmeasurement 

utes per week of PE in public elementary schools and a minimum of 225 minutes per week of PE in public mid 

dle schools and high schools throughout the school year (as recommended by the National Association of Sports 

and Physical Education). 

Strategy 13 Communities should increase the amount of physical activity in PE programs in schools. 

Suggested The largest school district located within the local jurisdiction has a policy that requires K--12 students to be 

measurement physically active for at least 50% of time spent in PE classes in public schools. 

Strategy 14 Communities should increase opportunities for extracurricular physical activity. 

Suggested The percentage of public schools within the largest school district in a local jurisdiction that allow the use of 

measurement their athletic facilities by the public during non-school hours on a regular basis. 

Strategy 15 Communities should reduce screen time in public service venues. 

Suggested Licensed child care facilities within the local jurisdiction are required to limit screen viewing time to no more than 

measurement 2 hours per day for children aged =2 years. 

Strategies to Create Safe Communities That Support Physical Activity 

Strategy 16 Communities should improve access to outdoor recreational facilities. 

Suggested The percentage of residential parcels within a local jurisdiction that are located within a half-mile network dismeasurement 

tance of at least one outdoor public recreational facility. 

Strategy 17 Communities should enhance infrastructure supporting bicycling. 

Suggested Total miles of designated shared-use paths and bike lanes relative to the total street miles (excluding limited 

measurement access highways) that are maintained by a local jurisdiction. 

Strategy 18 Communities should enhance infrastructure supporting walking. 

Suggested Total miles of paved sidewalks relative to the total street miles (excluding limited access highways) that are 

measurement maintained by a local jurisdiction. 

Strategy 19 Communities should support locating schools within easy walking distance of residential areas. 

Suggested The largest school district in the local jurisdiction has a policy that supports locating new schools, and/or repairmeasurement 

ing or expanding existing schools, within easy walking or biking distance of residential areas. 

Strategy 20 Communities should improve access to public transportation. 

Suggested The percentage of residential and commercial parcels in a local jurisdiction that are located either within a 

measurement quarter-mile network distance of at least one bus stop or within a half-mile network distance of at least one 

train stop (including commuter and passenger trains, light rail, subways, and street cars). 

Strategy 21 Communities should zone for mixed use development. 

Suggested Percentage of zoned land area (in acres) within a local jurisdiction that is zoned for mixed use that specifically 

measurement combines residential land use with one or more commercial, institutional, or other public land uses. 

Strategy 22 Communities should enhance personal safety in areas where persons are or could be physically active. 

Suggested The number of vacant or abandoned buildings (residential and commercial) relative to the total number of 

measurement buildings located within a local jurisdiction. 

Strategy 23 Communities should enhance traffic safety in areas where persons are or could be physically active. 

Suggested Local government has a policy for designing and operating streets with safe access for all users which includes 

measurement at least one element suggested by the national complete streets coalition (http://www.completestreets.org) 

Strategy to Encourage Communities to Organize for Change 

Strategy 24 Communities should participate in community coalitions or partnerships to address obesity. 

Suggested Local government is an active member of at least one coalition or partnership that aims to promote environmenmeasurement 

tal and policy change to promote active living and/or healthy eating (excluding personal health programs such as 

health fairs). 

Source: Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report, July 24, 2009, “Recommended 

Community Strategies and Measurements to Prevent Obesity in the United States.” 


114 

Obesity and Depression 

Relation Between Obesity and Depression 

Number of % with DIS/DSM-III Depression in the Past Month 

Relative Body Weight Participants All Respondents Females Males 

Normal weight 4,154 2.79 3.82 1.67 

Underweight 301 3.24 3.82 1.82 

Overweight 2,297 2.42 4.01 1.37 

Obese 1,658 5.12 6.74 2.85 

Obesity class 1 910 3.55 4.97 1.88 

Obesity class 2 410 4.8 6.79 0.83 

Obesity class 3 267 12.51 13.03 11.54 

Source: Third National Health and Nutrition Examination Survey, 1988-1994. 


Percentage of Obese Subjects Reporting Depression 

Depressed in 1994 

Value No. N % 

Obesity in 1994 Obese 325 41 12.6 

Nonobese 1561 97 6.2 

Source: International Journal of Obesity, R. E. Roberts, S. Deleger, W. J. Strawbridge 

and G. A. Kaplan, “Prospective association between obesity and depression: evidence 

from the Alameda County Study,” (2003) 27, 514–521. 

Percentage of People Who Are Depressed, by Relative 

Body Weight 

14 

12 

10 

8 

6 

4 

2 

0 

Normal 

Weight 

Underweight 

Overweight Obese Obesity Obesity 

Class 1 Class 2 

Source: Third National Health and Nutrition Examination Survey, 1988-1994. 

Obesity 

Class 3

Is Obesity an Epidemic in the U.S.? 

% Yes 

Total 85 

White 85 

African-American 85 

Hispanic 85 

Men 81 

Women 89 

Ages 18-29 89 

Ages 30-39 84 

Ages 40-49 86 

Ages 50-64 84 

Ages 65+ 85 

High school or less 81 

Some college/post high school 89 

College graduate 85 

Less than $30,000/yr household 84 

$30,000-$50,000/yr household 88 

$50,000-$75,000/yr household 87 

More than $75,000/yr household 86 

Democrat 87 

Independent 85 

Republican 84 

Northeast 86 

Central 84 

South 84 

West 87 

Source: Trust for America’s Health and the Robert Wood Johnson Foundation. 

Higher Health Care Costs for Businesses 

On average, obese workers have up to 21 percent higher health care costs compared to normal weight employees. It is estimated 

that in 1994, obesity cost U.S. businesses $12.7 billion, of which physical inactivity accounted for $7.7 billion. 

In 2000 alone, physically inactive members cost Blue Cross and Blue Shield of Minnesota (BCBSMN) a total of $83.6 million (or 

$56 for every member) per year. In addition, “almost one third (31 percent) of costs related to heart disease, stroke, colon cancer, 

and osteoporosis” in the BCBSMN population were attributable to physical inactivity. 

Higher health care costs for obese and sedentary workers signal poorer overall health among these individuals. And given poorer 

health, lower worker productivity and increased absenteeism are more likely among obese and physically inactive employees. 

Lower Worker Productivity and Increased Absenteeism 

Researchers found that obese workers had 183.63 lost workdays per 100 full time employees, compared to normal weight workers 

who had 14.19 lost workdays per 100 full time employees. 

A 2004 study concluded that excessive weight and physical inactivity negatively impact the quality of work performed, the quantity 

of work performed and overall job performance among obese, sedentary individuals. 

Higher Workers’ Compensation Claims 

A number of studies have shown obese workers have higher workers’ compensation claims. 

A 2007 study found that excessive weight gain among employees is related to higher amounts of workers’ compensation claims. 

Obese workers had on average 11.65 claims per 100 full time employees, compared to normal weight employees who had 5.80 

claims per 100 full time employees. 

The cost of claims for obese employee workers’ compensation claims were also significantly higher. Obese employees had 

$51,091 in medical claims costs per 100 full time employees, compared to only $7,503 in medical claims costs for normal weight 

workers. And obese workers had $59,178 in indemnity claims costs per 100 full time employees, compared to only $5,396 in 

indemnity claims costs for normal weight employees. 



116 

What’s Behind the Obesity Epidemic? 

MANY ISSUES INFLUENCE NUTRITION AND PHYSICAL ACTIVITY BEHAVIORS 

Food Choices and Changes 

Higher caloric intake – Adults consumed approximately 300 

more calories daily in 2002 than they did in 1985. 

Higher caloric density of foods. 

Limited access to supermarkets and nutritious, fresh foods in 

many urban and rural neighborhoods. 

“Portion distortion,” or the rise of bigger portions. 

“Value sizing” or placing a higher value on the amount of 

food versus the quality of food. 

Less in-home cooking and more frequent reliance on take-out 

food and eating in restaurants. 

The proliferation of microwaves and faster, easier to prepare 

foods. 

Schools 

A variety of food and beverage options are available throughout 

the school day including soda, fruit drinks that are not 100 

percent juice, and foods that are high in calories, fat and sodium, 

but low in nutritional value. These foods and beverages are 

available at venues such as a la carte lines, school stores, vending 

machines, fundraisers and classroom parties. 

Reduction in the amount of physical education, recess and 

recreation time. 

Few safe routes to school that encourage kids to walk and 

bike. 

Limited health education classes. 

Lack of opportunities to participate in physical activity. 

Communities Design 

Communities designed to foster driving rather than walking 

or biking. 

Lack of public transportation options. 

No sidewalks or poor upkeep of sidewalk infrastructure. 

Walking areas often unsafe or inconvenient. 

Limited parks and recreation space, including indoor facilities. 

Poor upkeep and security in local parks. 

Lack of affordable indoor physical activity options. 

RISK FACTORS AND OTHER ISSUES THAT AFFECT WEIGHT GAIN 

Genetics, Physiology, and Life Stages 

Metabolism. 

Childbearing. 

Increased risk factors for obesity and related diseases in children 

with obese parents, particularly mothers. 

Aging factors, including menstruation, premenopause and 

menopause for women. 

Weight-gain as a side effect from some commonly used medications 

such as insulin, antiretrovirals, antidepressants, oral 

contraceptives and injectable contraceptives. 

Psychology 

Body image concerns. 

Consumers’ frustration with conflicting nutrition information 

and advice. 

Eating to combat stress. 

Turning to eating as a replacement for smoking 

or other unhealthy behaviors. 



Marketing and Advertising 

More advertising and marketing of unhealthy foods, particularly 

to kids. 

Marketing of “fad” diets. 

Workplaces Not Conducive to Health 

Many desk jobs limit or discourage activity, part of the sedentary 

lifestyle. 

Worksites typically not designed to foster movement. 

Limited opportunities for physical activity or recreation during 

the work day. 

Unhealthy options in cafeterias or work lunch sites. 

Lack of bike racks and/or shower facilities discourage active 

transportation. 

Economic Constraints 

Health insurance coverage for obesity-prevention services is 

often limited or not available. 

People without health insurance often do not receive either 

appropriate preventive services or follow-up care. 

“Value sizing” of less nutritious foods, and the higher costs of 

many nutritious foods. 

Expense of and taxes on gym memberships, exercise classes, 

equipment, facility use and sports league fees. 

Lower-income neighborhoods have fewer and smaller grocery 

stores and less access to affordable fruits and vegetables. 

Family and Home Influences 

Influence of other family members’ habits on eating and exercise 

patterns. 

“Electronic culture” options for entertainment and free time, 

including TV, video games and the Internet. 

More people working outside the home or far from home. 

Limited Time 

Long work hours mean more meals – many of them high in 

calories – are eaten outside of the home. 

Car time and commuting cut into free time that could be 

used for physical activity. 

The Environment and Obesity 

Recent studies show a potential link between exposure to 

chemicals used in plastics and childhood obesity. Two separate 

studies of children in East Harlem and surrounding areas found 

that the chemical phthalates are an endocrine disruptor. 

Phthalates are absorbed into the body and then affect glands 

and hormones that regulate many bodily functions. In order to 

measure the amount of exposure researchers tested the levels 

in the children’s urine, and they found that the heaviest children 

had the highest levels of phthalate. The study also 

revealed levels of phthalates significantly higher than the average 

levels in children across the U.S. 

The findings of the study do not prove that the chemicals 

definitively cause obesity, nor did they find a causal connection, 

but they do show a link between phthalates and obesity. This 

link points to the importance of understanding and investigating 

how environmental factors can affect health.

Health Care Costs of Obesity 

Obesity costs the nation $75 billion in direct costs each year, while the total cost of obesity, including indirect costs, is as high as 

$139 billion per year. 

Indirect costs often fall most heavily on employers in the form of increased absenteeism, disability, presenteeism (when 

employees come to work in spite of illness, which can have similar negative repercussions on business performance) and 

workers’ compensation. 

Obesity-related annual costs for treating children more than tripled between 1979 and 1999. 

Projections for health care costs attributable to obesity and overweight are that they will more than double every decade. By 

2030, according to one study, health care costs attributable to obesity and overweight could range from $860 billion to $956 billion, 

which would account for 15.8 to 17.6 percent of total health care costs, or one in every six dollars spent on health care. 

A 2008 study reported that obese employees cost private employers approximately $45 billion a year as a result of medical 

expenses and excessive absenteeism. 

Obese people pay 36 percent more for health care and 77 percent more for medication when compared with normal-weight 

people. These increases are higher than the costs associated with smoking or drinking. 

Lower Worker Productivity and Increased Absenteeism 

Researchers found that obese workers had 183.63 lost workdays per 100 full-time employees, compared with normal-weight 

workers, who had 14.19 lost workdays per 100 full-time employees. 

As a person’s BMI increases, so do the number of sick days, medical claims and health care costs. 

A 2004 study concluded that excessive weight and physical inactivity negatively impact the quality of work performed, the quantity 

of work performed and overall job performance among obese, sedentary individuals. 

Higher health care costs for obese and sedentary workers signal poorer overall health among these individuals. And given poorer 

health, lower worker productivity and increased absenteeism are more likely among obese and physically inactive employees. 

Higher Workers’ Compensation Claims 

Several studies have shown obese workers have higher workers’ compensation claims. The cost of workers’ compensation claims 

by obese employees were also significantly higher. Obese employees had $51,091 in medical claims costs per 100 full-time employees, 

compared with only $7,503 in medical claims costs for normal weight workers. And obese workers had $59,178 in indemnity 

claims costs per 100 full-time employees, compared with only $5,396 in indemnity claims costs for normal weight employees. 

Occupational Health and Safety Costs 

The number of severely obese (BMI > 40) patients quadrupled between 1986 and 2000 from one in 200 to one in 50. The number 

of super-obese (BMI > 50) patients grew by a factor of five, from one in 2,000 to one in 400. Emergency responders and 

health care providers face unique challenges in transporting and treating the heaviest patients. 

A typical ambulance outfitted with equipment and two emergency medical technicians (EMTs) that can transport a 400-pound 

patient costs $70,000. A specially outfitted bariatric ambulance that can transport patients weighing up to 1,000 pounds costs 

$110,000. 

A standard hospital bed can hold 500 pounds and costs $1,000. A bariatric hospital bed that can hold up to 1,000 pounds costs 

$4,000. 

Nearly one in two emergency medical technicians sustained a back injury while performing EMS duties. Most blamed lifting 

extremely obese patients. 



118 

Obesity’s Impact on Health 

HEALTH IMPACT OF OBESITY AND PHYSICAL INACTIVITY 

Below are some key findings based on a range of research into the 

health impact of obesity. Physical activity has been shown to have a 

role in reversing or preventing many of these health problems. 

Type II Diabetes 

Over the past 10 years, the number of newly diagnosed diabetes 

cases in the U.S. nearly doubled from 4.8 per 1,000 in 1995-1997 

to 9.1 per 1,000 in 2005-2007. 

80 percent of those with Type II diabetes are overweight. 

More than 20 million adult Americans have diabetes. 

Another 57 million Americans are prediabetic, which means 

they have prolonged or uncontrolled elevated blood sugar levels 

that can contribute to the development of diabetes. 

Diabetes is the seventh leading cause of death in the U.S. and 

accounts for 11 percent of all U.S. health care costs. 

CDC projects that 48.3 million Americans will have diabetes by 

2050. 

About 176,500 individuals under the age of 20 have diabetes. 

Two million adolescents aged 12-19 have prediabetes. 

The National Institute of Diabetes and Digestive and Kidney 

Diseases found that a 7 percent weight loss together with moderate 

levels of physical activity (walking 30 minutes a day, five 

days a week) decreased the number of new Type II diabetes cases 

by 58 percent among people at-risk for diabetes. 

Heart Disease and Stroke 

People who are overweight are more likely to suffer from high 

blood pressure, high levels of blood fats and LDL (or bad cholesterol), 

which are all risk factors for heart disease and stroke. 

Physically inactive people are twice as likely to develop coronary 

heart disease as regularly active people. 

Heart disease is the leading cause of death in the U.S., and 

stroke is the third leading cause. 

One in four Americans has some form of cardiovascular disease. 

Heart disease can lead to a heart attack, congestive heart failure, 

sudden cardiac death, angina or abnormal heart rhythm. 

A stroke limits blood and oxygen to the brain and can cause 

paralysis or death. 

One in three adults has high blood pressure. Roughly 30 percent 

of cases of hypertension may be attributable to obesity, and in men 

under 45 years of age, the figure may be as high as 60 percent. 

Cancer 

People who are overweight “may increase the risk of developing 

several types of cancer, including cancers of the colon, esophagus 

and kidney. Overweight is also linked with uterine and postmenopausal 

breast cancer in women.” 

Approximately 20 percent of cancer in women and 15 percent 

of cancer in men is attributable to obesity. 

Cancer is the second leading cause of death in the U.S. It is 

unknown why being overweight can increase cancer risk. One theory 

is that fat cells may affect overall cell growth in a person’s body. 

Neurological and Psychiatric Diseases 

Obesity may increase adults’ risk for having dementia. A review 

of 10 published studies found that people who were obese at 

the beginning of the studies were 80 percent more likely to later 

develop Alzheimer’s disease than those adults who had a normal 

weight at enrollment. 


An analysis of data from a health survey of more than 40,000 

Americans found a correlation between depression and obesity. 

According to the results, obese adults were more likely to suffer 

from depression, anxiety and other mental health conditions than 

normal-weight adults. The odds of suffering from any mood disorder 

rose by 56 percent among obese individuals and doubled 

among the extremely obese. 

Kidney Disease 

Obese individuals are 83 percent more likely to develop kidney 

disease than normal-weight individuals, while overweight individuals 

are 40 percent more likely to develop kidney disease. 

An estimated 24.2 percent of kidney disease cases among U.S. 

men and 33.9 percent of cases among women are related to 

overweight and obesity. 

Arthritis 

Obesity is a known risk factor for the development and progression 

of osteoarthritis of the knee and possibly of other joints. 

For example, obese adults are up to four times more likely to 

develop osteoarthritis of the knee than normal-weight adults. 

Among individuals who have received a doctor’s diagnosis of 

arthritis, 68.8 percent are overweight or obese. 

For every pound of body weight lost, there is a 4 percent 

reduction in knee joint stress among overweight and obese people 

with osteoarthritis of the knee. 

Obesity and Children’s Health 

Nearly 32 percent of U.S. children and adolescents are overweight 

or obese (at or above the 85th percentile of BMI for age). 

Approximately 60 percent of obese children aged five to 10 

years had at least one cardiovascular disease (CVD) risk factor – 

such as elevated total cholesterol, triglycerides, insulin or blood 

pressure – and 25 percent had two or more CVD risk factors. 

The American Academy of Pediatrics issued new guidelines in 

July 2008 recommending cholesterol screening of children as 

young as age two and adolescents with a family history of high 

cholesterol or heart disease. The new guidelines also recommend 

screening children whose family history is unknown or those who 

have other factors for heart disease including obesity, high blood 

pressure or diabetes. 

Childhood weight problems can lead to complications such as 

elevated blood pressure and cholesterol, joint problems, Type II 

diabetes, gallbladder disease, asthma, depression and anxiety. 

Severely overweight and obese children often suffer from 

depression, anxiety disorders, isolation from their peers, low selfesteem 

and eating disorders. 

The number of fat cells a person has is determined by late adolescence; 

although overweight and obese children can lose 

weight they do not lose the extra fat cells. 

Young girls who are overweight and/or obese suffer a variety of 

significant health consequences, including menstrual disturbances, 

such as early onset menstruation, and are more likely to 

suffer from polycystic ovary syndrome (PCOS). 

Researchers calculated that a ban on fast-food advertising during 

children’s television programming could reduce by 18 percent 

the number of overweight children ages three to 11 and could 

reduce by 14 percent the number of overweight children ages 12 

to 18.

Obesity’s Impact on Health, cont. 

Obesity and Pregnancy 

There is a growing body of evidence documenting the links 

between maternal health conditions, such as obesity and chronic 

diseases and increased risks before, during and after birth. 

Many pregnant women are overweight, obese or have 

diabetes, all of which can have negative effects on the fetus, as 

well as the mother. According to CDC, in 2002 approximately 50 

percent of women of child-bearing age (between 18 and 44) 

were either overweight or obese; 3 percent experienced high 

blood pressure and 9 percent had diabetes. 

Teenage mothers who are obese before pregnancy are four 

times more likely than their normal-weight counterparts to devel- 

MENTAL HEALTH, STRESS AND OBESITY 

Adults 

There is growing evidence documenting the association between 

obesity and poor mental health. Researchers in the Adult and 

Community Health division of CDC analyzed 2006 BRFSS data 

and found that depression and anxiety are associated with obesity. 

Adults currently or previously diagnosed with depression 

were 60 percent more likely to be obese, and those with anxiety 

disorders were 30 percent more likely to be obese than their 

non-depressed counterparts. Adults with depression or anxiety 

were also less likely to engage in regular physical activity. 

A separate study analyzing data from more than 41,000 

Americans who participated in the National Epidemiologic 

Survey on Alcohol and Related Conditions found that adults 

with high BMI (BMI > 30) were more likely to suffer from 

mood, anxiety and personality disorders than people of normal 

weight (18.5 < BMI < 25). Even individuals in the moderately 

overweight category (25 < BMI < 30) were at an elevated risk 

of anxiety disorders compared with those of normal weight. 

The significant associations between obesity and poor mental 

health have led CDC researchers to “suggest that public health 

interventions should address mental and physical health as a 

combined entity and that programs to simultaneously improve 

people’s mental and physical health should be developed and 

implemented.” 

Adolescents 

The National Alliance to Advance Adolescent Health analyzed 

the 2007 YRBSS and found that compared with normal-weight 

students, obese students are 32 percent more likely to have 

actually attempted suicide, to have seriously considered suicide, 

or to have made a plan to attempt suicide. Obese students, 

compared with those of normal weight, are 20 percent more 

likely to have persistent feelings of hopelessness. 

In addition, according to the 2003 National Survey of Children’s 

Health, overweight adolescents, when compared with those 

who were not overweight, had significantly higher odds of having 

parent-reported mental health or behavior problems: 


op gestationa diabetes – a form of diabetes that arises during 

pregnancy and raises a woman’s risk of developing Type II diabetes 

later on. 

CDC and Kaiser Permanente Northwest Center for Health 

Research found in a recent study that obesity during pregnancy is 

associated with an increased use of health care services and 

longer hospital stays. The study of more than 13,000 pregnancies 

found that obese women required more outpatient medications, 

were given more obstetrical ultrasounds and were less likely to 

see nurse midwives or nurse practitioners in favor of physicians. 

Cesarean delivery rates were 45.2 percent for extremely obese 

women, compared with 21.3 percent for normal-weight women. 

60 percent higher odds of having diagnosed anxiety or 

depression; 

40 percent higher odds of having feelings of worthlessness; 

40 percent higher odds of parental concerns about their children’s 

self-esteem; 

70 percent higher odds of being told by a doctor that they 

have behavior problems; 

30 percent higher odds of being withdrawn; and 

40 percent higher odds of bullying others. 

The study concludes that mental health problems must be considered 

in any strategies to address youths who may be obese, 

and that understanding cultural differences among racial and 

ethnic groups must be factored in to public health decisions. 

Stress and Obesity 

A 2007 study found a direct connection between stress and obesity. 

Scientists performing studies on mice found a chain of 

molecular events that link chronic stress with obesity. The study 

found that when stressed and non-stressed mice were fed the 

same high-calorie diet, the stressed mice gained twice as much 

fat. According to the study, the long-term combination of stress 

and a high-fat/high-sugar diet will lead to obesity and metabolic 

syndrome symptoms such as hypertension and glucose intolerance. 

In addition to the traditional methods of weight loss, 

researchers suggested also including stressreduction therapy and 

a neuropeptide Y receptor inhibitor to induce fat “melting.” 

Binge Eating Disorder and Obesity 

Binge eating disorder is a classified psychiatric disorder that 

affects more than seven million adults in the U.S. Binge eating 

is a compulsive pattern of regular bingeing of unusually large 

amounts of food and complete loss of control over one’s eating 

patterns. While less than 3 percent of the general population is 

affected by binge eating disorder, more than 25 percent of 

patients who are obese or seeking help for weight loss have 

reported it. Because long-term weight management is more 

likely in an individual who is able to control eating patterns, 

physicians treating obese patients need to address the behavioral 

and psychological components of binge eating disorders. 


120 

Global Hunger and Foreign Aid 


Global Hunger and Food Statistics 

World Hunger 

6,813,000,000 Total world population 

1,021,000,000 Undernourished people in the world 

1,144,000,000 Overweight people in the world 

340,571,000 Obese people in the world 

19,675 People who died of hunger each day 

9,999,000 people who died of hunger in 20009 

Economics 

$173,968,000 Money spent due to obesity related diseases in the U.S. 

today 

$81,310,000 Money spent on food that is thrown away in the U.S. today 

$3,781,000 Money spent on global food aid today 

$75,639,000 Money spent on weight-loss programs and products in the 

U.S. today 

Food 

90,500 Tons of food wasted in the U.S. today 

18,900 Tons of global food aid provided today 

80 Percentage of harvested corn, grains and soy beans fed to 

livestock in Europe and North America 

78 Percentage of malnourished children who live in countries 

with food surpluses 

90 Percentage of hungriest nations on Earth that are net 

exporters of food to developed nations 

Source: StopTheHunger.com. 

Countries That Received the Most U.S. Foreign Aid in 2008 

(excludes funds related to the wars in Iraq and Afghanistan) 

2000 

1500 

1000 

US$ millions 2500 

500 

0 

Israel 

Egypt 

Pakistan 

Jordan 

Kenya 

South Africa 

Mexico 

Colombia 

Source: Parade, December 14, 2008, citing the U.S. Department of State. 

Nigeria 

Sudan

Number of Undernourished People in the World, 1969/71- 

2009 (in millions of people) 

1200 

1000 

800 

1970 

1972 

1974 

1976 

1978 

1980 

1982 

Source: Food and Agricultural Organization of the United States. 

Global and Regional per Capita Food Consumption 

(kcal per capita per day) 

Region 1964- 1974- 1984- 1997- 2015 2030 

1966 1976 1986 1999 

World 2358 2435 2655 2803 2940 3050 

Developing 2054 2152 2450 2681 2850 2980 

countries 

Near East and 2290 2591 2953 3006 3090 3170 

North Africa 

Sub-Saharan 2058 2079 2057 2195 2360 2540 

Africa 

Latin America 2393 2546 2689 2824 2980 3140 

and Caribbean 

East Asia 1957 2105 2559 2921 3060 3190 

South Asia 2017 1986 2205 2403 2700 2900 

Industrialized 2947 3065 3206 3380 3440 3500 

countries 

Transition 3222 3385 3379 2906 3060 3180 

countries 

Source: World Health Organization, citing World agriculture: towards 2015/2030. 

Food and Agriculture Organization of the United Nations, 2002. 

Undernourishment in 2009, by Region (in millions of people) 

Source: Food and Agricultural Organization of the United States. 

1984 

1986 

1988 

1990 

Undernourishment and Food Consumption 

1992 

1994 

1996 

1998 

2000 

2002 

2004 

2006 

Asia and the Pacific 

Sub-Saharan Africa 

2008 

Latin American and 

the Caribbean 

Near East and North 

Africa 

Developed Countries 


122 

Obesity Deals and Data 

Collaborations Between Biotech and Pharmaceutical Companies 

Biovitrum AB – AstraZeneca plc Agreement for Biovitrum to divest its obesity program to AstraZeneca. AstraZeneca is paying 

$265.6M in the deal, gaining rights to all of Biovitrum's assets relating to the leptin modulator program in obesity (12/21/09) 

Amylin Pharmaceuticals Inc. – Takeda Pharmaceutical Co. Ltd. Agreement to co-develop obesity compounds. Amylin will 

receive $75M up front and could draw more than $1B in additional payments for achieving milestones; the companies will split 

costs related to obtaining U.S. approval 80-20, with Takeda taking on the lion's share; Takeda will cover all costs of obtaining 

approval outside the U.S.; Amylin has the option to co-commercialize the first two approved products in the U.S. and any followon 

products (11/2/09) 

DeveloGen AG – Boehringer Ingelheim GmbH Collaboration in the field of diabetes, obesity and metabolic syndrome and 

other insulin resistance-associated disorders. DeveloGen took $9.5M up front and could earn $321M in milestones, plus tiered 

sales performance payments (5/15/09) 

Biocompatibles International plc – AstraZeneca plc Agreement for a glucagon-like peptide analogue for treating diabetes and 

obesity. The deal is worth a potential $422.6M (12/24/09) 

Galapagos NV – Merck & Co. Inc. Agreement to develop drugs aimed at the obesity and diabetes markets milestones and royalties. 

Galapagos will receive an up-front fee of €1.5M and will take responsibility for the discovery and preclinical work; Merck will 

retain the option to acquire an exclusive license to each drug candidate; Galapagos also may receive milestones that exceed 

€170M ($230.4M), as well as specific sales (1/9/09) 

Marcadia Biotech Inc. – Merck & Co. Inc. Collaboration to jointly discover, develop and commercialize therapies targeting the 

glucagon and related receptors to treat diabetes and obesity. Merck will gain a worldwide license to certain Marcadia development 

candidates and intellectual property, in exchange for an initial up-front fee, as well as payments for exclusivity and ongoing collaborative 

research; Marcadia also will be eligible to receive future milestone and royalty payments and has an option for co- promotion 

(3/6/08) 

Biotechnology Company Deals with Other Biotechnology Companies 

Argenta Discovery Ltd. – Zafgen Inc. Collaboration to use Argenta's computer-aided drug design, medicinal chemistry, assay 

development, in vitro screening, drug metabolism and pharmacokinetics for Zafgen's obesity program. Terms were not disclosed 

(1/29/09) 

Organix Inc. – Galenea Corp. Agreement to develop and commercialize 5-hydroxy-tryptamine 2c serotonin receptor agonists to 

treat obesity and other conditions. Galenea gains worldwide rights in exchange for undisclosed up-front payments, future milestones 

and royalties (10/28/08) 

Zafgen Inc. – Anthill Technologies Inc. Agreement to use Anthill's high-speed chemistry technologies and capabilities for its 

obesity program. Anthill will use its ACOS high-speed synthesis and on-demand purification capabilities to assist Zafgen in the 

development of lead compounds (8/25/08) 

Collaborations Between Biotechnology Companies and Government/Nonprofit Institutions 

Aegis Therapeutics LLC – Albany Medical College Expanded agreement to include a joint commercialization deal for promoting 

clinical development of the college’s obesity peptide drug. Aegis will be responsible for developing an appropriate pharma partnership 

to commercialize the drug in obesity and diabetes indications (8/26/09) 

Sirona Biochem Corp. – National Research Council of Canada Industrial Research Assistance Program Agreement to support 

drug development work in obesity and diabetes. Sirona received a contribution of up to $70,000, and also will receive advisory 

services (9/28/09) 

Znomics Inc. – Oregon Health & Science University Licensing agreement for a genetic model of obesity using the zebrafish. 

The company intends to refine the model for use in the screening of small-molecule compounds; the company also intends to 

identify preclinical drug candidates for obesity (4/15/08) 

Manufacturing, Marketing and Distribution Agreements Between Biotech Companies 

Ventana Biotech Inc. – PE Consortium Ltd. Agreement for a collaboration with PE Consortium, a company that specializes in 

R&D and outsourcing work for obesity drug targets. A deal would enhance Ventana's existing sourcing efforts for obesity treatments 

(8/26/09) 

Terminated Agreements 

GENova Bio-therapeutics Inc. – Bridge Bio-Research plc Terminated relationship to leverage each other's scientific findings. 

GENova focuses on cancer cures, while Bridge acquires drug targets for obesity and Type II diabetes; the agreement was 

announced on Sept. 14 and terminated four days later (9/21/09) 


Obesity Deals and Data, cont. 

Modified Agreements 

Palatin Technologies Inc. – AstraZeneca plc Extended January 2007 collaboration and license agreement to discover, develop 

and commercialize compounds that target melanocortin receptors for obesity and other metabolic disorders. Palatin will receive an 

up-front payment of $1.6M in exchange for additional licenses for compounds and patents; Palatin will be eligible in the near 

future for milestone payments totaling $5M in connection with the collaboration and license agreement (12/9/08) 

Palatin Technologies Inc. – AstraZeneca plc Amended licensing deal to cover additional compounds and intellectual property. 

Palatin inked a $310M deal with Astra-Zeneca to develop small-molecule mel-anocortin-receptor drugs for obesity and other metabolic 

disorders (7/1/08) 

Grants, Contracts and Awards 

Halsa Pharmaceuticals Inc. – Texas Emerging Technology Fund $0.25M grant to continue development and pilot manufacturing 

of a therapeutic treatment for obesity (3/25/08) 

Clinical Trials Update 

7TM Pharma A/S TM30339, a drug designed to work via the Y4 receptor to mimic a natural satiety signal from the gastro-intestinal 

tract involved in the regulation of food, for obesity. Phase Ia data demonstrated the drug was safe and well tolerated with single 

doses; Phase Ib data showed it was safe and well tolerated with 14 days of dosing (2/27/08); Started a Phase I/IIa trial (9/2/08) 

Alizyme plc and Takeda Pharmaceutical Co. Ltd. ATL-962 (cetilistat) for obesity. Started a Phase III study in Japan (12/24/08) 

Amylin Pharmaceuticals Inc. Symlin with metreleptin (pramlintide/metreleptin) for obesity. Began a Phase IIb study (5/6/08); 

Phase II data showed patients experienced significantly more weight loss on average than those receiving placebo or either agent 

alone (7/9/09) 

Arena Pharmaceuticals Inc. Lorcaserin (lorcaserin hydrochloride) for obesity. Phase IIb data showed that patients experienced statistically 

significant greater weight loss, compared to placebo (12/8/08); Phase III met all three of its co-primary endpoints (3/30/09); 

Phase III data showed that 47.2% of treated patients achieved at least a 5% reduction in baseline weight at 52 weeks, compared 

to 25% of those in the placebo arm (9/18/09); Patients on lorcaserin lost 31% of their excess weight compared to 12% in the 

placebo group (10/26/09); Phase III data showed highly significant improvements or favorable trends compared to placebo in multiple 

secondary endpoints (10/27/09) 

Athersys Inc. ATHX-105, orally administered, for obesity. Phase I data showed it was well absorbed and well tolerated up to high 

doses (2/28/08) 

Corcept Therapeutics Inc. CORT 108297, lead nonsteroidal cortisol receptor antagonist for disease states associated with excess 

production of cortisol (obesity, diabetes and hypertension). Results showed that the compound has good bioavailability with halflife 

that may be compatible with once-a-day oral dosing (5/1/08) 

Genaera Corp. MSI-1436 (trodusquemine), highly selective inhibitor of PTP1B for Type II diabetes and obesity. Phase I data showed 

it was well tolerated by overweight and obese volunteers (7/25/08); Phase Ib data demonstrated meaningful improvement in four 

primary outcomes used to evaluate Type II diabetes (2/10/09) 

Genfit SA GFT505, part of Genfit's selective nuclear receptor modulator platform, for prediabetic patients with atherogenic dyslipidemia 

and abdominal obesity. Phase II data showed it was well tolerated (11/23/09) 

Hollis-Eden Pharmaceuticals Inc. Triolex (HE3286) for obesity. Phase I/II data showed it was safe and well tolerated in obese 

insulin resistant subjects (9/25/08) 

Kythera Bio-pharmaceuticals Inc. ATX-101, an injectable drug for obesity. Phase II data showed that two of three dosing regimens 

yielded a statistically significant reduction of unwanted submental fat compared to placebo (10/2/09) 

MDRNA Inc. PYY(3-36) peptide, nasal spray treatment for obesity. Completed enrollment of 551 patients (1/8/08); Phase II data 

showed it was not effective as a single agent for weight loss (8/1/08) 

NeuroSearch AS Tesofensine, designed to inhibit the presynaptic uptake of the neurotransmitters noradrenaline, dopamine and 

serotonin, for obesity. Phase II data showed that its obesity compound produced a weight loss twice that of currently approved 

obesity drugs (10/23/08) 

Obecure Ltd. Histalean, comprised of betahistine, an H1 receptor agonist and partial H3 receptor antagonist, for obesity. Began a 

Phase II trial (9/8/08); Completed enrollment in a Phase IIb study (1/20/09) 

Obecure Ltd. Histalean in combination with olanzapine, to mitigate weight gain side effect associated with Zyprexa. Phase Ib data 

showed it was safe and indicated a statistically significant reduction in mean weight gain (6/15/09) 

Orexigen Therapeutics Inc. Contrave, a fixed-dose combination of sustained-release bupropion and Orexigen's sustained release 

naltrexone for obesity. Completed enrollment in NB-301, the second of four Phase III trials (4/22/08); Phase III data showed a significant 

reduction in body weight, meeting co-primary endpoints (1/9/09); Phase III data showed it met its endpoints in its three 

remaining pivotal studies (7/20/09); Phase III data demonstrated an excess body weight loss of 30% and 31.7% vs. placebo rates 

of 6.7% and 4.7% (10/26/09); Phase III data showed that about 25% to 33% of patients lost 10% or more of their body weight 

and 12% to 16% lost at least 15% (10/27/09) 

Orexigen Therapeutics Inc. Empatic, a fixed-dose combination of zonisamide sustained release and bupropion sustained release, 

for obesity. Phase IIb data showed weight loss through 48 weeks for those receiving 360 mg in the intent-to-treat group of 14% 

and 15.1% in the completer group (1/7/08); Began randomizing patients in ZB-202, a second Phase IIb trial (7/9/08); Phase IIb data 

showed it met its primary efficacy endpoint by demonstrating statistically significantly greater weight loss for both Empatic doses 

compared to monotherapies and placebo (9/30/09) 


124 

Obesity Deals and Data, cont. 

Orexigen Therapeutics Inc. OREX-003, a sustained-release formulation of zonisamide plus olanzapine, for drug-associated 

weight gain. Started a Phase IIa trial (10/2/08) 

OSI Pharmaceuticals Inc. PSN602, an oral dural monoamine reuptake inhibitor and 5-HTIA agonist, for obesity. Started the firstin-human 

study of PSN602 (6/19/08); Completed a Phase I trial (5/12/09) 

Pfizer Inc. CP-945,598, a selective antagonist of the cannabinoid type 1 receptor, for obesity. Pfizer terminated its Phase III development 

following conversations with the FDA and the failure of other similar obesity drugs (11/6/08) 

Sanofi-Aventis Group Acomplia (rimonabant) for obesity. Company is complying with an EMEA recommendation to suspend 

marketing due to potentially higher risks and lower efficacy than originally anticipated (10/23/08) 

Vivus Inc. Qnexa, a combination phentermine topiramate drug, for obesity. Started a six-month extension study (1/9/08); 

Completed enrollment in the 28-week EQUATE study with more than 700 patients (3/4); completed enrollment in the EQUIP study 

(3/27/08); Completed enrollment in the last of three Phase III studies in patients with comorbidities, including hypertension, dyslipidemia, 

or Type II diabetes (4/22/08); The first of three Phase III trials met its endpoint, demonstrating average weight loss of 9.2% 

at the full dose and 8.5% at the mid-dose, compared to 1.7% for the placebo group (12/11/08); Phase III data showed a significant 

control of blood sugar in nondiabetic subjects receiving Qnexa vs. placebo (1/12/09); Phase III data showed a higher weight 

loss in treated patients than in placebo (9/9/09); The drug's effect was consistent across all levels of body mass index in the EQUIP 

trial, and a measure of excess body weight loss was 42% in the intent-to-treat population of the CONQUER study (10/26/09) 

Source: BioWorld Insight. 


Total and Older Population, U.S.: 1950-2050 

number in millions 

450 

400 

350 

300 

250 

200 

150 

Total population 

100 

65 years and older 

75 years and older 

50 

65-74 years 

0 

1950 1960 1970 1980 1990 2000 2010* 2020* 2030* 2040* 2050* 

Year 

Note: *projected 

Source: U.S. Census Bureau.

1000 Genomes Project, 106-107 

11BHSD inhibitor, 39, 54 

2-AG, 105 

5-HT2b, 44 

5-HT2c, 37-38, 41-44 

5HT-6 antagonists, 39 

7 Health Ventures, 90 

7TM Pharma, 39, 54-55, 123 

A 

Abbott, 35, 38, 40, 47 

Abiliti, 87 

AC2307, 39 

Acomplia, 35, 38-40, 45, 54, 63, 105, 

124 

Actemra, 103 

Actical, 94 

ActiGraph, 94 

Actiheart, 94 

Actiware-PLM, 94 

Actiwatch, 94 

ActiWeb, 94 

Actos, 101 

Adipex-P, 35 

Adjustable Balloon System, 89 

adropin, 102-103 

Advanced Technology Ventures, 73, 

80 

Aegis Therapeutics, 55, 122 

Aestis, 96-97 

AEterna Zentaris, 39 

AEZS-123, 39 

Affinity Capital Partners, 82 

Afghanistan, 24 

Africa, 24, 27, 120-121 

Agios Pharmaceuticals, 55 

Aipermon, 96 

AiperMotion, 96 

AiperSunny, 96 

Aisling Capital, 83 

Albany Medical College, 55, 122 

Algeria, 24 

Alizyme, 39, 50-51, 61, 123 

Allergan, 67, 74-76, 78, 82, 88-89, 93 

Alli, 35, 38 

Alpco Diagnostics, 98 

Alzheimer’s disease, 20 

American, 20, 27, 29, 65, 67, 69-70, 

72, 74-75, 78, 91-93, 112 

American Diabetes Association, 43, 

50, 53-54, 58, 60, 70 

American Society of Metabolic and 

Bariatric Surgeons, 67, 69-71, 75, 84, 

89, 92-93 

Amylin, 35, 39, 51, 53, 122-123 

ANG2004, 39 

Angel’s Forum, 87 

Angiochem, 39 

Angola, 24, 26 

Anthill Technologies, 122 

appetite, 35, 40, 47, 60, 99-100, 104- 

105 

AR9281, 39, 53 

Arboretum Ventures, 82 

Arena Pharmaceuticals, 37-39, 41-46, 

48, 51, 61, 123 

Arete, 39, 53 

Argenta Discovery, 122 

Armenia, 24, 26 

Asia, 27, 121 

AstraZeneca, 39, 54-55, 59, 122-123 

Athersys, 61, 123 

ATHX-105, 61, 123 

ATL-962, 39, 50 

ATX-101, 123 

Australia, 25, 81, 85-86, 94, 96 

Austria, 25 

AZD4017, 39, 54 

AZD7687, 39, 54 

AZD8329, 39, 54 

Azerbaijan, 24 

Azimuth Opportunity, 42-43 

B 

bacTRAP, 58 

Bangladesh, 24, 26 

bariatric surgery, 13-14, 16-17, 19, 

66-78, 80-82, 85, 88, 91-94, 97 

BAROnova, 82, 89, 93 

Barosense, 71, 89-90, 93 

Barrett’s esophagus, 82 

BDNF, 104 

Beckman Coulter, 98 

Beijing Genomics Institute, 107 

Belgium, 25, 58 

Benin, 24, 26 

Beth Israel Deaconess Medical Center, 

92, 102 

Bhutan, 24 

Biocompatibles, 122 

Biomeasure, 102 

BioVista, 55 

Biovitrum, 55-56, 122 

blood pressure, 37, 44-47, 85-86 

blood sugar, 80, 97, 106 

BOD POD, 94 

body composition analyzer, 93-94 

body mass index, 14, 18, 20, 27-30, 

33, 37, 54, 68-69, 74-76, 79-80, 82, 

84-85, 94, 96, 99-101, 104, 107 

BodyMedia, 95 

Bodystat, 94 

Boehringer Ingelheim, 57, 122 

Bolivia, 24, 26 

Boston Scientific, 87 

INDEX 

Boston University School of Medicine, 

100 

Braasch Biotech, 56 

Bridge Bio-Research, 122 

Bristol-Myers Squibb, 35 

Brown University, 67 

Bruker Optics, 93 

bupropion, 35, 37-38, 40, 42, 45, 47- 

49, 52, 62 

Burkina Faso, 24 

Burundi, 24, 26 

Byetta, 35, 50-51 

C 

C.R. Bard, 71-72, 93 

C/EBP-beta, 102 

California Institute of Technology, 13 

Cambodia, 24, 26 

Cambridge Biotechnology, 56 

Cambridge University, 102 

Cameroon, 24, 26 

Canada, 25, 60, 75, 88, 90 

cancer, 13, 15, 20-22, 50, 55-56, 60, 

67, 69, 81, 99, 103, 111, 115, 118, 

122 

Cape Verde, 24 

CardioCoach VO2, 94 

cardiovascular, 41-42, 49-50, 54, 58, 

60, 75, 94-95, 100, 106-107, 111 

Case Control Consortium, 107 

Catalyst Health Ventures, 80 

CB Health Ventures, 87 

CB1, 40, 54-55, 61-63, 105 

CB2, 105 

Cedars-Sinai Medical Center, 76 

Cell Metabolism, 58, 100-102, 105 

Cell, 103, 106 

Center for Obesity Research and 

Education, 107 

Centers for Disease Control and 

Prevention, 18-21, 23, 29, 33, 36, 82 

Centers for Medicare & Medicaid 

Services, 67-68 

Central African Republic, 24, 26 

cetilistat, 39, 50-51, 123 

Chad, 24, 26 

Chicago Growth Partners, 73 

childhood obesity, 22-23, 112-113, 

116, 118 

Children’s Hospital Medical Center, 68 

cholesterol, 37, 44, 47, 53, 60-61, 

102, 105 

Cincinnati Children’s Hospital Medical 

Center, 69, 100 

City College of New York, 22 

Colby Pharmaceutical, 56 

Colombia, 24, 120 

Columbia University, 22, 75, 99 


126 

combination therapy, 37, 40, 42, 44, 

48-49, 51-53 

Compellis Pharmaceuticals, 56 

Congo, 24, 26 

Contrave, 37-40, 42, 44-50, 52, 62, 

123 

Corcept Therapeutics, 39, 56, 123 

CORT 108297, 39, 56, 123 

Cosmed, 93-94 

Côte D'Ivoire, 24 

Covidien Ventures, 82, 91, 93 

CP404, 56 

CP-945,598, 35, 38, 63, 124 

CPC-410, 56 

Creighton University School of 

Medicine, 83 

Cuba, 24 

Cutlass Capital, 80 

CV Therapeutics, 53 

CYP3A4, 62 

Czech Republic, 25, 90 

D 

Daelim Solar, 94 

Dana-Farber Cancer Institute, 102 

Davalintide, 39, 51, 53 

deCode Genetics, 104 

Deerfield Management, 42-43, 48 

Delphi Ventures, 90 

Denmark, 25, 50, 53-55, 60, 96 

DeNovo Ventures, 73 

depression, 18, 20, 35, 38, 40, 47-48, 

52, 62, 114, 118-119 

DeveloGen, 57, 122 

dexfenfluramine, 65 

DFJ ePlanet, 87 

diabesity, 75 

diabetes, 15-16, 20-22, 28, 30, 35, 

37, 41, 43, 45-47, 49-51, 53-62, 65, 

67-71, 74-75, 77-84, 86-87, 91-93, 

95, 99-103, 105-107, 110, 118-119, 

122-124 

Diagnostic Systems Laboratories, 98 

diet, 14-17, 23, 35, 38-40, 44-47, 49, 

53-54, 60, 62, 67, 69, 76, 79, 89-90, 

92-93, 96-98, 101-103, 105, 107 

diltiazem, 56 

Discovery series, 93 

Djibouti, 24, 26 

DNA, 104, 107 

Domain Associates, 80 

dopamine, 38, 40, 47-48, 52-53 

Dual Energy X-ray, 95 

duodenal switch, 74-75, 78 

dyslipidemia, 45, 53, 57 

E 

EasyBand, 75 


eBAT, 102 

Echo Medical Systems, 93 

EchoMRI, 93 

Ecuador, 24 

EDF Ventures, 82 

Egypt, 24, 120 

Eisai, 35 

El Salvador, 24 

Eli Lilly, 35, 51 

Elixir, 39, 57 

Emisphere, 39, 54 

Emory University, 33 

Empatic, 39-40, 48, 52-53, 62, 123 

EndoBarrier, 65, 78-80, 92 

Endocinch, 71-72 

EndoGastric Solutions, 73, 93 

Endosphere, 82, 92-93 

EndoVx, 83, 93 

EnteroMedics, 83-86, 92-93 

Envoy Therapeutics, 58 

Eritrea, 24, 26 

EsophyX, 73 

Esteve, 39 

Ethicon Endo-Surgery, 76, 91, 93 

Ethiopia, 24, 26 

Europe, 24, 27, 40, 63, 74-75, 78-80, 

85-88, 90, 105 

ExoTech Bio Solutions, 90 

F 

Fasgen, 57 

fatty acids, 99-101 

Fen-phen, 35, 38, 40, 45, 65, 103 

fibrinogen, 101 

Finland, 25 

Fitmate, 93-94 

Foundation Medical Partners, 73 

France, 25, 89, 97 

Frazier Healthcare Ventures, 90 

Fulfillium, 89-90, 93 

Full Sense, 88 

G 

Galapagos, 58-59, 122 

Galenea, 122 

Gambia, 25-26 

gastrectomy sleeve, 75, 78 

gastric banding, 19, 73-78, 87, 107 

gastric bypass, 19, 44, 65, 67, 70-79, 

84, 86-87, 92-93, 100 

Gastric Contractility Modulation, 87 

gastric sleeving, 74 

gastroesophageal reflux disorder, 72-73, 

77, 82-83, 88 

Gastrx, 92 

g-Cath, 72 

GE Healthcare, 93, 95 

Gelesis, 89-91 

Genaera, 61, 123 

gene therapy, 13, 23 

genetics, 20, 23, 29, 92, 98, 116 

Genfit, 39, 57-58, 123 

GENova Bio-therapeutics, 122 

Georgia, 24 

Germany, 25, 57, 74 

GFT505, 123 

Ghana, 24 

ghrelin, 39, 57, 91, 98 

GI Dynamics, 65, 78-80, 92-93 

Gilead Sciences, 53 

GlaxoSmithKline, 35, 38 

Glenmark, 39 

Glucagon, 50, 58, 60 

Glucophage, 35 

glucose, 40, 53-55, 58-61, 79, 82, 97, 

100-103, 105-106 

Glumetza, 35 

GPR119, 54 

g-Prox, 72, 81 

GRC 9332, 39 

Greece, 25 

Guatemala, 24, 26 

Guidant, 87 

Guinea, 24, 26 

H 

H3 receptor antagonist, 51, 54 

Haiti, 24, 26 

Halo Fund, 87 

Halsa Pharmaceuticals, 58, 123 

HapMap, 107 

Harvard Medical School, 102 

Harvard University, 90 

HbA1c, 37, 49 

Health and Human Services, 14-15, 19 

health care, 14-17, 19, 21-22, 28, 31, 

33, 35, 115, 117-119 

heart disease, 13, 16, 20-21, 28, 44- 

45, 56, 65, 68-69, 100, 102-104, 106, 

115, 118 

Heliogast, 89 

Helioscopie, 89 

Heliosite, 89 

Heliosphere, 89 

high blood pressure, 37, 47, 100, 105 

Highland Capital Partners, 82 

Histalean, 39, 51-52, 123 

HLM Venture Partners, 81 

Hollis-Eden Pharmaceuticals, 123 

Hologic, 93 

Honduras, 24, 26 

HPP404, 39, 54 

Hungary, 25 

hypertension, 15, 21-22, 28, 45, 53, 

57, 65, 69, 77, 84-86, 118-119, 123- 

124

I 

Iceland, 25 

ImpediMed, 94 

Implantable Pulse Generator, 84, 87 

Incisionless Operating Platform, 71-72, 

81 

India, 24, 26 

Indonesia, 24 

inflammation, 55, 8-60, 101-102, 

104-105, 107 

insulin, 53, 57, 60, 62, 100-103, 106 

INT-777, 39, 58 

Intarcia, 39 

Intercept, 39, 58 

Interleukin Genetics, 97-98 

International Federation for the Surgery 

of Obesity and Metabolic Disorders, 80 

Intersouth Partners, 83 

intragastric balloons, 88-90 

IntraPace, 84, 87 

Invesco Private Capital, 90 

Ionamin, 35 

Iran, 24 

Iraq, 24 

Ireland, 25 

ISIS 113715, 58 

Isis Pharmaceuticals, 58 

Israel, 51, 59, 88-91, 98, 120 

Italy, 25, 56, 76, 94 

ITCA 880, 39 

iWhisper, 96 

J 

Japan, 25, 39, 50-51, 53 

Jawon Medical, 94 

Johns Hopkins, 57 

Johnson & Johnson, 35, 47, 74, 76, 

80, 87 

Jordan, 24, 120 

Journal of Pediatrics, 100 

Journal of the American Medical 

Association, 107 

Juvederm, 75 

K 

Kaiser Permanente Ventures, 82 

Kenya, 24, 26, 120 

Kenz Lifecorder EX, 97 

Korea, 24-26, 94 

Korr Medical Technologies, 94 

Kythera Bio-pharmaceuticals, 123 

L 

L Capital Partners, 87 

Lansing Brown Investments, 91 

Laos, 24, 26 

laparoscopic, 19, 65, 67, 73, 75-77, 

83-85, 86-87, 91-92 

Lap-Band, 67, 70, 74-76, 78 

Laproscopic Adjustable Gastric Banding, 

77 

Latin America, 27, 121 

Latterell Venture Partners, 88 

Laval University, 98 

Leptin, 39, 51, 55-56, 99-101, 105 

Leptos Biomedical, 84, 87, 93 

Lesotho, 25 

LG Life Sciences, 39 

Liberia, 25-26 

Life Measurement, 94 

lifestyle medicine, 91 

lorcaserin, 37-39, 41-48, 61, 123 

Louisiana State University, 102 

Loyola University, 67 

Lumigan, 75 

Luxembourg, 25 

M 

Maastricht University, 97 

Madagascar, 25-26 

Maestro system, 83-86 

MAGL, 99 

Malawi, 25-26 

Mali, 25-26 

Marcadia Biotech, 58, 122 

Massachusetts General Hospital, 67, 

90 

Mauritania, 25 

MC-189, 94 

MCR-4, 39 

MDRNA, 61-62, 123 

Medeva Pharma, 35 

MedGem, 94 

Medicaid, 27, 33-34, 67, 74, 109 

Medicare, 19, 27, 33-34, 67-68, 74, 

109 

MEND Central, 96 

Merck, 35, 38-39, 58-59, 61-63, 104, 

122 

Meridia, 35, 38, 40, 47 

metabolic disease, 51, 54, 57-59 

metabolic syndrome, 50, 57, 60, 75, 

101, 104-105, 119, 122 

Metacure, 84, 87 

metreleptin, 39, 51, 53 

Mexico, 25, 120 

Microlife USA, 94 

Middle East, 27 

Mini Mitter, 94 

minimally invasive, 67, 72, 74, 76, 78, 

81-83, 87, 90-91 

Minispec, 93 

Monash University, 107 

Morgenthaler Ventures, 81 

MotionPod, 97 

Movea, 97 

Mozambique, 25-26 

MPI-0485520, 39, 59 

MPM Capital, 73 

MSI-1436, 61, 123 

Myanmar, 24 

Myriad, 39, 59 

N 

naltrexone, 37-40, 42, 45, 47-50, 52, 62 

Namibia, 25-26 

NAPEs, 103 

National Heart, Lung, and Blood 

Institute, 106 

National Human Genome Research 

Institute, 107 

National Institute of Child Health and 

Human Development, 104 

National Institute on Alcohol Abuse 

and Alcoholism, 105 

National Institutes of Health, 19, 23, 

29, 69, 88, 99, 104, 107 

National Research Council of Canada, 

122 

Nature, 102, 104 

Nature Chemical Biology, 58 

Nature Medicine, 101 

Nepal, 24, 26 

Netherlands, 25, 97 

neuroblocking, 83-84 

Neurogen, 62 

neuromodulation, 83-84, 87, 92-93 

NeuroSearch, 39, 53, 123 

NeuroSigma, 84, 88 

New England Journal of Medicine, 67, 

104 

NGD-4715, 62 

Nicaragua, 24, 26 

Niger, 25-26 

Nigeria, 120 

NitroMed, 44 

nObese, 81 

noradrenaline, 53 

norepinephrine, 54 

Norway, 25 

NOS, 73 

Novartis, 39, 60, 62 

Novartis Medical Nutrition, 97 

Novo Nordisk, 39, 50 

NOX-B11, 39 

Noxxon, 39 

O 

Oakwood Medical Investors, 73 

OBE102, 39, 59 

Obecure, 39, 51-52, 59, 123 

Obesity, 44 

Obesity Research, 34, 51, 53, 55, 60, 

63 


128 

Obesity Society, 21, 34-35, 41, 46, 48, 

50, 67, 93 

Obinepitide, 39, 54 

Ohio State University, 71, 73 

olanzapine, 51-52, 62 

Omniform, 74 

ONSET Ventures, 82 

Optifast, 97 

Orbera, 75, 88-89 

OrbiMed Advisors, 90 

Oregon Health & Science University, 

61, 122 

OREX-003, 62, 124 

OREX-004, 62 

Orexigen Therapeutics, 37-40, 42, 44- 

53, 61-62, 123-124 

Organix, 122 

OSI Pharmaceuticals, 39, 54, 124 

Oxford Bioscience Partners, 87 

Oxford University, 22, 107 

Oxylane, 97 

P 

p53, 101-102 

Pakistan, 24, 26, 120 

Palastine, 26 

Palatin Technologies, 39, 59, 123 

Palestine, 24 

Pappas Ventures, 90 

Parish Capital Advisors, 83 

PE Consortium, 60, 122 

PEA POD, 94 

Pennsylvania State University, 103 

Peru, 24 

Pfizer, 35, 38-39, 61-63, 124 

pharmaceuticals, 13, 30-31, 65-67, 

79-80, 97 

PharmaNess Neurosciences, 56 

phentermine, 35, 37-42, 44-48, 65 

Philippines, 24, 26 

Phoenix Care, 97 

Phoenix Pharmaceuticals, 98 

Pierre Fabre, 57-58 

Pinnacle Ventures, 81 

Plexxikon, 39 

Polaris Venture Partners, 80 

POMC, 103-104 

Portugal, 25 

Power Medical Interventions, 91 

Ppm1l, 104-105 

PRDM16, 102 

Proximagen Neuroscience, 56 

PSN602, 39, 54, 124 

PSN821, 39, 54 

PTP-1B, 58 

PureTech Ventures, 90-91 

PYY, 39, 54, 60-61, 123 


Q 

Qnexa, 37-42, 44-48, 52, 124 

Quaker BioVentures, 83 

Quantomix, 98 

Queensland BioCapital Funds, 90 

R 

Ranexa, 53 

Realize Adjustable Gastric Band, 76 

Reductil, 35 

ReeVue, 94 

Ren Pharmaceuticals, 49 

ReShape Balloon, 90 

ReShape Medical, 89-90 

Respironics, 94 

Restasis, 75 

revision surgery, 70-71 

RNAi, 13, 55, 59, 62 

Robert Wood Johnson Medical School, 

68 

Roche, 35, 38, 40, 47, 51, 62 

ROCK2, 54-55 

ROSE, 72 

Rosetta Inpharmatics, 104 

Roux-en-Y, 44, 67, 71, 73, 75, 77-78, 

100 

Rwanda, 25-26 

RWI Ventures, 90 

RXi Pharmaceuticals, 59 

S 

S-2367, 39, 53 

Sable Systems, 94 

Safestitch, 71, 82-83, 93 

Sanofi-Aventis, 35, 38-40, 45, 54, 61, 

63, 105, 124 

São Tomé, 25 

Sapient Capital, 82 

Satiety, 71, 80-81, 93 

SCD1, 39, 60 

Science, 103 

Scripps Research Institute, 99-100 

Seahorse Bioscience, 95 

Senegal, 25 

SenseWear, 95 

Sentinel Group, 88 

serotonin, 37-38, 40-44, 52-54, 99- 

100, 103-104 

Shionogi, 39, 53 

Sierra Leone, 25-26 

Silhouette Medical, 81, 92 

Sirona Biochem, 59, 122 

Skyline Ventures, 81 

sleep apnea, 21, 45-46, 68-69, 77 

sleeve gastrectomy, 70, 91 

Slovakia, 25 

SLx-2119, 39, 54 

SLx-4090, 39, 53 

SmartMotion, 97 

Society of American Gastroenterological 

and Endoscopic Surgeons, 72 

Society of Laparoendoscopic Surgeons, 

83 

SOCS3, 103 

soda, 13, 17, 116 

Somalia, 25 

somatostatin, 56 

South Africa, 120 

South America, 75, 78-79, 88 

Southwestern Medical Center, 75, 77 

space-fillers, 71, 88-90 

Spain, 25 

Spatz, 89-90 

Spider System, 83 

Spray Venture Partners, 88 

Sri Lanka, 24, 26 

StimPulse, 88 

Stomaphyx, 71, 73 

Sudan, 25-26, 120 

Superior Metabolic Intelligence, 94 

Surface Logix, 39, 53-54 

Suzuken, 97 

SV Life Sciences, 82-83 

Swaziland, 25-26 

Sweden, 25, 55 

Switzerland, 25, 60, 74, 82 

Symlin, 35, 39, 123 

Synecor LLC, 83 

Synergy Life Science Partners, 83, 90 

Syria, 24 

systems biology, 104-105 

T 

Tajikistan, 24, 26 

Takeda, 39, 50-51, 53, 101, 122-123 

Tanita, 94 

Tantalus, 84, 87 

Tanzania, 25-26 

taranabant, 35, 38, 62 

Targacept, 39 

TD-NMR spectrometers, 93 

Technology Partners, 88 

Tenuate, 35 

TERIS, 71, 89-90 

Tesofensine, 39, 53, 123 

TGap Ventures, 82 

TGFTX2, 39, 57 

Thomas, McNerney and Partners, 88 

Three Arch Partners, 81 

Timor-Leste, 24 

TM30338, 54 

TM30339, 39, 54, 123 

TM38837, 39, 55 

TOGA, 71, 80-81 

Togo, 25-26 

Topamax, 35

topiramate, 35, 37-42, 44-48 

Toucan Capital, 87 

TransEnterix, 83, 93 

Transition Therapeutics, 60 

TransPort, 72 

TransPyloric Shuttle, 82 

TransTech, 39, 53-54 

Tranzyme, 39 

Triolex, 123 

trodusquemine, 123 

TTP435, 39, 53 

Tulip Medical, 89-90 

Turkey, 25 

Type I diabetes, 57, 107 

Type II diabetes, 15, 20-21, 30, 37, 41, 

45-47, 49-50, 53-55, 57-62, 65, 68- 

70, 74-75, 78-82, 84, 87, 92, 101- 

103, 106-107, 110, 118-119, 122- 

124 

TZP-301, 39 

U 

U.S., 14-15, 17-20, 23, 25, 27-29, 33, 

35-40, 42, 45, 51, 58, 63, 65, 67-70, 

73-78, 80-82, 85-92, 96, 109, 112, 

115-116, 118-120, 122, 124 

Uganda, 25-26 

UGL269, 60 

UGP281, 39, 60 

UK, 20, 25, 50, 55, 63, 75, 94 

Unigene, 39, 60 

University of Alabama, 102 

University of California, 88, 101 

University of Cincinnati, 90, 103 

University of Colorado, 90 

University of Massachusetts, 103 

University of Missouri, 92 

University of Pittsburgh, 73 

University of Texas, 77 

University of Utah, 67 

USGI Medical, 71-72, 81, 93 

V 

V24343, 63 

vaccine, 56 

ValenTx, 82, 92-93 

Vbloc, 83-86, 92-93 

Velneperit, 39, 53 

Venrock, 81 

Ventana Biotech, 60, 122 

Vernalis, 63 

Victoza, 39, 50 

Vitae, 39 

Vivus, 37-42, 44-48, 51-52, 61, 124 

Vulcan Capital, 87 

W 

WAGR syndrome, 104 

WB-3000, 94 

Weight Control and Diabetes Research 

Center, 67 

weight gain, 40, 51, 53-54, 56, 62, 98 

weight loss, 13, 15-17, 30, 35, 37-42, 

44-50, 52-55, 57-61, 63, 65, 67-86, 

88-89, 91-98, 100, 103, 107 

Wellcome Trust Sanger Institute, 107 

Wharton Ventures, 90 

World Health Organization, 19-20, 22- 

23, 29, 82, 110-111, 121 

world hunger, 19, 23, 27, 120 

Wyeth, 35, 38-39, 45, 65 

X 

Xenical, 35, 38, 40, 47, 51 

Xenon, 39, 60 

XOMA, 39, 60 

XOMA 052, 39, 60 

Y 

Y2 receptor, 54 

Y4 receptor, 54 

Yale University, 103 

Yemen, 24, 26 

Z 

Zafgen, 39, 55, 122 

ZAG, 58 

Zambia, 25-26 

Zealand Pharma, 39, 60 

ZenBio, 60, 95 

ZGN-433, 39, 55 

Zimbabwe, 25-26 

Znomics, 61, 122 

Zonegran, 35 

zonisamide, 35, 40, 48, 52, 62 

ZP2929, 39, 60 

Zyban, 35 

Zyprexa, 51 


130

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