Drugs in the Pipeline Analysis

Drugs in the Pipeline
Analysis: Rising cost per day of therapy and increasing utilization are almost equal drivers of drug trend and spend. Drugs in the pipeline
will significantly impact both these factors as higher cost drugs replace less expensive ones, and new therapies are created to meet
previously unmet needs. Utilization may be affected by new drugs, new indications, or as a result of increased public awareness of new
treatments for common conditions such as through direct to consumer advertising. Knowing the drugs in the New Drug Application (NDA)
pipeline and their potential impact on health, cost per day, and utilization is an important step in forecasting and managing drug trend.
The pharmaceutical industry has historically concentrated on drug development in therapeutic areas that have the greatest patient
populations and sales potential. However, the Industry is also developing more targeted therapies, and drugs used in orphan populations, i.e.
less than 200,000 patients affected. Approximately 80 percent of drug trend over the next three years is expected to be driven by drugs in the
following therapeutic areas: cardiovascular, central nervous system, endocrine/diabetes, musculoskeletal/rheumatology, respiratory/allergy
diseases and cancer therapies.
Listed below are drugs for which an NDA or Biologic License Application (BLA) submission is undergoing review. An “approvable”
designation means that certain conditions must be met before final approval is granted.
How to use the data: Plan sponsors and consultants should keep abreast of drugs in the pipeline to better forecast drug expenditures and
more proactively manage the benefit. When considering drugs in the pipeline, it is important to differentiate between drugs that could result
in significant incremental costs and utilization for a plan versus drugs that will simply be a more or less expensive replacement for existing
drugs. Informed plan sponsors will also be better prepared to proactively evaluate management options needed to control a potential
blockbuster drug before it reaches the market. The information provided in the table below will be updated regularly with information on
drugs that may soon be marketed (approvable) or those with a recent NDA/ BLA submission.
Source: FDC Pink Sheets; FDA Centers for Drug Evaluation and Research, FDA Center for Biological Evaluation and Research, What's in
the Pipeline, The NDA Pipeline and other sources.
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
1

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
lanreotide acetate
(Somatuline ®
Autogel ® )
Tercica/IPSEN
Injection
For the once
monthly treatment
of acromegaly
NDA submitted:
10/2006
Estimated
approval date:
8/2007
Somatuline Autogel is an injectable
sustained-release formulation of
lanreotide, a somatostatin analogue.
Somatuline was initially developed in
Europe for the treatment of acromegaly
and, in most European countries, is also
approved for the treatment of symptoms
associated with neuroendocrine tumors.
The Somatuline Autogel formulation
releases lanreotide over a period of at
least 28 days and up to 56 days. The
product is packaged in a pre-filled
syringe for ease of administration.
In acromegaly, Somatuline is used
primarily when circulating levels of
growth hormone remain high despite
surgery or radiotherapy, and through its
inhibitory effects, Somatuline lowers
growth hormone and IGF-1 levels, thus
controlling disease progression and
relieving the symptoms associated with
active disease. IPSEN submitted a NDA
for Somatuline Autogel injection 60, 90
and 120 mg to treat patients with
acromegaly in October 2006.
Acromegaly is a
disorder caused
by the overproduction
of
growth hormone
secondary to a
benign tumor of
the anterior
pituitary gland.
Acromegaly
affects
approximately
15,000 people in
North America and
is most commonly
found in middleaged
adults.
Studies estimate
an all-cause
mortality rate
associated with
acromegaly of at
least twice the
normal population,
and a reduction in
life expectancy of
5 to 10 years.
NA
Similar to
Somavert
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
2

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
nilotinib
(Tasigna ® )
Novartis
Oral
Orphan drug
For the treatment
of patients with
resistance and/or
intolerance to
treatment with
Gleevec for
certain forms of
Philadelphia
chromosomepositive
(Ph+)
chronic myeloid
leukemia (CML)
NDA submitted:
11/2006
Estimated
approval date:
9/2007
Tasigna is a potent, orally
administered, aminopyrimidine tyrosine
kinase inhibitor. Nilotinib is a nextgeneration
therapy designed to inhibit
BCR-ABL, the result of Philadelphia
chromosome-positive CML
A study published in NEJM showed
Tasigna helped more than 90% of
patients diagnosed with unresponsive
Ph+ CML. Novartis also said it has rolled
out an expanded access program for
Tasigna. The global program, called
ENACT (Expanding Nilotinib Access in
Clinical Trials), will be available to
eligible patients in all phases of
Philadelphia chromosome-positive
chronic myeloid leukemia who are
resistant to or intolerant of treatment with
Novartis' Gleevec.
Tasigna appears to avoid the risk of
pleural effusions seen with iBristol-Myers
Squibb's Sprycel, according to Novartis.
Novartis will likely use safety as a
differentiator between the two agents.
CML is malignant
myeloproliferative
disorder in which
normal blood cell
production is
almost completely
replaced by
leukemia (myeloid)
cells. Bone
marrow
transplantation is
the only cure for
this disease but
age, health status
and ability to find a
suitable donor
precludes this
option for many
patients. Bcr- Abl
is recognized as
the key cause and
driver of the
proliferation of
white blood cells
that characterizes
Ph+ CML.
NA $130 - $150
per day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
3

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
olmesartan/
amlodipine
besylate
(Azor )
Daiichi
Oral
For the treatment
of hypertension
NDA submitted:
11/2006
Estimated
approval date:
9/2007
Daiichi Sankyo submitted an NDA for a
fixed-dose combination of its angiotensin
receptor blocker Benicar (olmesartan)
and the calcium channel blocker
amlodipine besylate (Norvasc). The
combination therapy may be used alone
or with other antihypertensive drugs.
The firm is targeting a launch of the
fixed-dose combination in fall 2007,
shortly after approval.
In a phase III trial of 1940 patients with
mild to severe hypertension, amlodipine
(5 mg – 10 mg)/olmesartan (10 mg – 40
mg) reduced seated systolic blood
pressure an average of 30.1mmHg and
seated diastolic blood pressure an
average of 19.0mmHg. This was in
comparison to mean reductions of
19.7mmHg and 12.7mmHg for systolic
and diastolic blood pressure,
respectively, in those patients treated
with amlodipine alone. Amlodipine/
olmesartan was well tolerated with a
similar adverse event profile to either
component alone.
According to
recent estimates,
nearly one in three
U.S. adults has
high blood
pressure, but
because there are
no symptoms,
nearly one-third of
these people don't
know they have it.
According to the
American Heart
Association, many
people have high
blood pressure for
years without
knowing it.
Uncontrolled high
blood pressure
can lead to stroke,
heart attack, heart
failure or kidney
failure. This is why
high blood
pressure is often
called the "silent
killer."
NA
$2 - $3 per
day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
4

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
nebivolol
(Nebilet ® )
Mylan/Forest
Oral
For the treatment
of hypertension
NDA submitted:
4/30/2004
Approvable:
6/1/2005
Estimated
approval date:
10/2007
Nebivolol is a once daily cardioselective
beta blocker (blocks beta-1 receptor)
currently being reviewed for the
treatment of hypertension. It also has
vasodilating properties due to
enhancement of endothelial nitric oxide
release.
Nebivolol has efficacy equivalent to or
better than that of atenolol, propranolol,
pindolol, and metoprolol. It has also
been associated with less adverse
effects than metoprolol. A multi-center,
double-blind study compared the
antihypertensive efficacy of nebivolol
and metoprolol in patients with mild to
moderate hypertension. Almost 80
percent of nebivolol and 65.6 percent of
metoprolol recipients achieved DBP ≤
90mm Hg. During the treatment phase
significantly more adverse events were
reported by metoprolol recipients.
Forest is also pursuing a CHF indication
for nebivolol. However, Forest has stated
that it intends to await the review for
hypertension before submitting the CHF
application.
According to
recent estimates,
nearly one in three
U.S. adults has
high blood
pressure, but
because there are
no symptoms,
nearly one-third of
these people don't
know they have it.
According to the
American Heart
Association, many
people have high
blood pressure for
years without
knowing it.
Uncontrolled high
blood pressure
can lead to stroke,
heart attack, heart
failure or kidney
failure. This is why
high blood
pressure is often
called the "silent
killer."
$300 million
for
hypertension
($700 million
for the
planned
indication for
CHF)
$2 - $4 per
day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
5

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
raltegravir
(Isentress )
Merck
Oral
Priority review
For the treatment
of HIV-1 infections
in treatmentexperienced
patients
NDA submitted:
4/2007
Estimated
approval date:
10/2007
Isentress belongs to a new class of
investigational antiretroviral therapy
(ART) agents called integrase inhibitors
that inhibit the insertion of the HIV viral
DNA into human DNA. Integrase is one
of three HIV enzymes - reverse
transcriptase, protease and integrase -
required by the virus to reproduce. The
proposed use of Isentress is in
combination with other antiretroviral
agents for the treatment of HIV-1
infection in treatment-experienced
patients with evidence of HIV-1
replication despite ongoing antiretroviral
therapy.
Results from two Phase III studies of
Isentress demonstrated significantly
greater antiretroviral activity when used
in combination with optimized
background therapy (OBT) versus
placebo plus OBT in treatmentexperienced
HIV-infected patients who
had failed antiretroviral therapies and
who had HIV virus resistant to at least
one drug in each of the three available
classes of oral ARTs.
An estimated 40
million people are
currently infected
worldwide, and it
is estimated that
more than four
million new
infections occur
worldwide
annually. AIDS is
one of the top
causes of
infectious diseaserelated
mortality
worldwide,
responsible for
approximately
three million
deaths each year.
NA
$20 - $30 per
day
Isentress is being studied in a twice daily
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
6

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
sevelamer
carbonate
(Renvela )
Genzyme
Oral
Control of serum
phosphorus in
patients with
chronic kidney
disease on
hemodialysis
NDA submitted:
12/2006
Estimated
approval date:
10/2007
regimen as a single tablet administered
without regard to food. Isentress does
not require boosting with ritonavir.
Isentress is also being investigated in
treatment-naïve patients with HIV.
Renvela is a follow-on product to
Renagel with the hope of once-daily
dosing. The proposed indication is the
same as for Renagel, control of serum
phosphorus in patients with chronic
kidney disease on hemodialysis.
Renvela would initially come in 800 mg
tablets (which would not necessarily
improve dosing), but the compound is
also being studied in powder. Initial
studies of the once daily powder showed
that it was not as effective as Renagel.
However, the powder will allow for
sprinkling Renvela on food.
According to prescribing information,
Renagel patients must take one to four
tablets three times daily with meals,
depending on serum phosphorus levels.
Renagel is dosed in 400 mg and 800 mg
tablets. According to Genzyme, patient
compliance has been an issue with
Renagel. Genzyme is also seeking to
expand the patient population for
According to
Genzyme, there
are over 300,000
patients with stage
5 chronic kidney
disease on dialysis
in the United
States. These
patients have
limited or no
kidney function
and depend on
dialysis, along with
dietary restrictions
and phosphate
binders to
minimize serum
phosphorus.
Hyperphosphatemia
and
the secondary
hyperparathyroidism
that results have
NA
$10 - $12 per
day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
7

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
ixabepilone
Bristol-Myers
Squibb
Route of
administration not
disclosed
Priority review
For the treatment
of metastatic or
locally advanced
breast cancer as
second line
therapy
NDA submitted:
4/2007
Estimated
approval date:
10/2007
Renvela by eventually pursuing an
indication for the drug in CKD patients
who have not progressed to dialysis.
Ixabepilone is a semisynthetic analog of
epothilone B. Ixabepilone has antineoplastic
mechanism of action similar
to the taxanes. FDA granted ixabepilone
a priority review.
The proposed indications for ixabepilone
are as a monotherapy to treat patients
with metastatic or locally advanced
breast cancer after failure of an
anthracycline, a taxane, and
capecitabine and in combination with
capecitabine to treat patients with
metastatic or locally advanced breast
cancer after failure of an anthracycline
and a taxane. Phase III results showed
that patients treated with ixabepilone in
combination with capecitabine,
experienced a statistically significant
improvement in progression-free
survival, the primary endpoint, compared
to patients treated with capecitabine
alone. The drug is also being studied
with Herceptin in patients who are
been shown to
significantly
increase patient
mortality and
morbidity.
The American
Cancer Society
estimates that
more than 180,000
new cases of
breast cancer will
be diagnosed in
the US this year,
and almost 41,000
people will die
from the disease.
Metastatic breast
cancer is the most
advanced form of
the disease in
which the cancer
has spread to
other organs in the
body. Unlike
cancer that has
remained
contained in the
breast and
surrounding lymph
NA $200 - $300
per day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
8

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
sapropterin
(Kuvan )
BioMarin
Oral
Priority review,
Orphan drug
For the treatment
of mild to
moderate
phenylketonuria
(PKU)
NDA submitted:
5/2007
Estimated
approval date:
11/2007
Her2neu positive.
The manufacturer is co-developing
response-predicting biomarkers with the
drug, but has not disclosed the identity of
those biomarkers of interest.
Kuvan is an investigational oral small
molecule therapeutic for the treatment of
primarily moderate to mild forms of PKU.
The active ingredient in Kuvan,
sapropterin hydrochloride, is the
synthetic form of 6R-BH4, a naturally
occurring enzyme cofactor. FDA has
granted a priority review.
Positive results were announced from
11-week multi-center double-blind,
placebo controlled, Phase III study of
Kuvan, in combination with diet, in 90
patients who were 4-12 years old with
blood Phe levels below 480 mmol/L. The
results show that all pre-specified
efficacy and safety endpoints of the
double-blind, placebo-controlled study
were met. Kuvan treatment caused a
significant increase in phenylalanine
tolerance as well as a reduction in blood
phenylalanine levels. Patients received
a one-week treatment of Kuvan at a
nodes, once the
cancer has spread
to other organs,
the disease cannot
be cured, but can
be treated.
PKU is a genetic
disorder affecting
at least 50,000
patients under the
age of 40
worldwide with
approximately half
having the
moderate to mild
form of the
disease. PKU is
caused by a
deficiency of the
enzyme,
phenylalanine
hydroxylase
(PAH). PAH is
required for the
metabolism of
Phe, an essential
amino acid found
in most proteincontaining
foods. If
$35 million to
$100 million
Possibly over
$100 per day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
9

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
rilonacept
(IL-1 Trap)
Regeneron
Injection
Priority review,
Orphan drug
Treatment of
CIAS1-Associated
Periodic
Syndrome (CAPS)
NDA submitted:
5/2007
Estimated
approval date:
11/2007
dose of 20 mg/kg/day (Part 1). Of the 89
patients who completed Part 1, 50
subjects demonstrated a blood Phe
reduction of at least 30%, and 45 were
randomized to Kuvan (20 mg/kg/day) or
placebo in a 3:1 ratio, and enrolled in the
10-week double-blind, placebocontrolled
portion of the study (Part 2).
For the first three weeks, patients
maintained their pre-existing restricted
diet with no supplementation of
phenylalanine. Thereafter, every other
week, specific amounts of phenylalanine
were added (or removed) to the
restricted diet of each patient according
to pre-defined blood phenylalanine
levels. The maximum amount of Phe that
could be added to a patient diet during
the study was 50 mg/kg/day.
IL-1 is a soluble protein secreted by
certain cells in the body, which acts as a
messenger to help regulate immune and
inflammatory responses by attaching to
cell-surface receptors on cells that
participate in the body's immune system.
In excess, it can be harmful and has
been linked to a variety of inflammatory
diseases. The IL-1 Trap is designed to
attach to and neutralize IL-1 in the blood
PAH is not present
in sufficient
quantities, Phe
accumulates to
abnormally high
levels in the blood
and brain resulting
in a variety of
complications,
including severe
mental retardation
and brain damage,
mental illness,
seizures and
tremors, and
cognitive
problems.
CAPS is a family
of rare
autoinflammatory
diseases,
including Familial
Cold Autoinflammatory
Syndrome (FCAS)
and Muckle Wells
Syndrome (MWS).
NA $100-$200
per day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
10

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
ropinirole
extended-release
(Requip ® XL 24-
hour)
GlaxoSmithKline/
Skye
Treatment of
Parkinson’s
disease
NDA submitted:
2/2007
Estimated
approval date:
12/2007
stream before it can attach to cellsurface
receptors and generate signals
that can trigger disease in body tissue.
Once attached to the Trap, IL-1 cannot
bind to the cell surface receptors and,
together with the Trap, is eliminated from
the body. The IL-1 Trap has a long
duration in the blood stream and can be
delivered by weekly injection.
The Phase 3 program of the IL-1 Trap
included two studies (Part A and Part B).
Both studies met their primary endpoints
(Part A: p less than 0.0001 and Part B: p
less than 0.001). The primary endpoint
of both studies was the change in
disease activity, which was measured
using a composite symptom score
composed of a daily evaluation of
fever/chills, rash, fatigue, joint pain, and
eye redness/pain.
Requip XL 24-hour is a prolonged
release formulation of ropinirole. It has
been designed to provide a steady rate
of absorption in the body to help reduce
blood plasma fluctuations over 24 hours.
The once-daily formulation significantly
reduced "off" time and improved mood in
patients with Parkinson's disease who
CAPS is caused
by mutations in the
CIAS1 gene and is
associated with
elevated levels of
IL-1. CAPS
patients suffer
from fever, rash,
chills, arthralgia,
myalgia, and
fatigue. There are
currently no
approved
therapies for
CAPS.
Parkinson's
disease is a
chronic,
progressive and
debilitating
neurological
condition that
impairs the body's
$200 million $3 - $4 per
day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
11

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
Oral
are suboptimally controlled with
levodopa (L-dopa).
In a phase III study, Requip XL 24-hour
(n = 201) was titrated upwards from 2
mg/day to a maximum dose of 24
mg/day over the course of 24 weeks. At
8 mg/day, and with each subsequent
dose increase, L-dopa dose reduction
was required. Patients who did not
experience improvements in symptoms
after two up-titrations of ropinirole could
have their L-dopa dose increased back
up to baseline levels. At week 24, the
reduction in mean awake "off" time was
significantly greater in the ropinirole
group compared with those in the
placebo group. The adjusted mean
change from baseline was -2.1 hours
and -0.3 hours in the treated and
placebo groups, respectively, leaving an
adjusted mean treatment difference of -
1.7 hours (P

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
continuous
erythropoiesis
receptor activator
(Mircera )
Roche
Injection
For the treatment
of anemia in
patients with
chronic kidney
disease, either on
dialysis or not on
dialysis
NDA submitted:
4/2006
Approvable:
5/2007
Estimated
approval date: 4Q
2007
Mircera (Continuous Erythropoietin
Receptor Activator, CERA) is under FDA
review for the treatment of anemia in
chronic kidney disease (CKD) patients.
Roche plans to differentiate Mircera
based on a potential dosing advantage
in chronic kidney disease. Mircera is
administered every four weeks, while
Epogen is dosed weekly and Aranesp is
approved for weekly or every 3 week
dosing.
Amgen believes that Roche's method of
manufacture infringes patents covering
their anemia treatment Epogen. In
November 2005, Amgen filed a patent
infringement lawsuit against Roche
seeking an injunction preventing the
manufacture or sale of recombinant
human erythropoietin, including
pegylated versions. Amgen's patent
infringement trial versus Roche has been
set for September 2007.
In December 2006, FDA extended its
review of Mircera by three months after
Roche submitted additional data for the
compound. The extra data was
submitted to "help give the FDA
Anemia is a
complication
associated with
CKD, from early
stage illness to
kidney failure
requiring dialysis.
Normally, when
the body senses a
decrease in
oxygen, more
erythropoietin is
created by the
kidneys which
stimulates the
production of
oxygen-carrying
red blood cells in
the bone marrow.
This raises the red
blood cell count.
When this natural
mechanism is
hindered (such as
in kidney disease),
it is necessary to
stimulate the
receptors in the
bone marrow to
$1 billion $40 - $50 per
day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
13

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
levofolinic acid,
LFA
(Iso-Vorin )
Spectrum
Injection
For use in the
treatment of
osteosarcoma in
conjunction with
methotrexate
NDA re-submitted:
7/2007
Estimated
approval date:
1/2008
additional clarity in key areas that the
FDA is monitoring with already available
anti-anemia agents." In May 2007,
Mircera received an approvable letter.
Roche declined to say what was
requested by the FDA, except that no
additional studies were requested.
Roche is anticipating approval after a
second Advisory Committee meets to
discuss the erythropoietin agents in the
renal setting this fall.
Iso-Vorin (levofolinic acid, LFA) is the
pure active isomer of calcium leucovorin,
a drug commonly used in tandem with 5-
fluorouracil (5FU). 5FU/leucovorin is
regarded as part of standard care in
multiple treatment settings.
An amendment to the NDA was filed in
July and provides manufacturing
information and six months stability data
on commercial batches, required by the
FDA to complete its review of Iso-Vorin.
The NDA already has more than 15
years of history at FDA. An NDA for both
oral and injectable formulations of
levofolinic acid was filed in December
1990. A July 1991 meeting of the
Oncologic Drugs Advisory Committee
produce red blood
cells through
exogenous
administration of
erythropoietin.
Osteosarcoma is
the most common
type of cancer that
starts in the bone.
The cells that form
this cancer
produce bone
matrix, such as
osteoblasts in
normal bone, but
the cancerous
tissue of
osteosarcoma is
not as strong as
normal bones.
According to the
National Cancer
$200 million $5 - $6 per
day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
14

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
desvenlafaxine
(Pristiq )
Wyeth
Oral
For the treatment
of depression and
menopausal
symptoms
NDA submitted:
12/22/05
(depression);
2Q 2006
(menopausal
symptoms)
voted 6-2 in favor of approval, based
upon clinical data demonstrating the
efficacy, safety and bioequivalency in
comparison to the racemic leucovorin
form. During a review of the NDA
application that was on file with the FDA,
the FDA raised questions surrounding
the chemistry manufacturing and control
section of the NDA. The amendment to
the NDA filed in July provides
manufacturing information and six
months stability data on commercial
batches, required by the FDA to
complete its review of ISO-Vorin.
Spectrum acquired North American
rights to Iso-Vorin in early 2006 from
privately held Targent.
Pristiq is a metabolite of venlafaxine and
is Wyeth’s follow-on product to its
antidepressant Effexor XR ® . Pristiq
inhibits serotonin and norepinephrine
uptake and has exhibited antidepressant
effects very similar to venlafaxine in
Society, there are
about 900 new
cases of
osteosarcoma
diagnosed in the
U.S. each year.
Osteosarcoma is
about 50 percent
more common in
males than in
females. Most
osteosarcomas
occur between the
ages of 10 and 30.
Teenagers are the
most commonly
affected age
group, but it can
occur at any age.
About 10% of all
osteosarcomas
occur in people
over the age of 60.
Depression is the
most prevalent
mental health
condition in the
US, affecting
approximately 19
$1 billion $4 - $6 per
day
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
15

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
Approvable:
1/22/07
(depression);
7/24/07
(menopausal
symptoms)
Estimated FDA
action date:
2/2008
(depression);
2009 (menopausal
symptoms)
studies. However, Pristiq may have a
better pharmacokinetic profile and a
lower potential for drug-drug interactions
than venlafaxine due to lack of
Cytochrome P450 2D6 metabolism.
Wyeth received an approvable letter
from the FDA for Pristiq as a treatment
for adult patients with major depressive
disorder. FDA approval for this
indication is subject to several
conditions, including several postmarketing
commitments, including
submission of long-term relapse
prevention, low dose and pediatric
studies and additional clarity around the
Company's product education plan for
physicians and patients. Wyeth plans to
submit a complete response letter in
August, setting up an estimated
February 2008 action date, assuming a
six-month review cycle.
FDA issued an approvable letter for the
menopausal symptom indication as well.
Wyeth will need to provide additional
data regarding the potential for serious
adverse cardiovascular and hepatic
effects associated with the use of Pristiq
million American
adults each year.
Studies indicate
that depressive
episodes occur
twice as frequently
in women as in
men.
According to the
North American
Menopause
Society, there are
approximately 40
million women in
the U.S. of
menopausal age.
As many as 93
percent of women
going through
menopause
experience
vasomotor
symptoms such as
hot flashes.
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
16

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
gepirone
extended-release
Kramer/
GlaxoSmithKline
Oral
For the treatment
of major
depressive
disorder
NDA re-submitted:
5/2007
Estimated
approval date:
3/2008
in this indication. FDA requested that
these data come from a randomized,
placebo-controlled clinical trial of at least
one year duration conducted in
postmenopausal women. The FDA also
made additional clinical and chemistry
requests. This requirement for an
additional one-year clinical study could
push FDA approval of this indication
back by several years.
Gepirone ER may be a first-in-class
5HT1a agonist for the treatment of
depression. Data suggests that
gepirone ER, which affects brain
serotonin by binding to serotonin 5HT1a
receptors, could treat depression with a
low risk for the sexual side effects that
are known to occur with current
therapies.
Depression is the
most prevalent
mental health
condition in the
US, affecting
approximately 19
million American
adults each year.
$700 million $3 - $5 per
day
In May 2007, Fabre-Kramer submitted
an NDA amendment to the FDA for
gepirone extended-release for the
treatment of major depressive disorder.
The amendment responds to the FDA's
June 2004 request for an additional
positive short term efficacy trial for
gepirone ER.
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
17

Generic Drug
Name (Brand)
Drug Company
Route Indication(s) Regulatory
Priority review * Status
Therapeutic Considerations
Affected
Population
Estimated
Peak Sales
Estimated
Cost/day
The regulatory road for gepirone ER has
been a long one, stemming back to
2001, under the direction of several
different sponsors. FKP re-acquired
rights to gepirone ER from Akzo Nobel's
Organon in 2005. That action was taken
after the drug was determined twice by
FDA to be "not approvable." The drug
was originally submitted in 2001 and
deemed not approvable in April 2002
due to efficacy concerns. Organon
withdrew an NDA for the antidepressant
in 2004 after receiving a second not
approvable letter from FDA.
Abbreviations: NA = not available.
*Priority Review: an FDA designated status where the drug appears to represent an advance over available therapy. The FDA review time for these
drugs is usually shorter than other drugs (6 months compared to 10 months). 1P: priority review of a new molecular entity, 2P: priority review of a
chemical derived from a FDA approved drug, 3P: priority review of a new formulation of a FDA approved drug, 4P: priority review of a new combination
of FDA approved drugs.
Updated 8/2007
Copyright © 2007 Medco Health Solutions, Inc.
18