bioworld - Medical Device Daily

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.
THE BIOWORLD AND MEDICAL DEVICE DAILY OBESITY REPORT
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