Findings validate novel integrated neurohormonal treatment of obesity
(INTO) strategy
SAN DIEGO, Nov. 15 /PRNewswire-FirstCall/ -- Amylin Pharmaceuticals,
Inc. (Nasdaq: AMLN) today announced positive results from a 24-week
proof-of-concept study with pramlintide, an analog of human amylin, and
recombinant human leptin (r-metHuLeptin; metreleptin) combination treatment
in overweight or obese subjects. At study end, pramlintide/metreleptin
treatment reduced body weight on average by 12.7 percent, significantly
more than treatment with pramlintide alone (8.4 percent; p<0.001). Subjects
treated with pramlintide/metreleptin lost an average of 25 pounds from
study start compared with an average of 17 pounds for subjects treated with
pramlintide alone. Subjects receiving pramlintide/metreleptin had
continuous weight loss through the end of the study compared to those
treated with pramlintide alone, whose weight loss had stabilized towards
the end of the study. At study start, the average weight of study
participants was approximately 205 pounds.
Consistent with previous clinical experience with pramlintide and
metreleptin as single agents, the most common side effects seen with
pramlintide/metreleptin combination treatment were injection site adverse
events and nausea, which were mostly mild to moderate and transient in
nature.
"We believe these important results provide convincing clinical
proof-of-concept, highlighting the tremendous potential of our integrated
neurohormonal strategy as a unique, innovative approach to obesity
pharmacotherapy," stated Alain D. Baron, M.D., Senior Vice President
Research, Amylin Pharmaceuticals. "The findings are consistent with our
internal discovery that amylin restores leptin responsiveness in
diet-induced obese rats, and thus greatly increase our confidence in the
predictive value of our preclinical obesity models. We now look forward to
advancing the pramlintide/metreleptin clinical program to the next stages
of development."
"The discovery of leptin in 1994 was a major scientific breakthrough
that revolutionized our understanding of the neurohormonal basis of
obesity," remarked Eric Ravussin, PhD, Professor, Pennington Biomedical
Research Center in Baton Rouge, Louisiana, and Immediate Past-President of
NAASO, The Obesity Society. "Leptin is a fundamentally important hormone in
the regulation of energy homeostasis, fat metabolism, glucose metabolism,
and body weight. These exciting clinical results provide renewed hope of
harnessing the therapeutic potential of leptin in the search for novel,
safe and more efficacious treatments for obesity."
Study Details
This 24-week, Phase 2A, randomized, double-blind,
active-drug-controlled, multicenter study enrolled 177 overweight and obese
subjects with a body mass index ranging from 27 to 35 kg/m2. For the
initial 4 weeks, all subjects received dietary instruction and treatment
with pramlintide (180 micrograms twice daily for two weeks, followed by 360
micrograms twice daily for two weeks). Subjects who completed the 4-week
lead-in period and who lost 2 to 8 percent of their body weight were
eligible to continue the study (n=139). For the remaining 20 weeks, these
subjects were randomized, in a 2:2:1 ratio to one of three groups, with
twice daily injection treatment of: 1) pramlintide 360
micrograms/metreleptin 5 milligrams; 2) pramlintide 360 micrograms/placebo;
or 3) metreleptin 5 milligrams/placebo.
Further study details will be presented at Amylin Pharmaceuticals'
Research and Development Day on November 28, 2007 and in future scientific
publications.
About Obesity
Obesity is a chronic condition that affects millions of people and is
linked to increased health risk of several medical conditions including
type 2 diabetes, high blood pressure, heart disease, stroke,
osteoarthritis, sleep disorders and several types of cancers. According to
NAASO, The Obesity Society, obesity is the second leading cause of
preventable death in the United States. The total direct and indirect cost
attributed to overweight and obesity health issues exceeds $100 billion in
the United States each year. Obesity is also rapidly becoming a major
health problem in all industrialized nations and many developing countries.
Obesity is measured by body mass index, or BMI, a mathematical formula
using a person's height and weight. A person with a BMI between 25 and 29.9
is considered overweight. A person with a BMI of 30 or more is considered
obese, and a person with a BMI of 40 or more is considered severely obese.
Amylin's Unique Approach to Obesity Research and Development
Physicians and patients seeking prescription medications for weight
loss have limited therapeutic options. New scientific advances have
established the key role of neurohormones in regulating appetite and energy
balance, as well as the importance of studying the interaction among these
hormones (within the brain) to uncover their full therapeutic potential.
Amylin scientists discovered that combination treatment with neurohormones
such as amylin and leptin can produce additive and synergistic weight loss
in animal models. These findings formed the basis for Amylin's innovative
integrated neurohormonal approach to the development of obesity treatments.
About Pramlintide and Metreleptin
Pramlintide is a synthetic analog of amylin, a neurohormone secreted by
the pancreas that is known to play a role in the regulation of appetite,
food intake and postprandial glucose concentrations. Pramlintide is the
active ingredient in SYMLIN(R), which is indicated for use by patients with
type 1 and type 2 diabetes who use mealtime insulin. Since launch, over
80,000 patients have been exposed to SYMLIN. To date, more than 6,000
individuals have received pramlintide in clinical trials, including more
than 800 in obesity studies. In previous clinical studies, obese subjects
treated with pramlintide 360 micrograms twice daily for 1 year experienced
an average weight loss of approximately 8 percent from baseline compared
with a 1 percent weight loss in patients receiving placebo. The most common
side effect observed with pramlintide treatment in previous obesity studies
was mild, transient nausea.
Metreleptin (methionyl recombinant leptin; r-metHuLeptin) is an analog
of human leptin, a neurohormone secreted by fat cells that plays a
fundamental role in the regulation of energy metabolism and body weight.
Amylin acquired exclusive rights to the leptin molecular franchise and
clinical program in 2006. To date, more than 1,000 individuals have
received metreleptin in clinical trials, several hundred of which were
obese and treated for 16 weeks or more. In multiple previous human clinical
trials with metreleptin treatment alone, minimal weight loss was observed.
This observation is consistent with findings in diet-induced obese rats,
and suggests the presence of leptin resistance. In contrast, and consistent
with findings in ob/ob (leptin deficient) mice, long-term treatment with
metreleptin has been shown to elicit profound, fat-specific weight loss in
severely obese individuals who are rendered leptin deficient by rare
genetic mutations of the leptin gene. The most common side effect observed
with metreleptin treatment in previous obesity studies was injection site
adverse events.
About Amylin
Amylin Pharmaceuticals is a biopharmaceutical company committed to
improving lives through the discovery, development and commercialization of
innovative medicines. Amylin has developed and gained approval for two
first-in-class medicines for diabetes, SYMLIN(R) (pramlintide acetate)
injection and BYETTA(R) (exenatide) injection. Amylin's research and
development activities leverage the company's expertise in metabolism to
develop potential therapies to treat diabetes and obesity. Amylin is
located in San Diego, California with over 1,800 employees nationwide.
Further information on Amylin Pharmaceuticals is available at
http://www.amylin.com.
This press release contains forward-looking statements about Amylin,
which involve risks and uncertainties. The Company's actual results could
differ materially from those discussed herein due to a number of risks and
uncertainties, including risks that future clinical trials may not
replicate previous results; risks that our preclinical studies may not be
predictive; risks that the FDA may not approve the Company's NDAs or
product candidates; and other risks inherent in the drug development and
commercialization process. These and additional risks and uncertainties are
described more fully in the Company's recently filed Form 10-Q. Amylin
disclaims any obligation to update these forward-looking statements.
SOURCE Amylin Pharmaceuticals, Inc.
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Related links:
http://www.amylin.com
CONTACT:
Alice Bahner Izzo of Amylin Pharmaceuticals,
Inc., +1-858-642-7272, +1-858-232-9072, Alice.Izzo@amylin.com
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