Findings Further Support Leptin as Part of Company's Integrated Neurohormonal
Therapy for Obesity (INTO) Strategy
SAN DIEGO, July 9 /PRNewswire-FirstCall/ -- Amylin Pharmaceuticals, Inc.
(Nasdaq: AMLN) today announced positive results from a 28-week dose-ranging
study of pramlintide/metreleptin, a combination treatment comprising
pramlintide, an analog of the natural hormone amylin, and metreleptin, an
analog of the natural hormone leptin, in overweight and obese patients. This
Phase 2 study successfully characterized patients who responded best to
treatment and also provided important information to inform dose selection.
At 28 weeks, evaluable patients with a starting body mass index (BMI) less
than 35 kg/m2 (n=149), and treated with the highest pramlintide/metreleptin
doses, experienced significantly more weight loss on average (11%; 22 pounds,
p<0.01) than those receiving placebo (1.8%; 4 pounds) or either agent alone
(approximately 5%; 10 pounds). Consistent with the physiologic role of leptin
in regulating body fat, the weight loss in these patients was predominantly
due to a reduction in fat mass (approximately 18 of the 22 pounds lost). These
study results confirm previous Phase 2 results with this combination therapy
and provide a solid foundation for the Company's ongoing obesity development
In the overall evaluable study population, all of the
pramlintide/metreleptin combination arms achieved more weight loss than
placebo. The magnitude of weight loss was found to be dependent on dosage and
baseline BMI. In a pre-specified analysis of evaluable patients with a
starting BMI less than 35 kg/m2, weight loss with pramlintide/metreleptin was
more than additive compared to that with pramlintide and metreleptin alone, a
finding that was not observed in the overall evaluable population.
"Despite their best efforts with diet and exercise alone, most overweight
or obese individuals experience progressive weight gain over time. To date,
the only highly effective treatment option is surgical and limited to the
minority of patients who have advanced to the most severe forms of obesity,"
said Steven R. Smith, M.D., professor and assistant director of clinical
research at the Pennington Biomedical Research Center. "Providing the over 80
million overweight and obese Americans who have a BMI less than 35 kg/m2 with
safe treatment options that offer compelling weight loss would be a
significant advancement in obesity drug development."
The combination therapy was well tolerated, and no cardiovascular or
neuropsychiatric (such as anxiety or depression) safety signals were observed.
Consistent with previous clinical experience, the most common side effects
seen with pramlintide/metreleptin combination treatment were injection site
adverse events and nausea, which were mostly mild or moderate and transient in
"These findings provide us with valuable data that will inform our
clinical and product development strategy moving forward," said Christian
Weyer, M.D., vice president, corporate development, diabetes and obesity at
Amylin Pharmaceuticals. "Our integrated neurohormonal approach to obesity
provides a broad research and development platform that has the potential to
yield transformational therapies that address a range of unmet patient needs
across the various classes of obesity."
This Phase 2, 28-week, double-blind, placebo-controlled multi-center study
randomized 608 obese or overweight patients with a BMI ranging from 27-45
kg/m2. Patients were well-distributed across this BMI range, with
approximately 40% of patients at a starting BMI less than 35 kg/m2. Following
a one-week placebo lead-in period, study subjects were randomized in a
balanced fashion to receive twice-daily therapy with one of the following
eight treatment regimens: 1) placebo/placebo; 2) pramlintide 360 mcg/placebo;
3) metreleptin 5 mg/placebo; 4) pramlintide 180 mcg/metreleptin 2.5 mg; 5)
pramlintide 180 mcg/metreleptin 5 mg; 6) pramlintide 360 mcg/metreleptin 1.25
mg; 7) pramlintide 360 mcg/metreleptin 2.5 mg; or 8) pramlintide 360
mcg/metreleptin 5 mg.
Lifestyle intervention was included throughout study (dietary, exercise
and behavioral). Body composition was assessed using DEXA scanning at
enrollment and again at study termination. Across all treatment arms,
approximately 60% (n=360) of patients were deemed evaluable (subjects who
completed at least 24 weeks of treatment on study medication and had no major
As part of an ongoing extension protocol, study participants may continue
on therapy for a total of 52 weeks. Data from this study will be submitted for
presentation at a future medical meeting and for publication in a
Obesity is a chronic disorder that affects millions of people and is
linked to increased health risk of several medical conditions including type 2
diabetes, non-alcoholic fatty liver disease, high blood pressure, heart
disease, stroke, osteoarthritis, sleep disorders and several types of cancers.
According to 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.
There are different classes of obesity defined by body mass index, or BMI.
Overweight is defined as BMI 25 to 29.9 kg/m2, Obesity Class I is BMI 30 to
34.9 kg/m2, Obesity Class II is BMI 35 to 39.9 kg/m2 and Obesity Class III is
BMI 40 kg/m2 or more. Of the over 100 million overweight and obese individuals
in the United States, over 80 million have a BMI less than 35 kg/m2. It is
estimated that approximately two-thirds of patients with type 2 diabetes are
overweight or obese, with a BMI less than 35 kg/m2. In addition, approximately
three-quarters of individuals with BMI less than 35 kg/m2 without type 2
diabetes have dyslipidemia and/or hypertension.
Amylin's Approach to Obesity Research and Development
Currently, physicians and patients seeking prescription medications for
weight loss have limited therapeutic options. New scientific advances have
established the key role of neurohormones in the physiological regulation of
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
About Pramlintide/Metreleptin Combination Treatment
Pramlintide acetate is a synthetic analog of the natural hormone 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.
To date, approximately 8,000 individuals have received pramlintide in clinical
trials, including more than 950 in obesity studies. 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. To date, more than 1,200
overweight or obese individuals have received metreleptin in clinical trials,
several of which were 16 weeks or longer in duration. In an initial 24-week,
Phase 2 clinical proof-of-concept study in 177 overweight or obese individuals
(baseline BMI 27-35 kg/m2), combination treatment with pramlintide/metreleptin
(360 mcg/5 mg twice daily) resulted in an average weight loss of 12.7% (25
pounds) from enrollment, significantly more than treatment with pramlintide
alone (360 mcg twice daily) who experienced an average weight loss of 8.4% (17
pounds) or metreleptin alone (5 mg twice daily) who experienced an average
weight loss of 8.2% (16 pounds).
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
headquartered in San Diego, California. 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 due to a number of risks and uncertainties,
including that our clinical trials may not start when planned and/or confirm
previous results; our preclinical studies may not be predictive; our product
candidates may not receive regulatory approval; and inherent scientific,
regulatory and other risks in the drug development and commercialization
process. These and additional risks and uncertainties are described more fully
in the Company's most recently filed SEC documents, including its Form 10-Q.
Amylin undertakes no duty to update these forward-looking statements.
SOURCE Amylin Pharmaceuticals, Inc.
/CONTACT: Anne Erickson of Amylin Pharmaceuticals, Inc., +1-858-754-4443,
Cell, +1-858-349-3195, firstname.lastname@example.org; or Rachel Martin of Edelman,
+1-323-202-1031, Cell, +1-323-373-5556, email@example.com, for Amylin
/Web Site: http://www.amylin.com /