Amylin Pharmaceuticals Announces Positive Results from Dose-Ranging Clinical Study of Pramlintide/Metreleptin Combination Treatm

Amylin Pharmaceuticals Announces Positive Results from Dose-Ranging Clinical Study of Pramlintide/Metreleptin Combination Treatment for Obesity

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 program.

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 nature.

"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."

Study Details

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 protocol deviations).

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 peer-reviewed journal.

About Obesity

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 obesity treatments.

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

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

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.