Amylin Pharmaceuticals Inc. (AMLN)

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Amylin Pharmaceuticals Initiates Phase 2B Dose-Ranging Clinical Study of Pramlintide/Metreleptin Combination Treatment in Obesity
Monday May 5, 5:00 pm ET
Preclinical findings of amylin/leptin synergy and translational Phase 2A clinical results published online today in Proceedings of the National Academy of Sciences of the United States of America

SAN DIEGO, May 5 /PRNewswire-FirstCall/ -- Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN - News) today announced the initiation of a Phase 2B clinical study evaluating various dosing combinations of pramlintide, an analog of the natural hormone amylin, and recombinant human leptin (r-metHuLeptin; metreleptin) for the treatment of obesity. The objective of this dose-ranging study is to support dose selection for Phase 3, and to inform the ongoing development of a convenient delivery system for this combination regimen. The six-month, randomized, double-blind, placebo-controlled multi-center study will enroll approximately 600 overweight and obese subjects and is expected to complete in mid-2009.

"There is a tremendous medical need and market demand for a weight loss product that meets both safety and efficacy expectations of patients and physicians, and we believe that our integrated neurohormonal approach to obesity holds great promise for achieving this profile," stated Christian Weyer, M.D., Vice President of Clinical Research, Amylin Pharmaceuticals. "Building upon the positive results of our translational research program published today in PNAS, and the extensive clinical experience with both pramlintide and metreleptin as monotherapies, the newly initiated Phase 2B study will bring us one step closer to our goal of offering obese individuals a safe and effective therapy that results in meaningful weight loss."

The Phase 2B study will include a broad range of overweight and obese subjects (body mass index 27 to 45 kg/m2) and will compare various pramlintide/metreleptin combination regimens with each compound alone and with placebo.

PNAS Publication

Also today, comprehensive preclinical findings of amylin/leptin synergy, along with positive results of a translational Phase 2A clinical study were published online in PNAS, Proceedings of the National Academy of Sciences of the United States of America, in a scientific paper entitled, "Leptin Responsiveness Restored by Amylin Agonism in Diet-Induced Obesity: Evidence from Non-Clinical and Clinical Studies."

"Leptin is a fundamentally important hormone in energy metabolism with a unique role in inducing fat-specific weight loss and in preventing weight loss counterregulation," remarked Steven Smith, M.D., Professor and Assistant Associate Director of Clinical Research, Endocrinology Laboratory at the Pennington Biomedical Research Center. "The intriguing and important findings published today constitute a strong scientific basis for the development of peptide hormone combinations, and provide renewed hope of harnessing the therapeutic potential of leptin as part of an integrated neurohormonal approach to obesity pharmacotherapy."

The scientific studies included in the PNAS publication provide preclinical and clinical evidence that leptin responsiveness is at least partially restored by amylin agonism. In several independent experiments in diet-induced obese rats, co-administration of amylin, together with leptin, resulted in synergistic reductions in food intake (up to 45%) and body weight (up to 15%), effects considerably greater than with leptin or amylin treatment alone. Importantly, weight loss with amylin/leptin treatment was fat-specific, and not accompanied by a reduction in lean mass. Neurohistological studies provided important insights into the neurobiological basis of amylin/leptin synergy. Finally, the translational clinical research confirmed that findings in the non-clinical experiments are relevant to human obesity and suggest that metreleptin may be an effective partner to pramlintide in the treatment of obesity.

The full paper, published in the May 5, 2008 early edition of PNAS, is available online at http://www.pnas.org/. PNAS is one of the world's most prestigious multidisciplinary scientific journals.