Amylin Pharmaceuticals, Inc. 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 per cent, significantly more than treatment with pramlintide alone (8.4 per cent; 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," said 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, 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."

The 24-week, phase IIA, randomised, 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 per cent of their body weight were eligible to continue the study. For the remaining 20 weeks, these subjects were randomised, 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.

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.

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, 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 per cent from baseline compared with a 1 per cent 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.