Targeting Obesity: Win Some, Lose Some
Targeting obesity with new treatments presents remarkable challenges. For evidence of this harsh reality, look at the sharply contrasting news this week for two potential new drugs: beloranib and setmelanotide. All work on beloranib was canceled by its developer, Zafgen. Almost simultaneously, Rhythm Pharmaceuticals published breakthrough results in the New England Journal of Medicine (NEJM) with setmelanotide for a tiny group of patients.
Beloranib, which inhibits an enzyme called METAP2, had shown considerable promise for treating two rare and sever forms of obesity: Prader-Willi syndrome and obesity caused by injury to the brain’s hypothalamus. The first big setback for beloranib came in October last year with a patient death in clinical trials due to a blood clot. A second death brought a halt to all clinical trials in December.
This week, Zafgen called it quits for beloranib, because the company could not work out a strategy for addressing the safety concerns. Instead, Zafgen will shift its resources to a newer, potentially safer drug with the same mechanisim of action. The company’s labors to bring a drug for severe obesity to market earn our respect for persistence and focus.
A happier story emerged for Rhythm Pharmaceuticals this week. NEJM published impressive results for its new activator of the melanocortin-4 receptor setmelanotide. Two patients with a rare condition, Proopiomelanocortin (POMC) Deficiency, experienced striking responses to treatment with the new drug. POMC deficiency causes extreme hunger and severe obesity at an early age. It is virtually impossible to treat with much success.
Setmelanotide produced a sustained reduction in hunger and significant weight loss in both patients. The study reports data for 12 weeks with one of the patients and 42 weeks with the other.
As the roller coaster ride for Zafgen illustrates, these exciting results with setmelanotide represent nothing more than a good start. But they do point to the promise of serously targeting obesity in the many different forms it takes.
Just as different forms and stages of cancer require different treatments, we are learning that different forms of obesity can be successfully treated with targeted therapies.
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July 22, 2016