The evidence for the serious complications of obesity continues to grow. Recent research published in the New England Journal of Medicine by Lauby-Secretan and colleagues has linked excessive weight gain to eight more cancers bringing the total to thirteen malignancies for which obese patients are at increased risk. This adds to the already high burden of disease linked to obesity including type 2 diabetes and CV disorders, not to mention the increasing impact on health care costs owing to the need for specialist hospital beds and operating equipment, for example.

Awareness of obesity as a public health issue is high. However, treatment options remain limited. Diet and exercise can be effective but rarely on a sustained basis. The efficacy of metabolic and bariatric surgery is compelling but it is reserved mainly for the severely obese. There are medications available but they are generally considered to have suboptimal risk-benefit profiles and/or be too expensive. Moreover, the trend for targeting niche disorders that has grown in drug development now appears to be taking hold in those companies focussed on the obesity space.

Zafgen’s now discontinued beloranib was being developed for patients with Prader Willi Syndrome and severely obese diabetic patients. Rhythm Pharmaceuticals’ setmelanotide (RM-493), a melanocortin-4 receptor agonist, has been on the radar for some time now as a potential new medical therapy for obesity. But the company also appears to be targeting niche populations, and with dramatic success. In a paper by Kühnen and colleagues, also published in the NEJM, setmelanotide was administered to patients with proopiomelanocortin deficiency, a disorder documented in only 50 patients worldwide, which leads to unrelenting hyperphagia and as a result, severe obesity. Treatment with setmelanotide was associated with weight loss in excess of 50kg after 42 weeks in one patient and more than 20 kg after 12 weeks in another. This staggering degree of efficacy is closer to that from metabolic surgery than that of the currently available medications.

It remains to be seen if setmelanotide would be effective for general obesity. Moreover, people with such niche disorders are in urgent need of effective therapies. However, the whole healthcare system is at risk from the obesity juggernaut smashing healthcare budgets if efforts are not made to increase access to surgery or safe and efficacious pharmacotherapies. Developmental agents targeting niche populations can make commercial sense: despite smaller eligible patient populations, less safety evidence is required owing to the high unmet need, making the path to market faster resulting in longer time to maximize revenues generated from high priced products. While this may lead to fat profits, are we missing an opportunity for controlling the obesity epidemic? Food for thought…

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