Setmelanotide, Rhythm Pharmaceuticals’ novel melanocortin 4 receptor (MC4R) agonist, has demonstrated weight loss in an open-label, phase 2 trial recently published in the New England Journal of Medicine. Of course, publishing in the NEJM is a big deal so this caught our attention right away. Two patients with rare defects in the pro-opiomelanocortin (POMC) gene experienced weight loss following investigator-initiated treatment with setmelanotide, which was steady and sustained at ~four lbs/week, and was achieved primarily by a reduction in body fat. Notably, both patients reported markedly reduced hunger, while resting energy expenditure did not change by a significant margin. As a reminder, the company previously received breakthrough therapy and orphan drug designations for setmelanotide, and management is targeting the drug toward rare genetic disorders that result in early-onset obesity, including POMC deficiency which, according to company estimates, affects between 100-500 people worldwide. We heard discussion of MC4R at the most recent European Obesity Summit, and these results fall in-line with what we know about the pathway and its role in homeostasis, appetite, and weight regulation. While this study is small (estimated enrollment of 10 patients), we’re glad to have an initial look at positive phase 2 data that supports setmelanotide’s indication for POMC deficiency obesity. The drug is also currently in a phase 2 trial for Prader-Willi syndrome, and the company expects to expand setmelanotide development soon for two other MC4 pathway disorders – LepR deficiency obesity and POMC heterozygous deficiency obesity. We’ll keep a close watch on broader implications for obesity.
-- by Payal Marathe, Sarah Odeh, and Kelly Close