FDA accepts Rhythm’s sNDA for setmelanotide in acquired hypothalamic obesity

The FDA has accepted for filing the Rhythm Pharmaceuticals’s supplemental New Drug Application (sNDA) for setmelanotide seeking approval for the treatment of conditions associated with acquired hypothalamic obesity.

Additionally, the European Medicines Agency (EMA) has confirmed validation of the Type II variation submission to the Marketing Authorization Application (MAA) for setmelanotide for the same indication. The application review began on 16 August by the Committee for Medicinal Products for Human Use (CHMP), which will issue an opinion to the European Commission (EC) regarding potential approval.

Setmelanotide is a melanocortin-4 receptor (MC4R) agonist, previously approved as IMCIVREE® by the FDA, the EMA, and UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) for obesity due to Bardet-Biedl syndrome and POMC, PCSK1 or LEPR deficiencies.

The sNDA and Type II Variation are supported by statistically significant and clinically meaningful data from the pivotal Phase 3 TRANSCEND trial of setmelanotide in 120 patients with acquired hypothalamic obesity. Topline results from TRANSCEND, the largest and longest randomized, placebo-controlled trial in acquired hypothalamic obesity to date. The global study met its primary endpoint, with a statistically significant -19.8% placebo-adjusted reduction in body mass index (BMI). For the primary endpoint of mean BMI change from baseline, study participants on setmelanotide therapy (n=81) achieved a -16.5% reduction compared with a +3.3% increase among patients on placebo (n=39) at 52 weeks (p<0.0001). Adult patients (age 18 and older; n=49) achieved a -19.2% placebo-adjusted BMI reduction at 52 weeks, and pediatric patients (younger than age 18; n=71) achieved a -20.2% placebo-adjusted BMI reduction at 52 weeks. Setmelanotide was generally well tolerated in the TRANSCEND study. The most common treatment-emergent adverse events (affecting >20% of participants) were nausea, vomiting, diarrhea, injection site reaction, skin hyperpigmentation and headache.