Imcivree Misses Primary Endpoints in Rare Obesity Trial

Rhythm Pharmaceuticals’s Phase III EMANATE trial evaluating Imcivree (setmelanotide) failed to meet its primary endpoints across four rare genetic obesity groups linked to the MC4R pathway.

The study assessed patients with heterozygous variants in POMC/PCSK1, LEPR, SRC1 (NCOA1), and SH2B1 genes. While modest reductions in body mass index (BMI) were observed, none reached statistical significance. High dropout rates further impacted outcomes.

Post hoc analyses showed more promising results in certain subgroups, but the company confirmed these findings will not be submitted to regulators, including the U.S. Food and Drug Administration.

Despite the setback, the drug maintained a consistent safety profile with known side effects such as nausea and injection site reactions. Rhythm plans to continue analyzing the data and shift focus toward next-generation MC4R therapies.

Imcivree remains approved for specific rare genetic obesity conditions, with further regulatory decisions pending in broader indications.

20-03-2026