FDA expands IMCIVREE label to acquired hypothalamic obesity as EMANATE misses primary endpoints

The FDA approved, on March 19, 2026, an expanded indication for Rhythm Pharmaceuticals’ IMCIVREE, or setmelanotide, for acquired hypothalamic obesity in adults and pediatric patients aged 4 years and older.

The approval was supported by the Phase 3 TRANSCEND trial in 142 patients. Rhythm said the study met its primary endpoint, with a statistically significant 18.4% placebo-adjusted reduction in BMI at 52 weeks. Rhythm said it estimates about 10,000 people in the U.S. are living with acquired hypothalamic obesity.

The label expansion came three days after a setback in Rhythm’s broader obesity program. On March 16, the company reported that all four independent substudies in the Phase 3 EMANATE trial failed to meet their pre-specified primary endpoints. Those substudies evaluated setmelanotide in patients with obesity due to heterozygous variants in POMC/PCSK1, LEPR, SRC1 (NCOA1), and SH2B1.

The company said it plans to continue analyzing the EMANATE dataset and evaluate potential clinical development paths forward for SRC1 and POMC with its next-generation MC4R agonists bivamelagon and RM-718.

Sources: Rhythm Pharmaceuticals