IMCIVREE (setmelanotide)

July 8, 2026: Rhythm Pharmaceuticals, Inc. (NASDAQ: RYTM) announced that results from its pivotal Phase 3 TRANSCEND trial of setmelanotide (IMCIVREE; MC4R agonist) in acquired hypothalamic obesity (patients aged ≥4 years) were published in The New England Journal of Medicine.

TRANSCEND was a 52-week, randomized, double-blind, placebo-controlled global study (n=120; 2:1 setmelanotide:placebo). In the primary analysis cohort (first 120 patients reaching 52 weeks), setmelanotide showed a -19.8% placebo-adjusted difference in BMI reduction. The primary endpoint was met: mean BMI change at 52 weeks was -16.5% from baseline on setmelanotide (n=81) vs +3.3% on placebo (n=39) (p<0.0001). At 52 weeks, 80% of setmelanotide-treated patients achieved ≥5% BMI reduction, with clinically meaningful improvements in hunger reported. Safety was described as generally well tolerated with no new safety signals; discontinuations due to adverse events were comparable to placebo.

Regulatory status updates: FDA approved IMCIVREE in March 2026 for acquired hypothalamic obesity in adults and children ≥4 years; EMA CHMP recommended marketing authorization expansion in March 2026. Rhythm also stated a Japan regulatory submission is under review.