Rhythm Pharmaceuticals Presents Data on MC4R Agonists Setmelanotide and Bivamelagon at ENDO …

• Significant clinical data presented by Rhythm Pharmaceuticals (RYTM, Financial) on MC4R agonists for acquired hypothalamic obesity.
• Phase 3 TRANSCEND trial for setmelanotide achieved a 19.8% placebo-adjusted BMI reduction.
• Phase 2 SIGNAL trial for bivamelagon reported up to 9.3% BMI reduction in the highest dose cohort.

Rhythm Pharmaceuticals, Inc. (NASDAQ:RYTM) unveiled notable clinical data at the Endocrine Society’s Annual Meeting (ENDO 2025), showcasing the efficacy of their MC4R agonists, setmelanotide and bivamelagon, in treating acquired hypothalamic obesity—a rare condition resulting from brain damage affecting hunger and weight regulation.

The pivotal Phase 3 TRANSCEND trial, evaluating setmelanotide, demonstrated a remarkable 19.8% placebo-adjusted reduction in BMI across 120 patients. The trial highlighted consistent efficacy across age groups and genders. Importantly, patients who used setmelanotide alongside GLP-1 medications observed substantial benefits, with a 25.1% BMI reduction in those with prior and concomitant GLP-1 use compared to a 2.0% reduction in the placebo group.

In the Phase 2 SIGNAL trial, bivamelagon, a daily oral MC4R agonist, showed dose-dependent efficacy, achieving a significant 9.3% BMI reduction in the highest 600mg dose cohort. Conversely, patients in the placebo group experienced a 2.2% BMI increase over the same period. These findings underscore the potential of MC4R targeted therapies, if approved, to become the standard of care for patients with acquired hypothalamic obesity.

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