Rhythm Pharmaceuticals Presents Data on MC4R Agonists Setmelanotide and Bivamelagon at ENDO 2025

- Presentations highlight clinically meaningful reductions in BMI in patients with acquired hypothalamic obesity –

- Full data from Phase 3 TRANSCEND study underscore potential efficacy of setmelanotide, including with prior use or concomitant use of GLP-1s -

BOSTON, July 12, 2025 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, today announced data from three new presentations on the Company’s clinical programs for acquired hypothalamic obesity at the Endocrine Society’s Annual Meeting (ENDO 2025) taking place July 12-15 in San Francisco, CA.

Acquired hypothalamic obesity is a rare but serious condition caused by damage to the hypothalamic region of the brain, which includes the melanocortin-4 receptor (MC4R) pathway. This damage, often from brain tumors or their treatment, leads to rapid weight gain, hyperphagia, and low energy expenditure. Presentations on Rhythm’s acquired hypothalamic obesity programs at ENDO 2025 include:

Efficacy and Safety of Once-Daily Oral Bivamelagon in Acquired Hypothalamic Obesity: Results from a Double-blind, Multicenter, Placebo-Controlled, Randomized Phase 2 TrialIn a poster presentation, Vidhu Thaker, M.D., Pediatric Endocrinology, Columbia University, New York City, presented data from the Phase 2 SIGNAL trial evaluating bivamelagon, a daily oral, highly selective MC4R agonist, in patients with acquired hypothalamic obesity. In the 14-week, double-blind, four-arm, placebo-controlled portion of the trial, bivamelagon achieved statistically significant and clinically meaningful reductions in body mass index (BMI), consistent with BMI reductions achieved with setmelanotide therapy in similar patient populations in past trials. Other highlights include:

• -9.3% BMI reduction from baseline in the 600mg cohort (n=8) (p-value= 0.0004);
• -7.7% BMI reduction from baseline in the 400mg cohort (n=7) (p-value= 0.0002);
• -2.7% BMI reduction from baseline in the 200mg cohort (n=6) (p-value= 0.0180); and
• BMI for patients in the placebo cohort (n=7) increased by 2.2% over 14 weeks.

“Patients with acquired hypothalamic obesity struggle with accelerated weight gain that profoundly affects their life. These data demonstrate bivamelagon's potential as a transformative therapeutic option for patients and validate the potential opportunity for MC4R targeted therapies, if approved, to become the standard of care for this patient community,” said Vidhu Thaker, M.D., Associate Professor, Pediatric Endocrinology and Molecular Genetics, Department of Pediatrics, Columbia University Irving Medical Center, New York City.

Efficacy and Safety of Setmelanotide in Acquired Hypothalamic Obesity: Results from a Double-Blind, Multicenter, Placebo-Controlled, Randomized Phase 3 TrialIn a live oral presentation, Susan Phillips, M.D., Pediatric Endocrinology, University of California San Diego/Rady Children’s Hospital, San Diego, presented data from Rhythm’s pivotal Phase 3 TRANSCEND trial evaluating setmelanotide, the largest randomized, placebo-controlled trial in acquired hypothalamic obesity to date. Highlights from the presentation include:

• -19.8% placebo-adjusted difference in BMI reduction (N=120);
• Statistically significant BMI reductions following setmelanotide treatment were consistently observed across subgroups stratified by age (