Rhythm Pharmaceuticals Announces Pivotal Phase 3 TRANSCEND Trial Meets Primary Endpoint with -19.8% Placebo-adjusted BMI Reduction in Patients (N=120) with Acquired Hypothalamic Obesity

Core Insights - Rhythm Pharmaceuticals announced positive topline results from the pivotal Phase 3 TRANSCEND trial for setmelanotide, showing a significant reduction in body mass index (BMI) in patients with acquired hypothalamic obesity compared to placebo [1][2][5] - The trial demonstrated a mean BMI reduction of -16.5% for setmelanotide versus +3.3% for placebo at 52 weeks, with a placebo-adjusted reduction of -19.2% in adults and -20.2% in patients younger than 18 years [1][4][5] - The company plans to submit a supplemental New Drug Application to the FDA and a Type II variation request to the European Medicines Agency in Q3 2025 [3][4][7] Trial Details - The Phase 3 TRANSCEND trial is the largest and longest placebo-controlled study for acquired hypothalamic obesity, enrolling 120 patients aged 4 years and older [2][9] - The trial was double-blinded and randomized with a 2:1 ratio for setmelanotide versus placebo, focusing on the mean percent change in BMI from baseline after 52 weeks [9] - Key secondary endpoints showed clinically meaningful improvements, with no new safety signals reported [2][5] Safety and Tolerability - Setmelanotide was generally well tolerated, with common treatment-emergent adverse events including nausea, vomiting, diarrhea, injection site reactions, skin hyperpigmentation, and headache [2][5][21] - No serious adverse events leading to study discontinuation were reported, aligning with the established safety profile of setmelanotide [2][5] Market Potential - Acquired hypothalamic obesity is a rare condition affecting an estimated 5,000 to 10,000 individuals in the U.S., with additional populations in Japan and the EU [10][11] - The urgency for effective treatments is highlighted by the limited success of current approaches for long-term weight loss in this patient population [2][10] Future Developments - Rhythm anticipates presenting full data from the TRANSCEND study at an upcoming medical meeting [7] - The company is also developing next-generation MC4R agonists, currently in Phase 1/2 clinical trials for acquired hypothalamic obesity [7]