Core Insights - Rhythm Pharmaceuticals presented new data on acquired hypothalamic obesity at the Endocrine Society's Annual Meeting (ENDO 2025), highlighting the efficacy of setmelanotide and bivamelagon in reducing body mass index (BMI) in affected patients [1][2][3] Group 1: Clinical Data and Efficacy - The Phase 3 TRANSCEND trial demonstrated significant BMI reductions with setmelanotide, showing a -9.3% reduction in the 600mg cohort, -7.7% in the 400mg cohort, and -2.7% in the 200mg cohort, while the placebo cohort experienced a 2.2% increase [4][5] - A placebo-adjusted difference of -19.8% in BMI reduction was observed across 120 participants, with significant reductions noted in various age and sex subgroups [5][6] - Bivamelagon, a daily oral MC4R agonist, also showed statistically significant BMI reductions in a Phase 2 trial, indicating its potential as a transformative treatment option for patients with acquired hypothalamic obesity [2][3] Group 2: Patient Population and Market Potential - Acquired hypothalamic obesity is a rare condition affecting an estimated 5,000 to 10,000 individuals in the U.S., with similar prevalence in Japan and the E.U. [11][10] - The condition is characterized by rapid weight gain and hyperphagia due to damage to the hypothalamic region of the brain, often following brain tumors or their treatment [10][11] - The presentations at ENDO 2025 underscore the potential for MC4R-targeted therapies to become the standard of care for this patient community if approved [2][3]

Core Insights - Rhythm Pharmaceuticals announced positive topline results from its Phase 2 trial of bivamelagon, showing significant BMI reductions in patients with acquired hypothalamic obesity [2][3] - The company plans to engage with regulatory authorities for a Phase 3 trial design and has requested an End-of-Phase 2 meeting with the U.S. FDA [7] Group 1: Trial Results - Bivamelagon achieved BMI reductions of -9.3% in the 600mg cohort and -7.7% in the 400mg cohort at 14 weeks [1][4] - A post-hoc analysis indicated that the BMI reductions from bivamelagon were consistent with those achieved by setmelanotide in similar patient populations [3][5] - Patients reported a mean reduction of -2.8 points in hunger scores in both the 600mg and 400mg cohorts [1][3] Group 2: Safety and Tolerability - The trial demonstrated safety and tolerability consistent with MC4R agonism, with limited instances of localized hyperpigmentation observed [4][6] - The most common adverse events included mild diarrhea and nausea, with one serious adverse event reported [6] Group 3: Next Steps and Regulatory Plans - Rhythm plans to seek input from U.S. and EU regulatory authorities regarding the Phase 3 trial design for bivamelagon [7] - The company is refining the formulation of bivamelagon to potentially improve tolerability before initiating the Phase 3 trial [7] Group 4: Company Background - Rhythm Pharmaceuticals is focused on transforming the lives of patients with rare neuroendocrine diseases and has in-licensed bivamelagon from LG Chem, Ltd [2][13] - The company’s lead asset, setmelanotide, is already approved for treating certain types of obesity [13][14]