Core Insights - Rhythm Pharmaceuticals has received acceptance for its supplemental New Drug Application (sNDA) for setmelanotide from the U.S. FDA, with a PDUFA goal date set for December 20, 2025, indicating a priority review status [1] - The European Medicines Agency (EMA) has also validated a Type II variation submission for setmelanotide for the treatment of acquired hypothalamic obesity, with the review process initiated on August 16, 2025 [2] - Setmelanotide is already approved for other obesity-related conditions and is a melanocortin-4 receptor (MC4R) agonist, highlighting its potential in treating rare neuroendocrine diseases [3] Company Developments - Rhythm Pharmaceuticals will host an event titled "Commercial Readiness for Acquired Hypothalamic Obesity" on September 24, 2025, to discuss U.S. launch plans and the urgent need for treatment in this patient population [5] - The company emphasizes its commitment to expediting the availability of setmelanotide for patients suffering from acquired hypothalamic obesity, which presents unique challenges compared to general obesity [4] Clinical Trial Insights - The pivotal Phase 3 TRANSCEND trial involved 120 patients and demonstrated a statistically significant -19.8% placebo-adjusted reduction in body mass index (BMI) after 52 weeks of treatment with setmelanotide [4] - In the TRANSCEND trial, participants on setmelanotide achieved a -16.5% reduction in mean BMI compared to a +3.3% increase in the placebo group, with significant results across both adult and pediatric populations [4] Market Potential - Rhythm estimates that there are between 5,000 to 10,000 individuals in the U.S. and 3,500 to 10,000 in the EU living with acquired hypothalamic obesity, indicating a targeted market for setmelanotide [10]

Core Insights - Rhythm Pharmaceuticals (RYTM) shares increased by 36.6% following the announcement of positive top-line data from a Phase II study of the oral melanocortin-4 receptor (MC4R) agonist, bivamelagon, for treating acquired hypothalamic obesity [1][7]. Company Overview - Rhythm Pharmaceuticals is focused on developing treatments for obesity-related conditions, specifically acquired hypothalamic obesity, which is characterized by rapid weight gain and uncontrollable hunger due to hypothalamic damage [2][4]. - The company also markets setmelanotide, another MC4R agonist, under the brand name Imcivree for chronic weight management in patients with specific genetic conditions [4]. Study Results - The Phase II study demonstrated that bivamelagon resulted in statistically significant reductions in body mass index (BMI) after 14 weeks of treatment, with reductions of 9.3%, 7.7%, and 2.7% for the 600mg, 400mg, and 200mg doses, respectively [3][8]. - In contrast, the placebo group experienced a BMI increase of 2.2% over the same period [8]. - Patients receiving bivamelagon also reported a mean decrease of over 2.8 points in peak hunger scores on a standardized 10-point scale, indicating effective management of excessive hunger [9]. Future Development Plans - Following the encouraging Phase II results, Rhythm Pharmaceuticals plans to engage with regulatory authorities in the U.S. and EU to discuss the design of a Phase III study for bivamelagon [10]. - The company aims to request an end-of-phase II meeting with the FDA to pursue a registrational path for bivamelagon [11].

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]