Rhythm Pharmaceuticals announced positive topline results from its Phase 3 TRANSCEND trial of setmelanotide for acquired hypothalamic obesity. The trial met its primary endpoint, demonstrating a statistically significant reduction in BMI in both adult and pediatric patients. Patients receiving setmelanotide achieved a mean BMI change of -16.5% compared to +3.3% for the placebo group at 52 weeks.
This positive data is a significant advancement for patients with acquired hypothalamic obesity, a rare condition with limited treatment options. Current therapies, including lifestyle changes and medications for general obesity, are often ineffective. Setmelanotide offers a targeted approach, addressing the underlying mechanism of the disease by acting on the melanocortin-4 receptor pathway. This targeted mechanism, coupled with the robust clinical results, suggests setmelanotide could become the first approved therapy specifically for this debilitating condition.
The TRANSCEND trial, the largest and longest placebo-controlled study in this patient population, enrolled 120 participants. Results showed a -19.8% placebo-adjusted difference in BMI reduction. Specifically, adult patients saw a -19.2% placebo-adjusted BMI reduction, and those under 18 experienced a -20.2% reduction. Furthermore, 80% of patients on setmelanotide achieved a BMI reduction of 5% or greater at 52 weeks. The safety profile was consistent with previous studies, with common adverse events including nausea, vomiting, diarrhea, injection site reaction, skin hyperpigmentation, and headache. No serious adverse events led to discontinuation.
Rhythm Pharmaceuticals 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. The positive results from this trial represent a potential turning point for patients with acquired hypothalamic obesity. If approved, setmelanotide could significantly improve their quality of life and offer a much-needed treatment option. The success of setmelanotide also strengthens the potential of Rhythm Pharmaceuticals’ next-generation MC4R agonists currently in clinical trials. This development could further expand treatment options for this patient population and solidify Rhythm’s position in this therapeutic area.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
