Rhythm Pharma’s IMCIVREE® Secures FDA Approval For Acquired Hypothalamic Obesity After Strong Phase III BMI Reduction Data

Rhythm Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration has approved an expanded indication for IMCIVREE® (setmelanotide) to treat patients with acquired hypothalamic obesity (HO). The label update allows the therapy to be used to reduce excess body weight and support long-term weight maintenance in adults and children aged 4 years and older.

“Setmelanotide has shown effectiveness in targeting the underlying biology of acquired HO,” said Ashley Shoemaker, M.D., MSCI, Associate Professor of Pediatrics, Pediatric Endocrinology at Vanderbilt Health. “Patients treated with setmelanotide experienced meaningful reductions in BMI and hunger, demonstrating the therapy’s ability to deliver clinically significant outcomes in both children and adult patients. Acquired HO is a severe disease that requires early and proactive management. With the availability of IMCIVREE, physicians can offer a targeted therapy.”

Acquired hypothalamic obesity is a rare condition characterised by rapid, persistent weight gain resulting from injury or dysfunction of the hypothalamus. The disorder often develops after brain tumors, related treatments, or other forms of hypothalamic damage. Rhythm estimates that approximately 10,000 individuals in the United States are living with the condition, based on analyses of registry and claims data.

“IMCIVREE is now the first and only FDA-approved therapy for acquired HO, offering a targeted approach that addresses the underlying biology of this disease and meets a critical unmet need for patients who previously had no treatment options,” said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. “This is a transformative milestone for Rhythm and reinforces our commitment to bringing meaningful therapies to patients living with rare MC4R pathway diseases.”

Setmelanotide targets the melanocortin-4 receptor (MC4R) pathway, which regulates hunger, energy balance, and body weight. By restoring signaling in this pathway, the therapy addresses the underlying biological drivers of severe obesity linked to hypothalamic dysfunction.

“Having a therapy for individuals and families affected by acquired hypothalamic obesity has the potential to be transformational,” said Amy Wood, Executive Director and Founder of the Raymond A. Wood Foundation. “We’ve seen firsthand the devastating impact acquired hypothalamic obesity has on patients’ and families’ lives, including relentless hunger and accelerated and sustained weight gain. IMCIVREE offers hope and a path forward for thousands of patients who have long been without options.”

The approval is supported by data from the global Phase III TRANSCEND trial, which enrolled 142 patients with acquired HO. The study met its primary endpoint, demonstrating a statistically significant placebo-adjusted reduction in body mass index of 18.4%. Patients receiving setmelanotide experienced a 15.8% mean reduction in BMI at 52 weeks, compared with a 2.6% increase in the placebo group. The treatment was generally well tolerated, with commonly reported adverse events including skin hyperpigmentation, nausea, vomiting, and headache. IMCIVREE is already approved in the U.S. and Europe for several rare genetic obesity disorders.