European Commission expands approval of IMCIVREE (setmelanotide) by Rhythm Pharmaceuticals for acquired hypothalamic obesity, supported by Phase 3 TRANSCEND trial data.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
The European Commission has expanded the marketing authorization for IMCIVREE® (setmelanotide), developed by Rhythm Pharmaceuticals, to treat obesity and control hunger in adults and children aged 4 years and older with acquired hypothalamic obesity (HO).
This decision introduces the first approved pharmacological treatment option in Europe for this rare neuroendocrine condition. The approval follows a recent authorization by the U.S. Food and Drug Administration in March 2026 for the same indication in the United States.
In a company statement, CEO David Meeker said the authorization addresses a major unmet need, noting that hypothalamic dysfunction leads to persistent hyperphagia and rapid, sustained weight gain, with no previously approved therapies available.
The decision is based on results from the Phase 3 TRANSCEND trial (NCT05774756), a global randomized, placebo-controlled study involving 120 patients with acquired HO. The trial met its primary endpoint, showing a statistically significant placebo-adjusted reduction in body mass index (BMI).
Patients treated with setmelanotide (n=81) achieved a 16.5% reduction in BMI from baseline at 52 weeks, compared with a 3.3% increase in the placebo group (n=39), resulting in a placebo-adjusted difference of −19.8% (p<0.0001).
Efficacy was consistent across age groups, with adults achieving a −19.2% placebo-adjusted BMI reduction and pediatric patients achieving a −20.2% reduction at 52 weeks.
The therapy was generally well tolerated, with common adverse events including nausea, vomiting, diarrhea, injection site reactions, skin hyperpigmentation, and headache.
Acquired hypothalamic obesity is caused by injury or dysfunction of the hypothalamus, which disrupts melanocortin-4 receptor (MC4R) pathway signaling responsible for regulating energy balance and body weight.
This disruption leads to uncontrolled hunger and rapid weight gain. The condition often occurs after hypothalamic damage due to tumors such as craniopharyngioma or astrocytoma, or following traumatic brain injury, stroke, inflammation, or structural abnormalities.
Setmelanotide acts by restoring signaling in the MC4R pathway, targeting the underlying disease mechanism.
Rhythm Pharmaceuticals estimates that approximately 10,000 people in Europe are living with acquired HO, and the company plans to pursue country-level access and reimbursement, with commercial launches expected in 2027.
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About the Writer
Chikkula Pavan Kumar, PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.