This is the agency's first approved treatment for acquired hypothalamic obesity.
FDA approved an expanded indication for Imcivree (setmelanotide), making it the first and only approved treatment for acquired hypothalamic obesity, a rare disease that causes severe and unrelenting weight gain following injury to the hypothalamus.
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“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.”
Acquired hypothalamic obesity most commonly develops following the growth or treatment of brain tumors including craniopharyngioma and astrocytoma, as well as traumatic brain injury, stroke, or inflammation affecting the hypothalamus.1
When the hypothalamus is damaged, production of alpha-melanocyte-stimulating hormone is reduced, impairing signaling along the MC4R pathway, the biological system responsible for regulating hunger, energy expenditure, and body weight.1 The result is accelerated and sustained weight gain, often accompanied by severe hyperphagia. Rhythm estimates approximately 10,000 people in the U.S. are living with the condition, which can develop as early as six months after a hypothalamic injury.
Imcivree is now indicated to reduce excess body weight and maintain reduction long-term in adults and pediatric patients aged four and older with acquired hypothalamic obesity.1 The drug works by targeting the MC4R pathway directly, addressing the underlying biological dysfunction rather than symptoms alone.
Imcivree was previously approved in the U.S. and Europe for obesity caused by Bardet-Biedl syndrome and certain genetic deficiencies including POMC, PCSK1, and LEPR.1
The approval is based on the Phase III Transcend trial, which enrolled 142 patients with acquired hypothalamic obesity across global study sites.2 The trial met its primary endpoint, with patients on setmelanotide achieving a 15.8% reduction in BMI at 52 weeks compared to a 2.6% increase among patients on placebo, a placebo-adjusted reduction of 18.4% that was statistically significant. 2
The drug was generally well tolerated, with the most common adverse events being skin hyperpigmentation, nausea, vomiting, and headache.
Ashley Shoemaker, associate professor of pediatric endocrinology at Vanderbilt Health, said patients experienced meaningful reductions in both BMI and hunger, demonstrating clinically significant outcomes in children and adults alike. "Acquired HO is a severe disease that requires early and proactive management," she said.
Until now, patients with acquired hypothalamic obesity had no FDA-approved treatment options, leaving clinicians without a targeted therapy for a condition that can be devastating in quality of life terms.1
Amy Wood, executive director and founder of the Raymond A. Wood Foundation, a patient advocacy organization, said families affected by the disease have long faced relentless hunger and accelerating weight gain with no path forward. " Imcivree offers hope and a path forward for thousands of patients who have long been without options," she said.
