FDA Set Review Date for Imcivree for Rare Form of Obesity

The FDA has accepted Rhythm Pharmaceuticals' supplemental new drug application (sNDA) for Imcivree (setmelanotide), seeking approval to treat patients with conditions associated with acquired hypothalamic obesity. The FDA has granted priority review of the sNDA and assigned a Prescription Drug User Fee Act (PDUFA) goal date of Dec. 20, 2025.

Acquired hypothalamic obesity is a rare form of obesity that occurs after a physical injury or structural abnormality of the hypothalamus, a region of the brain responsible for energy balance, autonomic nervous system regulation, circadian rhythm and controlling pituitary hormones. The hypothalamus can be injured during surgery to remove brain tumors or as a result of head trauma, infections, radiation or bleeding in the brain.

The MC4R pathway is responsible for controlling physiological functions such as energy expenditure, hunger and weight regulation. Impairment of the MC4R pathway can lead to reduced energy expenditure and increased hunger, leading to accelerated and sustained weight gain, most commonly beginning within six to 12 months following injury.

David Meeker, M.D.

“Treatment approaches indicated for general obesity offer limited long-term efficacy for patients living with acquired HO, who face unique challenges including reduced energy expenditure and increased hunger or hyperphagia specifically resulting from MC4R pathway impairment due to hypothalamic injury,” David Meeker, M.D., chairman, CEO and president of Rhythm, said in a news release.

Imcivree is currently approved by the FDA for weight management in patients with Bardet-Biedl syndrome (BBS), a rare genetic disorder, as well as adult and pediatric patients 6 years old and older with obesity due to POMC, PCSK1 or LEPR deficiency. Deficiencies in POMC, PCSK1, and LEPR also affect the MC4R pathway.

The sNDA is based on data from the pivotal phase 3 TRANSCEND trial of setmelanotide in 120 patients age 4 years and older with acquired hypothalamic obesity. The primary endpoint was mean percent change in body mass index (BMI) from baseline after 52 weeks of treatment.

Secondary endpoints are assessing daily hunger, hyperphagia (extreme unsatisfied drive to consume food), weight, quality of life and safety and tolerability. Topline results from TRANSCEND, were presented in an oral session at the Endocrine Society’s Annual Meeting in April 2025.

The global study met its primary endpoint, with a statistically significant -19.8% placebo-adjusted reduction in BMI. For the primary endpoint of mean BMI change from baseline, patients on setmelanotide therapy achieved a -16.5% reduction compared with a +3.3% increase among patients on placebo at 52 weeks. Adult patients achieved a -19.2% placebo-adjusted BMI reduction at 52 weeks, and pediatric patients achieved a -20.2% placebo-adjusted BMI reduction at 52 weeks.

Setmelanotide was generally well tolerated in the TRANSCEND study. The most common treatment-emergent adverse events were nausea, vomiting, diarrhea, injection site reaction, skin hyperpigmentation and headache.

Of the 106 patients who completed the study, 101 enrolled in an open-label extension.

The therapy is also being studied in a phase 3 trial in patients with congenital hypothalamic obesity substudy.