Rhythm Pharma's Setmelanotide Receives FDA Priority Review for Acquired Hypothalamic Obesity Treatment

Rhythm Pharmaceuticals announced that the FDA has accepted its supplemental New Drug Application for setmelanotide to treat acquired hypothalamic obesity. The FDA has granted Priority Review and assigned a PDUFA goal date of December 20, 2025. The European Medicines Agency has also confirmed validation of the Marketing Authorization Application for setmelanotide for the same indication. Setmelanotide is a melanocortin-4 receptor agonist previously approved for obesity due to Bardet-Biedl syndrome and POMC, PCSK1 or LEPR deficiencies.

Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company, has announced significant regulatory milestones for its drug candidate setmelanotide. The U.S. Food and Drug Administration (FDA) has accepted for filing a supplemental New Drug Application (sNDA) for setmelanotide seeking approval for the treatment of conditions associated with acquired hypothalamic obesity. The FDA has granted Priority Review and set a Prescription Drug User Fee Act (PDUFA) goal date of December 20, 2025 [1].

Additionally, the European Medicines Agency (EMA) has confirmed validation of the Type II variation submission for setmelanotide's Marketing Authorization Application (MAA) for the same indication. The EMA's Committee for Medicinal Products for Human Use (CHMP) began reviewing the application on August 16, 2025, and is expected to issue an opinion to the European Commission (EC) regarding potential approval [1].

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, was previously approved as IMCIVREE® by the FDA, EMA, and UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) for obesity due to Bardet-Biedl syndrome and POMC, PCSK1 or LEPR deficiencies. The sNDA and Type II Variation are supported by statistically significant and clinically meaningful data from the pivotal Phase 3 TRANSCEND trial of setmelanotide in 120 patients with acquired hypothalamic obesity [1].

Rhythm Pharmaceuticals will host an event, "Commercial Readiness for Acquired Hypothalamic Obesity," on September 24, 2025, in Boston, MA, to review U.S. launch plans and provide insights from leading physicians about the urgent need to treat patients with acquired hypothalamic obesity [1].

Acquired hypothalamic obesity is a rare form of obesity that occurs following physical injury or structural abnormality of the hypothalamus, disrupting the MC4R pathway responsible for controlling energy expenditure, hunger, and weight regulation. It is most frequently caused by craniopharyngioma, astrocytoma, or other hypothalamic-pituitary tumors, traumatic brain injury, stroke, or inflammation. The condition leads to reduced energy expenditure and increased hunger or hyperphagia, resulting in accelerated and sustained weight gain [1].

The Phase 3 TRANSCEND trial demonstrated statistically significant reductions in body mass index (BMI) among patients treated with setmelanotide, with a primary endpoint of mean BMI change from baseline at 52 weeks showing a -19.8% placebo-adjusted reduction. Adult and pediatric patients achieved respective reductions of -19.2% and -20.2% in BMI at 52 weeks [1].

Rhythm Pharmaceuticals is committed to making setmelanotide available to the patient community as quickly as possible. The company estimates there are 5,000 to 10,000 people living with acquired hypothalamic obesity in the U.S. and 3,500 to 10,000 in the EU [1].

References:
[1] https://www.globenewswire.com/news-release/2025/08/20/3136704/0/en/Rhythm-Pharmaceuticals-Announces-FDA-Acceptance-of-sNDA-for-Setmelanotide-in-Acquired-Hypothalamic-Obesity.html