Rhythm Pharmaceuticals Announces Positive Data from Phase 3 Trial of Setmelanotide in Acquired Hypothalamic Obesity

18.8% placebo-adjusted difference in BMI reduction achieved in all patients at 52 weeks, including Japanese and supplemental cohorts

Mar. 2, 2026 at 10:23pm

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Rhythm Pharmaceuticals, Inc. announced additional positive data from its global Phase 3 TRANSCEND trial of setmelanotide in patients with acquired hypothalamic obesity. The new data set includes 12 patients from a Japanese cohort and 10 supplemental patients, in addition to the primary 120-patient pivotal cohort. The trial achieved an 18.8% placebo-adjusted difference in BMI reduction at 52 weeks across all 142 patients.

Why it matters

Acquired hypothalamic obesity is a rare disease characterized by accelerated and sustained weight gain caused by an injury to the hypothalamus, which can lead to decreased alpha-melanocyte-stimulating hormone production and impairment of the MC4R pathway. These positive results further support setmelanotide's potential to become the first approved therapy for patients living with the hunger, reduced energy expenditure, and obesity associated with acquired hypothalamic obesity.

The details

The Phase 3 TRANSCEND trial met its primary and key secondary endpoints, demonstrating a primary endpoint of mean BMI reduction of -16.4% from baseline for all patients on setmelanotide therapy (n=94) compared with +2.4% BMI change for patients on placebo (n=48) at 52 weeks. Among patients aged 12 and older (n=98), the setmelanotide group (n=66) showed an average weekly reduction of 2.5 points in the weekly average most hunger score, compared with a 1.3-point reduction in the placebo group (n=32).

  • Rhythm's supplemental New Drug Application (sNDA) is under review by the U.S. Food and Drug Administration (FDA) with a PDUFA goal date of March 20, 2026.
  • Rhythm will submit the final data package to the FDA on March 2, 2026 ahead of the previously agreed upon submission date for the supplemental data.
  • The European Medicines Agency (EMA) is reviewing Rhythm's Type II variation submission to the Marketing Authorization Application (MAA) for setmelanotide for the same indication, with the Committee for Medicinal Products for Human Use (CHMP) expected to issue an opinion to the European Commission (EC) in the second quarter of 2026 and potential marketing authorization in the second half of 2026.
  • Rhythm plans to submit the full data package to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) and seek marketing authorization for setmelanotide to treat acquired hypothalamic obesity there.

The players

Rhythm Pharmaceuticals, Inc.

A global commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases.

David Meeker, M.D.

Chairman, Chief Executive Officer and President of Rhythm Pharmaceuticals.

U.S. Food and Drug Administration (FDA)

The regulatory agency that is reviewing Rhythm's supplemental New Drug Application (sNDA) for setmelanotide to treat acquired hypothalamic obesity.

European Medicines Agency (EMA)

The regulatory agency that is reviewing Rhythm's Type II variation submission to the Marketing Authorization Application (MAA) for setmelanotide to treat acquired hypothalamic obesity.

Pharmaceuticals and Medical Devices Agency (PMDA)

The regulatory agency in Japan that Rhythm plans to submit the full data package to and seek marketing authorization for setmelanotide to treat acquired hypothalamic obesity.

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What they’re saying

“Building off our strong pivotal data, these efficacy data further support setmelanotide's potential to become the first therapy approved for patients living with the hunger, reduced energy expenditure, accelerated weight gain, and obesity of acquired hypothalamic obesity.”

— David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm Pharmaceuticals (Globe Newswire)

What’s next

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The takeaway

These positive results from the Phase 3 TRANSCEND trial highlight setmelanotide's potential to become the first approved therapy for patients living with the debilitating effects of acquired hypothalamic obesity, a rare disease characterized by uncontrolled weight gain and hunger. Rhythm is well-prepared to bring this important new treatment option to patients, pending regulatory approvals in the U.S., Europe, and Japan.