Setmelanotide

The labelled product is Imcivree. It is FDA-approved to reduce excess body weight and maintain that reduction in adults and children aged 4 years and older with acquired hypothalamic obesity, and in patients aged 2 years and older with Bardet-Biedl syndrome or with POMC, PCSK1, or LEPR deficiency confirmed by genetic testing. FDA expanded the hypothalamic-obesity use on 19 March 2026. The label says the product is not indicated for general (polygenic) obesity or for other genetic obesity syndromes. Unregulated melanocortin analogs are not Imcivree.

A melanocortin-4 receptor agonist. It is an eight-amino-acid cyclic analog of α-MSH. The labelled uses are rare conditions in which MC4R-pathway signaling is impaired. The labelled use is not a property of melanocortin peptides as a class, and it does not travel to unregulated analogs.

Miller et al. (N Engl J Med 2026, PMID 42418774) reported TRANSCEND, a randomized, placebo-controlled phase 3 trial in acquired hypothalamic obesity (NCT05774756). One hundred twenty participants aged 4 to 66 years were assigned 2:1 to setmelanotide or placebo. The primary endpoint was mean percent change in BMI at 52 weeks: −16.5% with setmelanotide and +3.3% with placebo. Hunger scores also improved. The company approval note of 19 March 2026 cites this program for the hypothalamic-obesity expansion. Earlier labelled uses rest on smaller work: Clément et al. (Lancet Diabetes Endocrinol 2020, PMID 33137293) in POMC or LEPR deficiency, and Haqq et al. (Lancet Diabetes Endocrinol 2022, PMID 36356613) in Bardet-Biedl syndrome. Those programs support the older labelled uses. They do not make setmelanotide a treatment for ordinary obesity.

• Miller et al., TRANSCEND · 2026 · N Engl J Med

  Setmelanotide for the treatment of acquired hypothalamic obesity. N Engl J Med. 2026;395(2):138-150. PMID 42418774. DOI 10.1056/NEJMoa2512275. NCT05774756. PMID 42418774.

• Imcivree (setmelanotide) prescribing information · 2026

  DailyMed label, NDA 213793. Labelled for acquired hypothalamic obesity (age 4+), Bardet-Biedl syndrome (age 2+), and POMC, PCSK1, or LEPR deficiency confirmed by genetic testing (age 2+). Not indicated for general obesity. Setid 70c3ccf7-4df0-4c75-ba07-fede9970c8d9.

• Rhythm, 19 March 2026 approval note · 2026

  FDA approval of an expanded Imcivree indication for acquired hypothalamic obesity. Company announcement, 19 March 2026.

• Clément et al., POMC/LEPR phase 3 · 2020 · Lancet Diabetes Endocrinol

  Setmelanotide in severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre phase 3 trials. Lancet Diabetes Endocrinol. 2020. PMID 33137293. DOI 10.1016/S2213-8587(20)30364-8. PMID 33137293.

• Haqq et al., BBS phase 3 · 2022 · Lancet Diabetes Endocrinol

  Setmelanotide in Bardet-Biedl syndrome and Alström syndrome: multicentre randomised phase 3 trial. Lancet Diabetes Endocrinol. 2022. PMID 36356613. DOI 10.1016/S2213-8587(22)00277-7. PMID 36356613.