Setmelanotide
Setmelanotide (MC4R agonist)
Also known as: Imcivree
An FDA-approved MC4R agonist for rare genetic forms of obesity driven by defects in the melanocortin pathway.
Overview
Setmelanotide is a selective MC4R agonist approved as Imcivree for obesity caused by specific rare genetic deficiencies (POMC, PCSK1, and LEPR) and for Bardet-Biedl syndrome. It restores signaling in a pathway central to appetite regulation and produces meaningful weight loss in these targeted populations.
Mechanism of action
Selectively agonizes the melanocortin-4 receptor (MC4R) to restore satiety signaling disrupted by upstream genetic defects.
Key studies & citations
- Human2020
Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials
At about one year, 8 of 10 (80%) POMC-deficiency and 5 of 11 (45%) LEPR-deficiency participants lost at least 10% of body weight, with hunger scores down 27% and 44%; hyperpigmentation and injection-site reactions were near-universal.
The Lancet Diabetes & Endocrinology - Human2022
Efficacy and safety of setmelanotide in patients with Bardet-Biedl syndrome and Alstrom syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period
38 patients: 32.3% of those aged 12 or older with Bardet-Biedl syndrome reached at least 10% weight loss after 52 weeks (p=0.0006); results in Alstrom syndrome were inconclusive.
The Lancet Diabetes & Endocrinology - Review2020
FDA approves first treatment for weight management for people with certain rare genetic conditions
November 27, 2020 FDA announcement approving Imcivree for chronic weight management in patients 6 and older with obesity due to POMC, PCSK1 or LEPR deficiency.
U.S. Food and Drug Administration
Frequently asked questions
Is setmelanotide a general weight-loss drug?
No. It is approved specifically for rare genetic obesity syndromes affecting the melanocortin pathway, not for common obesity.