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Section 1 of 7Overview
Overview
Setmelanotide (brand Imcivree; development codes RM-493 / BIM-22493) is a prescription melanocortin-4 receptor (MC4R) agonist — a cyclic eight-amino-acid analogue of α-MSH. PubChem CID 11993702; formula C₄₉H₆₈N₁₈O₉S₂; free-base MW 1117.3 Da; CAS 920014-72-8.
It is approved in the United States (FDA, November 2020; label revised March 2026) and the European Union (EMA central MA, July 2021) for rare obesity driven by disruption of the MC4R pathway — not for common polygenic obesity.
Not Melanotan II, not PT-141
- Melanotan II — non-selective melanocortin research/cosmetic peptide; not an approved obesity medicine.
- PT-141 (bremelanotide / Vyleesi) — FDA-approved for HSDD in premenopausal women, not for obesity.
- Melanotan I — separate melanocortin analogue lineage; do not equate with Imcivree.
Setmelanotide is indication-bound prescription therapy with genetic/clinical selection criteria on the label.
Section 2 of 7Regulatory indications (label-level)
Regulatory indications (label-level)
United States (FDA label 03/2026)
Chronic weight management in patients with obesity due to:
- Acquired hypothalamic obesity (HO) — age ≥4 years
- Bardet–Biedl syndrome (BBS) — age ≥2 years
- POMC, PCSK1, or LEPR deficiency — pathogenic / likely pathogenic / VUS variants as defined on the label — age ≥2 years
Limitations of Use: not indicated for other types of obesity including polygenic / general obesity, or for obesity due to benign gene variants.
European Union (EMA)
Central marketing authorisation for Imcivree covers obesity and hunger control in genetically confirmed BBS and biallelic POMC (including PCSK1) / LEPR pathway disease, with EPAR updates that may include HO — confirm the current SmPC for exact age bands and HO wording at time of use. This page’s primary US detail follows the March 2026 FDA label.
Section 3 of 7Label dosing (citation only)
Label dosing (citation only)
Starting and maintenance doses differ by indication and age and are defined only by the official labels; they are not reproduced here: IMCIVREE prescribing information (DailyMed) (opens in a new tab) and Imcivree EPAR (EMA) (opens in a new tab). Not a self-use protocol.
Section 4 of 7Key trials (selected)
Key trials (selected)
| Study | Population | Headline result | Source |
|---|---|---|---|
| Clément 2020 | POMC/PCSK1 and LEPR deficiency, phase 3 | ≥10% weight loss at ~1 year in 80% (POMC/PCSK1, n=10) and 46% (LEPR, n=11) | PMID 33137293 |
| Haqq 2022 | BBS (± Alström), phase 3 | Active-treatment BMI change ~−7.9% at 52 weeks; placebo-corrected ~−4.5% at 14 weeks | PMID 36356613 |
| Roth 2024 | Acquired HO, phase 2 open-label | Proof-of-concept for HO | PMID 38697184 |
| TRANSCEND / Miller 2026 | HO ≥4 years, phase 3 RCT | LSM BMI −16.5% vs +3.3% placebo at 52 weeks; hunger reduced | PMID 42418774; NCT05774756 |
Section 5 of 7Safety highlights (label)
Safety highlights (label)
Common adverse reactions include hyperpigmentation, injection-site reactions, nausea, headache, and GI symptoms. Label warnings address depression / suicidal ideation (monitor), spontaneous erections, and new or darkening nevi (skin exam). For hypothalamic obesity, label text also covers risks such as acute adrenal insufficiency and sodium imbalance in central diabetes insipidus. Unlike the GLP-1 class, setmelanotide does not carry a thyroid C-cell boxed warning.
Section 6 of 7Claims vs evidence
Claims vs evidence
| Claim | Assessment |
|---|---|
| Approved MC4R agonist for rare pathway obesity (US/EU) | Supported |
| Works for general / polygenic obesity | False / off-label — Limitations of Use |
| Same as Melanotan II | False |
| Replaces Vyleesi for HSDD | False — different indication |
| Label dose = research self-use dose | Reject |