Melanocortins

Setmelanotide

RM-493; Imcivree

US status
FDA-approved
Class
Melanocortins
Approved product
Imcivree (2020)
Route
Subcutaneous injection

By Diane Walker · Reference Editor · Reviewed September 2026

Regulatory record

3 dated actions on record.
November 2020
FDA approves setmelanotide injection under new drug application 213793, approval dated November 25, 2020, as a Type 1 new molecular entity. Drugs@FDA records the product as Imcivree, a subcutaneous solution containing setmelanotide acetate at a strength of 10 mg base per mL, sponsored by Rhythm and marketed as prescription-only.
March 2026
Drugs@FDA records three approved efficacy supplements to the application after the original approval, dated June 16, 2022, December 20, 2024 and March 19, 2026, alongside two labeling supplements. The label in effect on April 1, 2026 indicates the product to reduce excess body weight and maintain weight reduction long term in patients aged four years and older with acquired hypothalamic obesity, and aged two years and older with obesity due to Bardet-Biedl syndrome or to confirmed proopiomelanocortin, proprotein convertase subtilisin/kexin type 1 or leptin receptor deficiency.
September 2026
Setmelanotide sits in no category of the 503A bulks list published May 14, 2026 and on no 503B list. An approved product exists, so the question the bulks list answers does not arise for it.

Every entry above is dated; the record is current as of the review date.

Definition

Setmelanotide is a synthetic melanocortin 4 receptor agonist marketed as Imcivree. It acts on the same receptor pathway as PT-141 and Melanotan II, and unlike either of them it was developed for body weight rather than for sexual function or pigmentation.

The distinction that matters here is not chemical but regulatory. Setmelanotide is an approved obesity drug whose label excludes ordinary obesity, which makes it the clearest case in this index of an approval that is narrower than the condition it appears to treat.

Evidence

The trial record is the development program and it is small by design, because the populations are rare. Across four name variants PubMed returns 243 indexed records, of which 153 carry the Humans subject heading, 19 the clinical-trial publication type and 6 the randomized-controlled-trial type [1]. All nineteen were opened and read; seventeen name the molecule and two are matches on the search rather than on the compound, a puberty adipose-depot study and an intranasal oxytocin proteomics paper [1].

The registrational evidence is two single-arm phase 3 trials in leptin receptor or proopiomelanocortin deficiency [2], and a randomized, double-blind, placebo-controlled phase 3 trial in Bardet-Biedl and Alström syndromes [3]. A single-arm design is what a disease affecting a few hundred identified patients permits; it is also a weaker instrument than a controlled one, and the label rests on both kinds.

The indication has widened twice since approval and each widening carries its own trial. A one-year open-label phase 3 extended the population down to children aged two to five years [4], and acquired hypothalamic obesity was added on the strength of a phase 2 followed by a randomized trial reported in 2026 [5]. The earliest human work in the set is a 2015 study measuring resting energy expenditure in obese adults [6], which is the pharmacology rather than the indication.

Lawful access

The lawful supply route is the approved product. FDA approved setmelanotide injection under new drug application 213793 on November 25, 2020 as a Type 1 new molecular entity, and Drugs@FDA records Imcivree as a subcutaneous solution of setmelanotide acetate at 10 mg base per mL, sponsored by Rhythm and marketed as prescription-only [7]. Three efficacy supplements have been approved since, dated June 16, 2022, December 20, 2024 and March 19, 2026 [7].

The label states who it is for, and states separately who it is not for. In the version effective April 1, 2026 the product is indicated "to reduce excess body weight and maintain weight reduction long term" in patients aged four years and older with acquired hypothalamic obesity and aged two years and older with obesity due to Bardet-Biedl syndrome or to confirmed proopiomelanocortin, proprotein convertase subtilisin/kexin type 1 or leptin receptor deficiency [8]. Its limitations of use say the product "is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective", and name among them "[o]ther types of obesity not related to acquired HO, BBS or POMC, PCSK1 or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity" [8].

Compounding does not arise for this molecule. Setmelanotide sits in no category of the section 503A bulks list published May 14, 2026 and on no 503B list [9]; an approved product exists, which is the condition under which the bulks question is not asked. No supplier is listed here, and the rail is empty because no approved program on this profile has been verified as offering it.

Elsewhere in this index

Filed under

Reference tables

Same class

References

  1. PubMed, National Library of Medicine. Census run 2026-09-02 across four name variants — "setmelanotide" OR "RM-493" OR "RM 493" OR "Imcivree" — returning 243 indexed records, 153 carrying the Humans MeSH term, 19 under "clinical trial"[Publication Type] and 6 under "randomized controlled trial"[Publication Type]. All 19 trial-type records were retrieved and read individually rather than counted: 17 name a variant in the title or abstract, and 2 do not and are artifacts of the search — a puberty adipose-depot study and an intranasal oxytocin proteomics paper. The publication-type filter was proved live in the same run against a control term returning 8,907 records under the clinical-trial type and 6,116 under the randomized type; the invalid tag clinicaltrial[pt] returned 0 for that control term in the same run, and a deliberately invalid record identifier errored in the same run. Source
  2. Clément K, van den Akker E, Argente J, et al. 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. Lancet Diabetes Endocrinol. 2020;8(12):960–970. PMID 33137293
  3. Haqq AM, Chung WK, Dollfus H, et al. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period. Lancet Diabetes Endocrinol. 2022;10(12):859–868. PMID 36356613
  4. Argente J, Verge CF, Okorie U, et al. Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial. Lancet Diabetes Endocrinol. 2025;13(1):29–37. PMID 39549719
  5. Miller JL, van Santen HM, Phillips SA, et al. Setmelanotide for the Treatment of Acquired Hypothalamic Obesity. N Engl J Med. 2026;395(2):138–150. PMID 42418774
  6. Chen KY, Muniyappa R, Abel BS, et al. RM-493, a melanocortin-4 receptor (MC4R) agonist, increases resting energy expenditure in obese individuals. J Clin Endocrinol Metab. 2015;100(4):1639–1645. PMID 25675384
  7. Drugs@FDA, US Food and Drug Administration. Application NDA 213793, IMCIVREE (setmelanotide acetate), sponsor Rhythm; subcutaneous solution, EQ 10MG BASE/ML, marketing status Prescription. Original approval recorded November 25, 2020, submission class Type 1 - New Molecular Entity; approved efficacy supplements dated June 16, 2022, December 20, 2024 and March 19, 2026, and labeling supplements dated November 15, 2023 and August 21, 2025. Read 2026-09-02 through the openFDA drugsfda endpoint, in a run whose control query on a nonexistent ingredient returned no match. Source
  8. IMCIVREE (setmelanotide) injection, prescribing information, structured product label version 14, effective April 1, 2026. Sections 1 Indications and Usage and 1.1 Limitations of Use. Read 2026-09-02 through the openFDA label endpoint. Source
  9. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act, US Food and Drug Administration, face date "Updated May 14, 2026". Read 2026-09-02. Setmelanotide appears in none of the three categories; the document's Category 1 table was extracted in full and searched, in a run whose positive control term appeared and whose nonsense control term did not. Source

The editor is not a licensed clinician; this monograph is a regulatory and evidence reference, not medical advice. Statuses are re-verified on the date shown, and every quantitative claim resolves to a numbered reference. Corrections: editor@peptideamerica.org. See how this reference is funded.