# Setmelanotide

Source: https://onco.cc/drugs/setmelanotide/  
OnCo record `setmelanotide` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Setmelanotide is a daily injection that switches back on the brain's fullness signal. It is approved for rare genetic causes of obesity and, since March 2026 in the United States, for the continuous weight gain that follows damage to the hypothalamus from a tumour such as craniopharyngioma or from its treatment.

## Summary

Setmelanotide is Rhythm Pharmaceuticals' melanocortin-4 receptor agonist. The FDA approved it in 2020 for chronic weight management in obesity due to POMC, PCSK1 or LEPR deficiency, later for Bardet-Biedl syndrome, and on 19 March 2026 for acquired hypothalamic obesity in adults and children aged 4 years and older (Drugs@FDA supplement 9; label revised March 2026). It is injected under the skin once daily and reduces hunger and weight in patients whose hypothalamic satiety pathway is broken upstream of the receptor.

Hypothalamic obesity after craniopharyngioma or other hypothalamic injury is an acquired lesion of the same pathway and resists diet and conventional drugs. After a phase 2 study showed weight loss, the phase 3 TRANSCEND trial (NCT05774756; Miller, NEJM 2026) randomised 120 participants aged 4 to 66 and found a least-squares mean body-mass index change of minus 16.5 percent with setmelanotide against plus 3.3 percent with placebo at 52 weeks, with less hunger, which supported the label expansion. The craniopharyngioma page names it, with GLP-1 agonists and oxytocin, among the treatments for hypothalamic obesity.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-24
- Also known as: RM-493
- Tags: subtype-drugs-wave
- Brand: Imcivree
- Modality: Subcutaneous melanocortin-4 receptor agonist
- Mechanism: Activates the melanocortin-4 receptor downstream of the leptin-POMC pathway in the hypothalamus, restoring the satiety signal that is lost when the hypothalamus is damaged by a craniopharyngioma or its treatment.
- Approvals: US 2020: Chronic weight management in obesity due to POMC, PCSK1 or LEPR deficiency; US 2026: Acquired hypothalamic obesity in adults and children aged 4 years and older

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Setmelanotide
- TRANSCEND (NEJM 2026): https://doi.org/10.1056/NEJMoa2512275
- Imcivree label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9
- Wikipedia: https://en.wikipedia.org/wiki/Setmelanotide

## Connected records

- cancers: [Craniopharyngioma](https://onco.cc/cancers/craniopharyngioma/)
- companies: [Rhythm Pharmaceuticals](https://onco.cc/companies/rhythm-pharmaceuticals/)
- trials: [TRANSCEND](https://onco.cc/trials/transcend/)
- key papers: [Setmelanotide for the treatment of acquired hypothalamic obesity (TRANSCEND)](https://onco.cc/key-papers/paper-transcend-miller-nejm-2026/)

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