# TRANSCEND

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

## TL;DR

This phase 3 trial showed that a daily injection which turns the brain's fullness signal back on cut body-mass index by about a sixth, and reduced hunger, in children and adults whose weight gain followed damage to the hypothalamus from a tumour or its treatment, while people on placebo gained weight; it supported the March 2026 US approval of Imcivree for that use.

## Summary

TRANSCEND (NCT05774756; organisation id RM-493-040; US Imcivree label Trial 1) was a multicentre, double-blind, randomised, placebo-controlled phase 3 trial of setmelanotide, a melanocortin-4 receptor agonist, in acquired hypothalamic obesity. Participants were at least 4 years old with a body-mass index at or above the 95th percentile for age and sex (under 18) or at least 30 (18 and over) and a history of a hypothalamic tumour, lesion or injury. They were assigned 2:1 to setmelanotide 1.5 to 3.0 mg or placebo, injected subcutaneously once daily for 52 weeks after a dose-escalation period.

The primary endpoint was the mean percent change in body-mass index from baseline to 52 weeks after the end of dose escalation. In the NEJM 2026 report, 120 participants (81 setmelanotide, 39 placebo; mean age 19.9 years, range 4 to 66) were assigned between April 2023 and March 2025. The least-squares mean change in body-mass index was minus 16.5 percent (95 percent CI minus 19.3 to minus 13.8) with setmelanotide and plus 3.3 percent (minus 0.6 to 7.2) with placebo (P less than 0.001). Among participants aged 12 and older, the least-squares mean change in the weekly average of maximal daily hunger scores (0 to 10) was minus 2.73 versus minus 1.45 (P = 0.009). Adverse events occurred in 100 percent of the setmelanotide group and 90 percent of the placebo group, serious adverse events in 28 percent and 8 percent; skin hyperpigmentation, nausea, vomiting and headache were the commonest events with setmelanotide.

The FDA approved the acquired hypothalamic obesity indication for patients aged 4 years and older on 19 March 2026 (Drugs@FDA supplement 9). The registry lists the trial as active, not recruiting, with completion expected in 2027, and its condition is hypothalamic obesity rather than a corpus cancer, which is why the automated pass never attached it to the setmelanotide record.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-24
- Also known as: RM-493-040; RM-493 040; Trial 1
- Registry id: NCT05774756
- Phase: 3
- Setting: Acquired hypothalamic obesity after a hypothalamic tumour, lesion or injury in people aged 4 years and older: setmelanotide 1.5 to 3.0 mg versus placebo, injected under the skin once daily for 52 weeks after dose escalation
- Sponsor: Rhythm Pharmaceuticals
- Enrolled: 120
- Result: Least-squares mean change in body-mass index at 52 weeks minus 16.5% with setmelanotide vs plus 3.3% with placebo (P<0.001); hunger score change minus 2.73 vs minus 1.45 (P = 0.009).
- Outcomes: Mean percent change in body-mass index at 52 weeks after dose escalation (pivotal cohort): Setmelanotide 1.5 to 3.0 mg daily -16.5% vs Placebo 3.3%; Change in the weekly average of maximal daily hunger score at 52 weeks (participants aged 12 and older; scale 0 to 10): Setmelanotide 1.5 to 3.0 mg daily -2.73 points vs Placebo -1.45 points
- Replication: A phase 2 open-label study (Roth 2024, NCT04725240) had shown weight loss in acquired hypothalamic obesity; TRANSCEND is the first randomised confirmation. The genetic-obesity pivotals for the same drug are separate programmes.

## Sources

- ClinicalTrials.gov NCT05774756: https://clinicaltrials.gov/study/NCT05774756
- 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

## Connected records

- cancers: [Craniopharyngioma](https://onco.cc/cancers/craniopharyngioma/)
- fronts: [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- drugs: [Setmelanotide](https://onco.cc/drugs/setmelanotide/)
- companies: [Rhythm Pharmaceuticals](https://onco.cc/companies/rhythm-pharmaceuticals/)
- 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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