A Trial of Setmelanotide in Acquired Hypothalamic Obesity

Summary

The goal of this trial is to learn how well Setmelanotide works to improve weight reduction, hunger, and quality of life in patients 4 years of age and older with acquired Hypothalamic Obesity (HO). To determine how well setmelanotide works and how safe it is, patients with HO will take a daily injection of either setmelanotide or placebo and complete trial assessments for 52 weeks on a therapeutic regimen. A separate sub-study in patients with congenital HO is detailed under NCT06760546.

Timeline

Start

2023-04-26

Primary completion

2025-03-18

Completion

2027-04-16

Outcome

Met primary endpoint

registry analysis (other test); Setmelanotide vs Placebo; p <0.0001; Least square mean difference -19.83 (95% CI -24.55 to -15.10); ANCOVA NCT05774756 ↗

paper The least-squares mean (LSM) change in BMI at 52 weeks was -16.5% (95% confidence interval [CI], -19.3 to -13.8) with setmelanotide and 3.3% (95% CI, -0.6 to 7.2) with placebo (P<0.001) PMID 42418774 ↗

release “its pivotal Phase 3 trial evaluating setmelanotide for the treatment of acquired hypothalamic obesity met its primary endpoint with a -19.8% placebo-adjusted BMI reduction” rhythmtx.com ↗

release “TRANSCEND trial met its primary and key secondary endpoints” rhythmtx.com ↗

release “Phase 3 TRANSCEND trial of setmelanotide in acquired HO. The global study met its primary endpoint” rhythmtx.com ↗

Publications

• Miller JL, van Santen HM, Phillips SA, Hamilton J, Aberle J, Sathyapalan T, Mohamed Z, McCormack SE, Shoemaker AH, Kelsey MM, Ghalib L, Stalla G, Thaker VV, Habiby R, Ode KL, Wabitsch M, Dattani M, Abuzzahab MJ, Abdullatif H, Morgan R, Stefater-Richards M, Aroda VR, Friedrich C, Han JC, Ono H, Nagasaki K, Tanaka T, Isojima T, Arima H, Scimia C, Yuan G, Muller HL, Roth CL; TRANSCEND Trial Group. Setmelanotide for the Treatment of Acquired Hypothalamic Obesity. N Engl J Med. 2026 Jul 9;395(2):138-150. doi: 10.1056/NEJMoa2512275.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Setmelanotide	Protein / enzyme biologic	1.5 mg	Subcutaneous
Subject	Setmelanotide	Protein / enzyme biologic	3 mg	Subcutaneous

Indications