Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity
Summary
This pivotal, phase 3 study is designed to confirm the efficacy and safety of setmelanotide, a potent melanocortin receptor type 4 (MC4R) agonist, for the treatment of obesity and hyperphagia in participants with Bardet Biedl syndrome (BBS) or Alström syndrome (AS). The study's primary efficacy endpoint is to evaluate the proportion of participants (≥ 12 years of age at baseline) who lose ≥ 10% of their baseline body weight following approximately (\~) 52 weeks of treatment with setmelanotide compared to a historical control rate.
Timeline
- Start
- 2018-11-23
- Primary completion
- 2020-11-16
- Completion
- 2021-03-08
Outcome
Met primary endpoint
paper In terms of the primary endpoint, 32·3% (95% CI 16·7 to 51·4; p=0·0006) of patients aged 12 years or older with Bardet-Biedl syndrome reached PMID 36356613 ↗
release “individuals with Bardet-Biedl syndrome (BBS) or Alström syndrome. The study met its primary and all key secondary endpoints” rhythmtx.com ↗
release “the Phase 3 trial evaluating setmelanotide in patients with BBS and Alström syndrome met its primary endpoint” rhythmtx.com ↗
release “Rhythm’s Phase 3 trial of setmelanotide in patients with BBS or Alström syndrome met its primary endpoint and all key secondary endpoints” rhythmtx.com ↗
Publications
- Argente J, Haqq AM, Schorfheide JL, Touchot N, Huber C, Wiedemann U, Pomeroy J; Phase 3 BBS Trial Investigators. Setmelanotide in Bardet-Biedl Syndrome: A 52-Week Comparison of Phase 3 Trial Participants With a Matched Registry Cohort. Obesity (Silver Spring). 2026 Mar;34(3):579-587. doi: 10.1002/oby.70125. Epub 2026 Feb 17.
- Ervin C, Norcross L, Mallya UG, Fehnel S, Mittleman RS, Webster M, Haqq AM, Haws RM. Interview-Based Patient- and Caregiver-Reported Experiences of Hunger and Improved Quality of Life with Setmelanotide Treatment in Bardet-Biedl Syndrome. Adv Ther. 2023 May;40(5):2394-2411. doi: 10.1007/s12325-023-02443-y. Epub 2023 Mar 24.
- Forsythe E, Haws RM, Argente J, Beales P, Martos-Moreno GA, Dollfus H, Chirila C, Gnanasakthy A, Buckley BC, Mallya UG, Clement K, Haqq AM. Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results. Orphanet J Rare Dis. 2023 Jan 16;18(1):12. doi: 10.1186/s13023-022-02602-4.
- Haqq AM, Chung WK, Dollfus H, Haws RM, Martos-Moreno GA, Poitou C, Yanovski JA, Mittleman RS, Yuan G, Forsythe E, Clement K, Argente J. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alstrom syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period. Lancet Diabetes Endocrinol. 2022 Dec;10(12):859-868. doi: 10.1016/S2213-8587(22)00277-7. Epub 2022 Nov 7.
- Haws RM, Gordon G, Han JC, Yanovski JA, Yuan G, Stewart MW. The efficacy and safety of setmelanotide in individuals with Bardet-Biedl syndrome or Alstrom syndrome: Phase 3 trial design. Contemp Clin Trials Commun. 2021 May 3;22:100780. doi: 10.1016/j.conctc.2021.100780. eCollection 2021 Jun.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Setmelanotide | Protein / enzyme biologic | 3 mg | Subcutaneous |