Rhythm Pharmaceuticals recently shared encouraging six-month results from its ongoing Phase 2 clinical trial of setmelanotide in people with Prader-Willi syndrome (PWS). The findings, presented at ENDO 2026, suggest that treatment with setmelanotide may help improve not only weight and body composition but also hyperphagia, anxiety, and some behavioral symptoms.
What is Setmelanotide?
Setmelanotide is a medication that activates the melanocortin-4 receptor (MC4R) pathway, which is important in regulating hunger and energy balance. The drug has been approved for several rare genetic forms of obesity, and Rhythm is now evaluating whether it may also benefit people with PWS.
What Did the Six-Month Data Show?
The ongoing study enrolled 18 individuals with PWS between the ages of 6 and 65. Six-month data were available for 17 participants. Researchers reported several encouraging findings:
- Participants experienced an average 3.1% reduction in BMI (body mass index).
- Body fat decreased by an average of 4.2%, while lean muscle mass was preserved.
- Among participants with moderate-to-severe hyperphagia, most showed meaningful improvements in food-related behaviors and hunger.
- Researchers also observed improvements in anxiety and behavioral measures
Importantly, the safety profile observed in the study was generally consistent with what has been seen in previous setmelanotide trials. The most commonly reported side effects were injection site reactions (reported in 61% of participants) and skin hyperpigmentation, or darkening of the skin (56%). No new safety concerns were identified during the six-month study period.
While these results are promising, this remains an early-stage study. Additional participants are continuing treatment, and longer-term data will help researchers better understand the potential benefits and risks of the therapy. Rhythm has indicated that these results support advancing setmelanotide into Phase 3 development for PWS.
Where Can You Learn More About Setmelanotide and PWS?
Families interested in exploring the data in greater detail can access Rhythm's original announcement and listen to the investor webcast:
- Read Rhythm's full press release: Rhythm Pharmaceuticals Presents Positive Interim Six-Month Data from Phase 2 Trial of Setmelanotide in Patients with Prader-Willi Syndrome (PWS) at ENDO 2026
- Listen to the recorded investor webcast and Q&A discussion: Recorded Investor Call and Webcast
The webcast includes additional discussion of the six-month findings, behavioral outcomes, plans for a Phase 3 trial of setmelanotide in PWS, and updates on Rhythm's broader MC4R development program, including RM-718.
Interested in Participating in a Clinical Trial?
While the current Phase 2 setmelanotide study is no longer enrolling new participants, Rhythm is actively recruiting individuals ages 12 to 65 years with obesity and PWS to participate in the RM-718 clinical trial. RM-718 is a next-generation MC4R agonist designed as a once-weekly injection that may offer greater convenience compared to the daily injections used with setmelanotide.
Families interested in learning more about RM-718, including eligibility and study locations, can visit our blog: New Study Opportunity for Prader-Willi Syndrome: Now Enrolling RM-718
