SUN-724 - Transforming the Burden of Hyperphagia in Bardet-Biedl Syndrome: 6-Month Real-World Outcomes from the RESTORE Study

Background: Hyperphagia and early-onset obesity contribute to substantial burden for patients with Bardet-Biedl Syndrome (BBS), and their families. We present interim real-world patient- and caregiver-reported benefits of setmelanotide on hyperphagia symptoms and impacts, as well as weight management patterns, from the RESTORE study.

Methods: Patients aged ≥6 years old prescribed setmelanotide and enrolled in the Rhythm InTune patient support program, and their caregivers, were invited to participate in RESTORE. Consented participants complete comprehensive electronic surveys assessing medical history, weight management, hyperphagia, and health-related quality of life at baseline (before treatment) and over the first year of treatment. Descriptive analyses were conducted.

Results: A total of 22 participants (mean age: 32.8 ±15.0 years old; female: 77.3%) were actively taking setmelanotide and completed a Month 6 survey as of December 15th, 2025. The prevalence of hyperphagia was high (90.9%; assessed via self-/caregiver-report) prior to setmelanotide initiation. Patients reported rapid reductions in their hyperphagia after one month of setmelanotide treatment, and this reduction was sustained through Month 6, as assessed by the Symptoms of Hyperphagia questionnaire (SoH; range: 0-2 with higher scores indicating greater hyperphagia severity). Among self-reporting participants, the mean change in SoH score from baseline was -0.6 ±0.4 at Month 1 and −0.5 ±0.4 at Month 6. Patients reported the greatest improvements in “feeling hungry after just eating” and “hiding what/how much you were eating from others,” but all domains were improved. The broad negative impacts of hyperphagia, as assessed by the Impacts of Hyperphagia questionnaire (IoH; range: 0-3 with higher scores indicating more negative impacts of hyperphagia), were also reduced after one month of treatment and sustained over six months (mean change: -1.0 ±0.6 at Month 1; -1.1 ±0.4 at Month 6). Patients reported improvements across all domains on the IoH, especially mood/emotions, work/school, and social life. Among all patients, after six months of setmelanotide use, other anti-obesity medication use decreased by 25%, and participants reported positive diet and lifestyle changes, including smaller portion sizes (+42.9%), reduced frequency or quantity of certain foods (+26.7%), and more time spent exercising (+25.1%), relative to baseline.

Conclusions: In real-world settings, patients with BBS treated with setmelanotide experienced meaningful, rapid and sustained reductions in the burden of hyperphagia, improvements in hyperphagia-related quality of life and positive lifestyle changes, which were consistent with reported outcomes from the Phase 3 trial. The six-month evidence from RESTORE further supports the value of timely setmelanotide initiation to comprehensively improve patients’ lives.

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