Rhythm Pharmaceuticals Reports Positive Phase 2 Results for Setmelanotide in Prader-Willi Syndrome
核心洞察
Rhythm Pharmaceuticals announced positive preliminary results from its exploratory Phase 2 trial of setmelanotide in Prader-Willi syndrome (搜索), showing BMI and hyperphagia (搜索) reductions at Month 3 and Month 6.
Six of eight patients achieved BMI reductions at Month 3, while six of seven evaluable patients showed meaningful reduction in hyperphagia (搜索) scores, with 17 of 18 enrolled patients remaining on therapy.
The company plans to advance setmelanotide into a Phase 3 registrational trial for PWS (搜索) and has initiated a Phase 1 study of weekly MC4R (搜索) agonist RM-718 in PWS patients.
Rhythm Pharmaceuticals announced positive preliminary results from its exploratory Phase 2 trial of setmelanotide in patients with Prader-Willi syndrome (搜索) (PWS (搜索)), demonstrating reductions in both body mass index (BMI) and hyperphagia (搜索) in treated patients. The company plans to advance the MC4R (搜索) agonist into a Phase 3 registrational trial based on these encouraging results.
Trial Results Show Promise for PWS Treatment
The single-site, open-label Phase 2 study enrolled 18 patients with PWS (搜索) aged 6-65 years with a BMI ≥30 kg/m² for patients ≥18 years of age or BMI ≥95th percentile for age and sex for patients younger than 18. Participants were dose-escalated to 5 mg/day of setmelanotide as tolerated in the ongoing 52-week trial.
Key efficacy findings from the preliminary data, with a cut-off date of November 14, included:
- Six of eight patients who reached Month 3 of setmelanotide therapy achieved BMI reductions from baseline
- Three of five patients who reached Month 6 achieved BMI reductions, with two seeing deeper reductions versus Month 3 and one unchanged
- Six of seven evaluable patients who reached Month 3 achieved meaningful reduction in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) scores
- Seventeen of the 18 patients enrolled remain on active setmelanotide therapy
"There remains a profound unmet need in the PWS (搜索) patient population," said Jennifer Miller, M.D., University of Florida Division of Endocrinology, Department of Pediatrics in the College of Medicine, the principal investigator for this Phase 2 trial. "Hyperphagia (搜索) and severe obesity (搜索) associated with PWS present serious challenges for patients and often lead to significant health complications over time."
Safety Profile Consistent with Established Data
Safety and tolerability results have been consistent with setmelanotide's well-established clinical profile. The drug's most common adverse reactions (incidence ≥20%) include skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
Expanding Development Program
Rhythm also announced the initiation of a Part D arm in the Phase 1 trial of MC4R (搜索) agonist RM-718 that will enroll up to 20 patients with PWS (搜索). The company anticipates screening the first patient for this 26-week open-label trial of the weekly MC4R agonist in December 2025.
"We are encouraged by these preliminary results, which give us confidence to advance setmelanotide into a registrational Phase 3 trial for PWS (搜索)," said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. "We look forward to additional data in the first half of 2026 and remain committed to exploring the potential of MC4R (搜索) agonism for this patient population."
Addressing Significant Unmet Medical Need
PWS (搜索) is a rare genetic disorder that results in physical, mental and behavioral problems, with a constant sense of hunger typically beginning around age 2. The condition is estimated to affect approximately 400,000 people worldwide and approximately 20,000 people in the United States. Currently, there are limited therapeutic options that effectively reduce the extreme hyperphagia (搜索) and address low resting energy expenditure associated with PWS.
Setmelanotide is currently approved by the FDA to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients 2 years of age and older with syndromic or monogenic obesity (搜索) due to Bardet-Biedl syndrome (搜索) or genetically confirmed POMC (搜索), PCSK1 (搜索), or LEPR (搜索) deficiency. The European Commission and UK's MHRA have also authorized the drug for similar indications.