Rhythm Pharmaceuticals (RYTM) Study Result summary

Study design and patient population

• Open-label phase II trial enrolled 18 Prader-Willi syndrome (PWS) patients aged 6–65 years with severe obesity, including children, adolescents, and adults, treated with setmelanotide for up to 52 weeks.

• Initial patients had severe disease, often with type 2 diabetes, lymphedema, and untreated sleep apnea, and were not eligible for other therapies.

• Dose escalation up to 5 mg/day as tolerated, with younger patients titrated to 3 mg; most tolerated 4–4.5 mg well.

• Background medications included atypical antipsychotics, growth hormone, and Vykat; no patients were on GLP-1s.

• Seventeen of eighteen patients remain on active therapy; one discontinued due to noncompliance and family dynamics.

Efficacy and clinical outcomes

• At Month 3, six of eight patients showed BMI reductions of -1.3% to -4.8%; at Month 6, two exceeded a 5% BMI reduction, with further reductions observed in most patients.

• DEXA scans revealed significant fat mass loss (up to 10%) in some patients, even when BMI plateaued.

• HQ-CT scores reflecting hyperphagia decreased in most patients with elevated baseline scores, indicating improved satiety and reduced food obsession.

• Patients and families reported improved diabetes control, increased activity, better mood, and less food preoccupation.

• Stabilization of BMI in previously rapidly gaining patients was considered a significant clinical benefit.

Safety and tolerability

• Setmelanotide was well tolerated; most common adverse events were hyperpigmentation (27.8%), injection site reactions (22.2%), nausea, headache, and depression.

• No deaths, serious adverse events, or events leading to drug withdrawal were reported.

• No new safety signals emerged; most patients reached target doses without significant issues.

• Safety monitoring included skin exams, depression screening, and growth assessment in pediatric patients.