Rhythm Pharmaceuticals (RYTM) Study result summary

Study design and patient population

• Phase II open-label trial enrolled 18 patients with Prader-Willi syndrome (PWS) and obesity, aged 6–65 years, with daily setmelanotide dosing up to 5 mg for 52 weeks; 17 completed six months.

• Most patients had severe obesity, challenging behaviors, and comorbidities such as diabetes; many were on growth hormone.

• Both pediatric and adult subgroups showed similar efficacy in BMI reduction and body composition improvements.

• Primary endpoints were safety and tolerability; secondary endpoints included BMI, BMI z-score, hyperphagia, body composition, and pharmacokinetics.

Efficacy results

• Mean BMI decreased by 3.06% at six months; adults saw a 3.11% reduction, and pediatric patients had a mean BMI z-score decrease of -0.35.

• Fat mass decreased by 4.19% on average, with lean mass preserved or increased.

• Eight of ten patients with moderate to severe hyperphagia achieved a ≥7-point reduction in HQCT score.

• Anxiety/distress (PADQ) scores showed clinically meaningful reductions in the majority of patients.

Behavioral and quality of life outcomes

• Consistent improvements in behavior, anxiety, and quality of life reported by caregivers and patients.

• Increased physical activity and social engagement observed, with some patients reducing or discontinuing antipsychotic medications.

• Families valued behavioral improvements and quality of life as much as, or more than, weight loss.