Carbetocin nasal spray fails to significantly improve hyperphagia in Prader-Willi syndrome in Phase 3 COMPASS PWS study.

Prader-Willi syndrome (PWS) is a rare genetic disorder marked by severe hyperphagia, anxiousness, and distress. The oxytocinergic system is often dysfunctional in PWS, making it a key therapeutic target. Current treatments often fall short in addressing the profound hyperphagia, which leads to significant morbidity and reduced quality of life. The oxytocin analog carbetocin, with its longer half-life and greater receptor selectivity, previously showed nominally significant improvements in hyperphagia and anxiousness in the Phase 3 CARE-PWS study, warranting further investigation.

The 12-week, randomized, placebo-controlled Phase 3 COMPASS PWS study enrolled 175 participants with PWS. Participants were randomized 1:1 to receive either carbetocin 3.2 mg TID nasal spray (n = 85) or placebo (n = 90). The primary efficacy endpoint was the change from baseline at week 12 in the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Secondary endpoints included changes in Clinical Global Impression-Severity (CGI-S) for PWS and hyperphagia, and CGI-Change for PWS, along with the percentage of HQ-CT responders.