PWS-related hyperphagia drug ACP-101 fails to meet trial goals
Acadia Pharmaceuticals will stop development of experimental nasal spray
A Phase 3 clinical trial testing ACP-101 for hyperphagia, or uncontrollable hunger, in Prader-Willi syndrome (PWS) patients failed to meet its primary and secondary goals.
Top-line results from the trial of Acadia Pharmaceuticals’ experimental nasal spray, dubbed COMPASS PWS (NCT06173531), showed no significant differences between the ACP-101 and placebo groups in terms of hyperphagia-related behaviors and other disease measures.
“We are disappointed by these findings, especially for Prader-Willi syndrome patients, their families, and the entire community,” Elizabeth H.Z. Thompson, PhD, Acadia’s head of research and development, said in a company press release. “We are committed to sharing a summary of the data in the future to ensure learning for the PWS community; however, given these results, we do not intend to investigate intranasal carbetocin [ACP-101] any further.”
ACP-101 aimed to provide substitute for oxytocin
In PWS, genetic defects in a particular section of chromosome 15 cause a range of symptoms, including slowed growth, behavioral issues, and hyperphagia. The latter can result in overeating and obesity, potentially posing health risks.
PWS impairs the brain’s production of oxytocin, a hormone that plays a critical role in appetite control and helps regulate social and emotional behaviors.
With ACP-101, Acadia aimed to provide a substitute for oxytocin, which the company expected to regulate appetite and other behaviors. The nasal spray formulation, originally developed by Levo Therapeutics under the name LV-101, contained a lab-made version of oxytocin called carbetocin.
Previous Levo Therapeutics-sponsored clinical trials of the nasal spray formulation of carbetocin had mixed results. For example, the Phase 3 CARE-PWS trial (NCT03649477) found no significant effects in participants who received a higher dose of the medication (9.6 mg), but a significant reduction of hyperphagia with the 3.2 mg dose.
The U.S. Food and Drug Administration considered these results to be insufficient to grant approval to ACP-101 and asked for another trial to confirm its benefits, which COMPASS PWS was designed to accomplish.
Trial failed to meet primary, secondary goals
The Acadia-sponsored COMPASS PWS evaluated the safety and efficacy of 3.2 mg of ACP-101 against a placebo in up to 175 people with PWS ages 5 to 30. Participants were randomly assigned to inhale either the therapy or a placebo three times a day for 12 weeks, or about three months.
The trial’s main goal was to assess whether ACP-101 was superior to the placebo at easing hyperphagia-related behaviors, as measured with the caregiver-reported Hyperphagia Questionnaire for Clinical Trials score. Secondary goals included changes in clinicians’ and caregivers’ impressions of PWS severity.
Top-line data demonstrated no significant differences in terms of primary and secondary goals between participants treated with ACP-101 and those given a placebo, indicating no considerable benefit from the experimental therapy.
Although COMPASS PWS was unsuccessful and Acadia will not continue developing ACP-101, the company expressed gratitude for those who contributed to the trial.
“I want to thank the many patients, families, study site personnel, and physicians who participated in the COMPASS PWS study, as well as the intranasal carbetocin clinical development program, for their dedication and contributions in this important study,” Thompson said.
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