Acadia Pharmaceuticals Halts Development of Prader-Willi Syndrome Drug After Phase III Failure

Acadia Pharmaceuticals has announced the discontinuation of its investigational treatment for hyperphagia in Prader-Willi syndrome (PWS) following disappointing results from a late-stage clinical trial. The decision marks a significant setback in the pursuit of effective therapies for this rare neurological condition.

Phase III COMPASS PWS Trial Results

The Phase III COMPASS PWS trial, which evaluated the efficacy of intranasal carbetocin (ACP-101) in treating hyperphagia associated with PWS, failed to meet its primary endpoint. After 12 weeks of treatment, patients showed no significant change from baseline on the hyperphagia questionnaire for clinical trials (HQ-CT), a key measure of excessive appetite in PWS.

Elizabeth Thompson, head of research and development at Acadia, stated, "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 any further."

Background and Implications

Carbetocin, an oxytocin analogue, was initially developed by Levo Therapeutics and acquired by Acadia in 2022. The drug had shown promise in earlier studies, with a previous Phase III trial (CARE PWS) reporting mixed results – a lower dose met the primary endpoint while a higher dose did not.

The failure of the COMPASS PWS trial represents a significant blow to Acadia's PWS program and highlights the challenges in developing treatments for rare neurological disorders. PWS is believed to result from a deficiency of oxytocin in the brain, making carbetocin a theoretically promising candidate for treatment.

Market Response and Future Outlook

Following the announcement, Acadia's shares dropped nearly 12% in pre-market trading, reflecting investor disappointment in the trial outcome. Analysts from BMO Capital Markets noted that despite COMPASS being more statistically powered through higher enrollment compared to the previous CARE PWS trial, it was insufficient to produce meaningful improvements in clinical outcomes.

With the termination of the PWS program, industry attention is expected to shift towards Acadia's other pipeline candidates. Of particular interest is the ongoing Phase II trial of ACP-204 for psychosis related to Alzheimer's disease, with results anticipated in mid-2026.