Acadia’s Intranasal Therapy for PWS Fails in Phase 3 Study

Rare Daily Staff

Acadia Pharmaceuticals said top-line results from its phase 3 COMPASS PWS trial of the experimental intranasal therapy ACP-101 to treat hyperphagia in people with Prader-Willi syndrome failed to demonstrate a statistically significant improvement over placebo on the study’s primary endpoint.

The primary endpoint was a change from baseline to Week 12 on the Hyperphagia Questionnaire for Clinical Trials. There was also no separation from placebo on any secondary endpoint. The safety and tolerability profile of intranasal carbetocin was consistent with previous trials, showing a low rate of adverse events.

Prader-Willi syndrome is a rare neurobehavioral genetic disorder that affects both males and females. The condition affects the functioning of the hypothalamus and other aspects of the brain, with symptoms varying by individual. It is typically characterized by hyperphagia, an insatiable appetite and lack of satiety to which a deficiency in oxytocin is believed to contribute. Oxytocin is a natural hormone that regulates several functions in the body, including hunger, anxiety, social behavior, and bonding. Individuals living with Prader-Willi syndrome have fewer neurons that produce oxytocin in the brain. Other defining features of the syndrome may include reduced resting energy expenditure, developmental delays, and behavioral challenges, including anxiety and depression.

ACP-101 is an experimental intranasal formulation of carbetocin being developed for the treatment of hyperphagia in Prader-Willi syndrome. Carbetocin has improved pharmacological qualities relative to oxytocin, including an extended duration of action and greater specificity for oxytocin receptors compared with vasopressin receptors. The formulation of carbetocin was designed to provide direct delivery of the drug to the brain, greatly reducing systemic exposure and the potential for side effects. The U.S. Food and Drug Administration granted ACP-101 orphan drug, fast track, and rare pediatric disease designations.

“Despite this disappointment, Acadia is well-positioned to deliver long-term, sustainable growth supported by two approved products projected to generate more than $1 billion in net sales in 2025, and a robust pipeline that includes eight disclosed and multiple undisclosed programs,” said Catherine Owen Adams, Acadia’s CEO. “Looking ahead, we anticipate seven phase 2 or 3 study starts through 2026, and four data readouts by the end of 2027.”