Acadia Pharmaceuticals announced on November 30, 2023, the initiation of its pivotal Phase 3 COMPASS PWS clinical trial evaluating carbetocin nasal spray (ACP-101) for the treatment of hyperphagia in patients with Prader-Willi syndrome (PWS).
The trial addresses a significant unmet need for the estimated 8,000 to 10,000 patients in the United States living with PWS, a rare neurobehavioral genetic disorder characterized primarily by hyperphagia—an unrelenting sensation of hunger despite adequate food intake.
"Currently there is no FDA-approved treatment for hyperphagia in PWS, which presents serious challenges for those living with this condition and their families," said Dr. Shawn McCandless, Chair of the Department of Genetics and Metabolism at Children's Hospital Colorado and COMPASS PWS study investigator. "Essentially all experience hyperphagia, feeling a near-constant state of hunger, as though their body is telling them that they are starving, despite being actually well-nourished."
Dr. McCandless emphasized the life-threatening risks associated with the condition, including "gastric rupture, irregular swallowing and choking," which necessitate constant supervision of affected individuals.
Trial Design and Endpoints
COMPASS PWS is designed as a 12-week, double-blind, randomized, placebo-controlled global Phase 3 trial that will evaluate the efficacy and safety of carbetocin nasal spray 3.2 mg administered three times daily. The study will enroll approximately 170 children and adults aged 5 to 30 years with PWS across approximately 36 clinical sites throughout the United States, Canada, and Europe.
The primary efficacy endpoint is the change from baseline to week 12 on the hyperphagia questionnaire for clinical trials (HQ-CT) score, a caregiver assessment for hyperphagia-related behaviors. Participants who complete the Phase 3 study will be eligible to enroll in a long-term, open-label extension study designed to investigate the safety and tolerability of long-term treatment.
Dr. Ponni Subbiah, Senior Vice President, Global Head of Medical Affairs and Chief Medical Officer at Acadia, noted that the trial "will build on previous Phase 3 clinical trial experience, where carbetocin nasal spray 3.2 mg was observed to reduce hyperphagia-related behaviors."
Understanding Prader-Willi Syndrome
PWS affects both males and females and is characterized by dysfunction of the hypothalamus and other brain regions. Beyond hyperphagia, patients may experience altered metabolism, developmental delays, behavioral challenges, and moderate cognitive deficits.
The scientific rationale for carbetocin in PWS relates to the oxytocin system. Individuals with PWS have fewer oxytocin-producing neurons in the brain, and oxytocin deficiency is believed to contribute to hyperphagia. Other symptoms may include high pain tolerance, sleep disturbances, gastrointestinal issues, and respiratory and temperature regulation abnormalities.
About Carbetocin Nasal Spray
Carbetocin nasal spray is an investigational drug with improved properties compared to oxytocin, including an extended half-life and greater specificity for the oxytocin receptor compared to vasopressin receptors. The intranasal formulation provides direct delivery to the brain, reducing systemic exposure and potential side effects.
The drug has received Orphan Drug, Fast Track, and Rare Pediatric Disease designations from the FDA, highlighting the significant unmet need in this patient population.
Acadia acquired worldwide rights to carbetocin nasal spray in June 2022 through its acquisition of Levo Therapeutics.
Patient Recruitment Information
Patients and families interested in the COMPASS PWS study can visit www.CompassPWS.com for more information, including a "Find a Research Site" tool that will be updated as trial sites open. Questions about the study can be directed to Acadia at medicalinformation@acadia-pharm.com.
About Acadia Pharmaceuticals
Acadia Pharmaceuticals has been working in neuroscience for 30 years and has developed approved therapies for Parkinson's disease psychosis and Rett syndrome. The company's clinical development pipeline includes programs for the negative symptoms of schizophrenia, Prader-Willi syndrome, Alzheimer's disease psychosis, and neuropsychiatric symptoms in central nervous system disorders.
