ACP-101 for Prader-Willi syndrome

Last updated Sept. 16 2025, by Margarida Maia, PhD
Fact-checked by Marta Figueiredo, PhD

What is ACP-101 for Prader-Willi syndrome?

ACP-101 is an investigational nasal therapy that Acadia Pharmaceuticals is developing for reducing hyperphagia, or insatiable hunger, in people with Prader-Willi syndrome (PWS).

Infants with PWS often experience initial symptoms such as slow growth and difficulty gaining weight. However, as they age, they typically develop hyperphagia. This can result in excessive weight gain and challenging behaviors, including anger when seeking food or frustration when food is unavailable.

ACP-101 is a nasal spray formulation of carbetocin, a lab-made version of the oxytocin hormone whose production is impaired in the brain of people with PWS. Oxytocin plays a critical role in appetite by sending fullness signals to the brain and helps regulate social and emotional behaviors.

Carbetocin binds to oxytocin receptor proteins more strongly than the natural hormone itself and lasts longer in the body. It has been cleared for use in more than 100 countries, but not the U.S., to prevent postpartum bleeding following cesarean delivery.

By delivering carbetocin directly into the brain through a nasal spray, ACP-101 should ease hyperphagia and its related behaviors, along with other behavioral symptoms in people with PWS.

ACP-101 was originally developed by Levo Therapeutics under the name LV-101. The therapy’s development and commercial rights were transferred to Acadia after it acquired Levo in 2022.

The therapy has received orphan drug, fast track, and rare pediatric disease designations in the U.S. for PWS. All these designations are meant to speed ACP-101’s clinical development and regulatory review.

Therapy snapshot

How will ACP-101 be administered?

ACP-101 is designed to be administered through a nasal spray. In previous clinical trials, the therapy was tested at a dose of 3.2 or 9.6 mg, delivered three times a day. The 3.2 mg dose was subsequently selected for testing in an ongoing Phase 3 trial.

ACP-101 in clinical trials

The safety and efficacy of ACP-101 were initially evaluated against a placebo in a Phase 2 clinical trial (NCT01968187). A total of 37 children with PWS, ages 10-18, received either a dose of 9.6 mg of ACP-101 or a placebo, three times a day via a nasal spray for 14 days. Results showed that, compared with the placebo, ACP-101 significantly reduced hyperphagia and obsessive-compulsive behaviors.

Two ACP-101 doses, 9.6 mg and 3.2 mg, were subsequently tested in an international Phase 3 trial called CARE-PWS (NCT03649477) involving 138 children with PWS, ages 7-18. Data showed that eight weeks, or about two months, of treatment with the 9.6 mg dose was not significantly superior to the placebo at easing hyperphagia-related behaviors or obsessive-compulsive behaviors. This meant the trial failed to meet its main goals. Still, compared with the children on the placebo, those given the 3.2 mg dose showed a significant reduction in:

• hyperphagia-related behaviors
• anxiety and distress
• clinician’s perceived global disease severity

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. That ongoing global Phase 3 study, called COMPASS PWS (NCT06173531), is evaluating 3.2 mg of ACP-101 against a placebo in up to 170 children and adults, ages 5 to 30, with PWS. Participants are receiving their assigned treatment through the nose three times a day for 12 weeks, or about three months.

The main goal is to assess changes in hyperphagia-related behaviors, as measured with the caregiver-reported Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Top-line findings are expected later this year.

Those who complete COMPASS PWS may enroll in an open-label extension study (NCT06420297), in which all will receive ACP-101 for up to 36 months, or three years, to check its long-term safety.

ACP-101 side effects

Adverse events reported with ACP-101 in clinical trials so far were mild or moderate in severity. The most common ones, reported at higher rates than in the placebo group, included:

• flushing
• headache
• diarrhea
• infection of the upper respiratory tract (nose, throat, and airways)
• nasal discomfort
• fever
• fatigue

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