Top-line Phase 3 trial data on ACP-101 for PWS expected this year
Acadia nasal therapy being tested in patients as treatment for hyperphagia
Thanks to strong enrollment in a Phase 3 clinical trial of Acadia Pharmaceuticals’ ACP-101 — an experimental nasal spray of carbetocin for treating hyperphagia in Prader-Willi syndrome (PWS) — the company announced that it now expects to have top-line data later this year.
That trial, COMPASS PWS (NCT06173531), is testing the therapy candidate in an estimated 170 people with the rare genetic disease. Hyperphagia, or uncontrollable hunger, is PWS’ hallmark symptom, and is linked to obesity and food-seeking behaviors.
If the study’s results are positive, Acadia said it plans to file an application with the U.S. Food and Drug Administration (FDA), by early 2026, seeking ACP-101’s approval in PWS.
“As we look ahead, we’re excited to share that we now expect the topline results from our COMPASS PWS Phase 3 study of ACP-101 early in the fourth quarter [last three months] of 2025,” Catherine Owen Adams, Acadia’s CEO, said in a company press release reporting on financial results from the first three months of this year. “2025 is off to a strong start for Acadia.”
Trial data originally not expected until next year
Launched in late 2023, the COMPASS PWS study is still recruiting children and adults, ages 5 to 30, at most of its locations across the U.S., Canada, and Europe. Study sites are still enrolling in France, Germany, Spain, and the U.K., as well as in North America.
The trial’s main goal is to test how well ACP-101 eases hyperphagia-related behaviors compared with a placebo after about three months. Top-line data were previously expected by mid-2026, but now are expected to be available this year, potentially in September or October, per the company.
In infancy, symptoms of PWS include weak muscle tone, slow growth, and failure to thrive. In early childhood, an uncontrollable hunger begins, often leading to excess weight and even obesity. This hyperphagia can also cause challenging behaviors, like anger when trying to obtain food or frustration when food is unavailable.
The active ingredient in ACP-101 (formerly called LV-101) is carbetocin, a lab-made form of oxytocin. This hormone is involved in behaviors related to emotions and appetite. Children and adults with PWS have low levels of oxytocin, which can contribute to poor emotional control and overeating.
The nasal spray formulation of ACP-101 is designed to deliver carbetocin directly to the brain, helping to reduce the risk of unwanted side effects among patients. Because carbetocin binds strongly to oxytocin receptor proteins, it is expected to help compensate for the hormone’s low levels, easing hyperphagia-related behaviors.
The therapy has received orphan drug, fast track, and rare pediatric disease designations from the FDA for the treatment of PWS. All these statuses are meant to speed ACP-101’s clinical development and regulatory review.
FDA had recommended that additional study be conducted
To date, Vykat XR (diazoxide choline) is the only approved therapy in the U.S. for treating hyperphagia in children and adults with PWS.
ACP-101 was originally developed by Levo Therapeutics, which Acadia acquired in June 2022. Per that deal, Acadia now has worldwide rights to continue to develop the treatment, and market it should it be approved.
Levo had previously filed an application with the FDA for ACP-101’s approval. That submission was based on results from the now-completed proof-of-concept Phase 2 Study 114 (NCT01968187), and the larger, confirmatory Phase 3 CARE-PWS trial (NCT03649477), which also is complete.
While the CARE-PWS study failed to meet its main goal of showing that the higher ACP-101 dose (9.6 mg) significantly eased hyperphagia-related behaviors, significant effects were observed with the lower, 3.2 mg dose.
However, the FDA rejected the application in early 2022 after an advisory committee voted 12-1 against it, saying the evidence was not strong enough to support approval. The agency recommended that another Phase 3 trial be conducted to confirm the beneficial effects of the lower dose, even though the therapy appeared to be safe and well tolerated.
As part of the COMPASS PWS study, patients diagnosed with PWS and experiencing hyperphagia are being randomly assigned to receive either a 3.2 mg dose of ACP-101 or a placebo, inhaled through the nose three times a day for 12 weeks, or about three months.
The main goal is to watch for changes from the study’s start to week 12 in the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score, a caregiver-reported assessment of hyperphagia-related behaviors. In the HQ-CT, higher scores indicate more severe hyperphagia.
Patients who complete COMPASS PWS’ placebo-controlled portion 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 assess the therapy’s long-term effects.
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