New Acadia trial testing carbetocin nasal spray to treat insatiable hunger in PWS

Data, if positive, will support new FDA application for therapy's approval

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Acadia Pharmaceuticals has launched a Phase 3 clinical trial testing the safety and efficacy of ACP-101, an experimental carbetocin nasal spray, for the treatment of hyperphagia, or insatiable hunger, in people with Prader-Willi syndrome (PWS).

The pivotal trial, dubbed COMPASS PWS, is expected to enroll up to 170 children and adults, ages 5 to 30, with hyperphagia, according to a company press release. It will be held at more than 20 study sites across the U.S. and Canada.

ACP-101 was originally developed under the name LV-101 by Levo Therapeutics, which was bought by Acadia in June 2022. With the buy, Acadia acquired the global rights to continue to develop the medication, and market it should it be approved in the future.

Levo previously had submitted a regulatory application to the U.S. Food and Drug Administration (FDA) seeking approval of the carbetocin nasal spray. That application was supported by data from a Phase 2 trial (NCT01968187), and from CARE-PWS (NCT03649477) — a Phase 3 study in which a 3.2 mg dose, but not a higher 9.6 mg dose, significantly reduced hyperphagia in children with PWS.

The FDA rejected the application in January 2022 after all but one member of an advisory committee voted that the available evidence was not enough to support the therapy’s effectiveness. In its response letter to Levo, the FDA said that an additional trial was needed to confirm the nasal spray’s efficacy, despite it appearing to be safe and well tolerated.

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No Substantial Evidence of LV-101 Nasal Spray’s Efficacy, FDA Committee Votes

New Phase 3 trial to focus on 3.2 mg dose of carbetocin nasal spray

The new Acadia-sponsored trial, which will further evaluate the therapy’s 3.2 mg dose, was designed based on feedback from the agency during a meeting earlier this year.

If positive, the COMPASS PWS data will be used to support the filing of a new application seeking the therapy’s approval by the FDA.

“The launch of the Phase 3 COMPASS PWS trial will build on previous Phase 3 clinical trial experience, where carbetocin nasal spray 3.2 mg was observed to reduce hyperphagia-related behaviors,” said Ponni Subbiah, MD, Acadia’s senior vice president.

“We look forward to working with the Prader-Willi community and clinical research sites as we continue to advance the ACP-101 clinical development program for those living with this debilitating syndrome and their families,” added Subbiah, also Acadia’s global head of medical affairs and chief medical officer.

The launch of the Phase 3 COMPASS PWS trial will build on previous Phase 3 clinical trial experience, where carbetocin nasal spray 3.2 mg was observed to reduce hyperphagia-related behaviors.

ACP-101 contains carbetocin, a lab-made form of oxytocin, a hormone involved in behaviors related to emotions and appetite. People with PWS have low oxytocin levels, leading to symptoms such as obesity, behavioral challenges, and bone damage.

The nasal spray formulation of ACP-101 is designed to deliver carbetocin directly into the brain, thus reducing the potential for unwanted side effects. The medication, which was given three times a day prior to meals in previous trials, is expected to ease hyperphagia, which has been linked to obesity and anxiety in some PWS patients.

“There is no FDA-approved treatment for hyperphagia in PWS, which presents serious challenges for those living with this condition and their families,” said Shawn McCandless, MD, an investigator of the COMPASS PWS trial.

“Essentially all [PWS patients] 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,” added McCandless, who is chair of genetics and metabolism at Children’s Hospital Colorado.

In the COMPASS PWS trial, children and adults with a diagnosis of PWS and insatiable hunger will be randomly assigned to receive either 3.2 mg of ACP-101 or a placebo, three times daily for 12 weeks, or about three months.

The study’s main efficacy goal is a change on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score, a caregiver assessment for hyperphagia-related behaviors in which a reduction in score indicates improvement.

Participants completing the trial will be eligible to continue in an open-label extension study, in which all will receive ACP-101 for up to three years. That extension study will assess the therapy’s long-term effects.

Carbetocin nasal spray has been granted orphan drug, fast track, and rare pediatric disease designations by the FDA, all of which are meant to speed its clinical development and regulatory review.