Acadia Initiates Phase 2 Study of Investigational Agent ACP-204 in Alzheimer Psychosis

In recent news, Acadia Pharmaceuticals announced a phase 2 trial program assessing ACP-204, an inverse agonist, as a potential treatment for patients with Alzheimer disease (AD) psychosis, a condition for which there is no FDA-approved medication. The initial phase 2 study is part of a larger phase 2/3 program that includes 2 other phase 3 studies of identical design.¹

Randomized, double-blinded, and placebo-controlled in design, the phase 2 study will enroll approximately 318 patients with AD psychosis and follow them over a 6-week treatment period. Patients will receive either 30 or 60 mg of ACP-204 or placebo, with change on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D) subscales total score as the primary end point.

The program will seamlessly transition from phase 2 to phase 3, with each of the planned studies to include 378 patients with AD psychosis. Patients who complete the study will have the option to enter a long-term open-label extension phase.

ACP-204 works primarily as an inverse agonist at the 5-HT2A receptor, building upon the learnings of pimavanserin (Nuplazid), Acadia’s FDA-approved medication indicated for patients with Parkinson disease psychosis. To date, the investigational agent has completed phase 1 development, demonstrating a favorable safety and tolerability profile in the doses to be used in the phase 2 study. Overall, the results supported the agent’s target profile as a potential treatment for AD psychosis.²

READ MORE: Building on Momentum: Overviewing Ongoing Efforts from the Alzheimer’s Association

Pimavanserin, originally approved in tablet form, became the first medication marketed for the treatment of hallucinations and delusions associated with psychosis in patients with PD in 2016. It remains the only approved agent to treat the condition. Most recently, the FDA updated the packaging label for the therapy, restating that the phase 3 study that supported its approval included patients with PD psychosis with or without dementia.³ Although no risk information was changed, the therapy’s boxed warning language was further clarified to include patients with PD psychosis who have dementia.

Acadia further pursued an expanded indication of pimavanserin to include the treatment of AD psychosis but was not successful, as the FDA issued a complete response letter to the company in late 2022.⁴ At the time, the agency noted it could not approve the application as is, and recommended that the company conduct an additional trial in AD psychosis. The supplemental new drug application was supported by data from the phase 2 Study-019 trial (NCT02035553) and the phase 3 HARMONY study (NCT03325556), which assessed the therapy over the course of 43 days and 26 weeks, respectively. HARMONY included 392 patients with various dementia subtypes, including AD, PD dementia, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.

REFERENCES
1. Acadia Pharmaceuticals initiates phase 2 clinical trial of ACP-204 for the treatment of Alzheimer’s disease psychosis. News release. Acadia Pharmaceuticals. November 27, 2023. Accessed November 29, 2023. https://acadia.com/media/news-releases/acadia-pharmaceuticals-initiates-phase-2-clinical-trial-of-acp-204-for-the-treatment-of-alzheimers-disease-psychosis/
2. Acadia Pharmaceuticals reports first quarter 2023 financial results and operating overview. Acadia Pharmaceuticals. News release. May 8, 2023. Accessed November 29, 2023. https://ir.acadia.com/news-releases/news-release-details/acadia-pharmaceuticals-reports-first-quarter-2023-financial
3. Acadia Pharmaceuticals announces label update for Nuplazid (pimavanserin). News release. September 18, 2023. Accessed November 29, 2023. https://acadia.com/media/news-releases/acadia-pharmaceuticals-announces-label-update-for-nuplazid-pimavanserin/
4. Acadia Pharmaceuticals Receives Complete Response Letter from U.S. FDA for Supplemental New Drug Application for Pimavanserin for the Treatment of Hallucinations and Delusions Associated with Alzheimer’s Disease Psychosis. Acadia Pharmaceuticals. August 4, 2022. Accessed November 29, 2023. https://acadia.com/media/news-releases/acadia-pharmaceuticals-receives-complete-response-letter-from-u-s-fda-for-supplemental-new-drug-application-for-pimavanserin-for-the-treatment-of-hallucinations-and-delusions-associated-with-alzheime/