Small-Scale Trial of Pimavanserin Highlights Modified Functional Status Questionnaire as Reliable Tool for Parkinson Disease Psychosis

Virgilio G. Evidente, MD

In a first-of-its-kind trial using the Modified Functional Status Questionnaire (mFSQ), findings showed that treatment with pimavanserin (Nuplazid; Acadia) resulted in improvements in patients with Parkinson disease psychosis (PDP) across all mFSQ domains, particularly social activity. In the proof-of-concept study, the mFSQ was significantly correlated with the Schwab and England ADL, further highlighting it as a promising scale for this patient population.¹

A total of 29 patients with PDP entered the 16-week, single-arm, open-label study where they were treated with oral pimavanersin at 34 mg and assessed on different functional domains of activities of daily living (ADL) and function using the mFSQ. In this group of moderately severe PDP, treatment with the therapy resulted in improvements across all mFSQ domains, which included Basic ADL, Intermediate ADL, Psychological Function, Quality of Interaction, and Social Activity.

Coming into the study, the main patient age was 70.2 years, with most patients living at home (96.6%). These patients had psychosis symptoms severe enough to warrant treatment with an antipsychotic agent, a Clinical Global Impressions–Severity (CGI-S) score greater than 4, a Schwab & England ADL Scale score of 40%-80%, and a Mini-Mental State Exam score greater than 21. Presented at the 3rd Annual Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 22-25, 2024, a mixed-effects model for repeated measures was used to estimate least-square mean change in mFSQ domains over the treatment period.

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Led by Virgilio G. Evidente, MD, director of the Movement Disorders Center of Arizona, the largest change seen in pimavanserin-treated patients was on the Social Activity subscale. From baseline to week 16, investigators observed LS mean changes of 8.1 (SE, 2.41; P = .0031; n = 22) on Basic ADL, 7.0 (SE, 3.00; P = .0286; n = 21) in Intermediate ADL, 13.3 (SE, 1.94; P <.0001; n = 22) in Psychological Function, 12.3 (SE, 2.07; P <.0001; n = 22) in Quality of Interaction, and 25.8 (SE, 7.52; P = .0026; n = 18) in Social Activity.

A secondary analysis of the study showed that mFSQ scores were strongly correlated with the Schwab & England ADL patient and caregiver scores, as both scales showed a consistent trend of improvement among patients and caregivers. All told, Pearson’s r values were 0.6 (P <.0001) for the patient’s total score and 0.5 (P <.0001) for the caregivers total score. For context, the Schwab & England ADL estimates the abilities of individuals living with a disease relative to a range of life activities spanning from a bedridden, vegetative state to complete independence of function.

Original results from this phase 4 study were previously published online in Cambridge University Press in April 2023. Of the 29 treated with pimavanserin, 24 (82.8%) completed the open-label study. Treated patients showed significant improvements in LS mean mFSQ score change from baseline to week 12 (11.5 [SE, 2.44]) and week 16 (14.0 [SE, 2.50]; P <.0001). Significant improvements (P <.05) were also observed for all secondary outcomes at week 16, which included Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part 1 (–6.3 [SE, 0.97]) and Part 2 (–2.6 [SE, 0.98]), Clinical Global Impression (CGI)-Severity (–1.5 [SE, 0.25]), CGI-Improvement (1.9 [SE, 0.17]), and Patient Global Impression-Improvement (2.0 [SE, 0.22]) scales.²

In November 2023, Acadia announced a phase 2 trial program assessing ACP-204, an inverse agonist at the 5-HT2A receptor, as a potential treatment for patients with Alzheimer disease psychosis, a condition for which there is no FDA-approved medication. The therapy, which builds upon the learnings of pimavanserin, will be tested in a randomized, double-blind, placebo-controlled study that will enroll approximately 318 patients with AD psychosis and follow them over a 6-week treatment period. 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 2016.³

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REFERENCES
1. Evidente VGH, Chrones L, Revankar R, Doshi D, Abler V, Rashid N. Use of the Modified Functional Status Questionnaire to Assess Functioning in Patients with Parkinson’s Disease Psychosis Treated with Pimavanserin. Presented at: ATMRD Congress; June 22-25, 2024; Washington, DC.
2. Evidente VGH, DeKarske D, Coate B, Naujoks K, Abler V. A 16-week open-label study of the effects of treatment with pimavanserin on activities of daily living in subjects with Parkinson’s disease psychosis. CNS Spectrums. 2023;28(2):239. doi:10.1017/S109285293001700
3. 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 June 24, 2024. https://acadia.com/media/news-releases/acadia-pharmaceuticals-initiates-phase-2-clinical-trial-of-acp-204-for-the-treatment-of-alzheimers-disease-psychosis/