Alzheimer's disease psychosis (ADP) is a common and serious condition with substantial unmet need for safe and effective treatments. Pimavanserin is approved in the US to treat Parkinson's disease hallucinations and delusions. This post-hoc analysis of randomized, double-blind, placebo-controlled, phase 2 trial of nursing home residents with ADP evaluated the efficacy of pimavanserin by improvements (least squares mean change) in the Neuropsychiatric Inventory-Nursing Home Version Psychosis Score (NPI-NH PS). The clinical significance of the primary endpoint was assessed using responder analyses (>=30% and >=50%); numbers needed to treat (NNT); cumulative response (0-100% improvement); All Patients and Severe Psychosis (NPI-NH PS >= 12) subgroups were evaluated; improvements in hallucinations and delusions by NPI-NH-PS frequency (3 or 4 points) and severity (2 or 3 points); and >=50% responder analysis at earlier timepoints (weeks 2 and 4). Among 345 patients screened, 181 patients were randomized to pimavanserin (n = 90) and placebo (n = 91). Patients were elderly (mean age: 86 years) and frail (baseline mean NPI-NH PS scores of 9.5 and 10 for pimavanserin and placebo, respectively). Pimavanserin significantly improved NPI-NH PS relative to placebo (-3.76 versus -1.93, respectively; p = 0.0451). In responder analyses, pimavanserin demonstrated a significantly greater reduction in NPI-NH PS versus placebo at both the >=30% (p = 0.0159) and >=50% (p = 0.0240) thresholds with NNTs of 6 and 7, respectively. Furthermore, pimavanserin demonstrated significantly earlier reductions in NPI-NH PS compared with placebo for the >=30% (p = 0.0336) and >=50% (p = 0.0044) thresholds. The cumulative response analysis demonstrated significantly greater efficacy of pimavanserin for All Patients (p = 0.052) and Severe Psychosis (p = 0.004), and Severe Patients versus All Patients demonstrated a greater reduction in NPI-NH PS (p = 0.011; effect size = 0.73). Pimavanserin also demonstrated numerically greater improvements for the frequency and severity of delusions and hallucinations. Responder analyses at earlier timepoints demonstrated significantly greater response rates with pimavanserin versus placebo at week 2 (p = 0.016) but not 4 (p = 0.051). These findings support pimavanserin as safe and effective in a population of nursing home resident patients with ADP.

Dr Ballard declares consulting fees from Acadia, AARP, Addex, Biohaven, Eli Lily, Enterin, Exciva, H Lundbeck, Janssen Pharmaceuticals, Novo Nordisk, Orion, Otsuka America Pharm, Sunovion Pharm, Suven, Roche, Axosome, and Biogen; speakers fees from Harvard University; travel fees from AARP and Acadia; and advisory board membership for Acadia, Roche, Novo-Nordisk, AARP, Biogen, and Synexus. DPD declares grants from the NIA and Alzheimer's Association; and consulting fees from Acadia, Eisai, Genentech, Novo Nordisk, Jazz Pharmaceuticals, and Biogen. Dr Cummings declares grants from the National Institute of General Medical Sciences (P20GM109025), the National Institute of Neurological Disorders and Stroke (U01NS093334), the NIA (R01AG053798, P20AG068053, R35AG71476), and the Alzheimer's Disease Drug Discovery Foundation; royalties from the Neuropsychiatric Inventory; consulting fees from AB Science, Acadia, Alkahest, AlphaCognition, ALZPathFinder, Annovis, AriBio, Artery, Avanir, Biogen, Biosplice, Cassava, Cerevel, Clinilabs, Cortexyme, Diadem, EIP Pharma, Eisai, GatehouseBio, GemVax, Genentech, Green Valley, Grifols, Janssen, Karuna, Lexeo, Lilly, Lundbeck, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Ono, Otsuka, PharmacotrophiX, PRODEO, Prothena, ReMYND, Renew, Resverlogix, Roche, Signant Health, Suven, Unlearn AI, Vaxxinity, and VigilNeuro; speakers fees from Eisai; and advisory board or data safety monitoring board membership for Acadia, Biogen, Eisai, Genentech, Green Valley, Karuna, Lilly, Lundbeck, Merck, NervGen, Novo Nordisk, Otsuka, Roche, Signant Health, and Vaxxinity. Dr Tariot declares grants from the National Institute on Aging (NIA; RF1 AG041705, 1UF1AG046150, R01 AG031581, R01 AG055444, P30 AG19610); consulting fees from Acadia, Biogen, Genentech, and Novo Nordisk; speakers fees from Clinical Care and WebMD; travel fees from the Alzheimer's Clinical Trials Consortium Alzheimer's Therapeutic Research Institute, Acadia, Cortexyme, and Gerontological Society of America; advisory board or data safety monitoring board membership for Abbvie, AC Immune, Axsome, BioXcel, Cortexyme, Eisai, Genentech, Eisai, Merck, Otuska & Astex, T3D Therapeutics, and Syneos; shares in Adamas Pharmaceuticals (sold in December 2020); and a contribution to a patent (11/632,747) with the University of Rochester. Drs Pathak and Stankovic and Mr Coate are employees and stockholders in Acadia Pharmacueticals Inc.

NCT02035553

This study was funded by Acadia Pharmaceuticals Inc.

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