The Food and Drug Administration’s (FDA) Psychopharmacologic Drugs Advisory Committee voted 3 “yes” and 9 “no” on whether the available evidence supports the conclusion that pimavanserin is effective for the treatment of hallucinations and delusions associated with Alzheimer disease (AD) psychosis.
Pimavanserin, an atypical antipsychotic, is currently marketed under the brand name Nuplazid® and is approved for the treatment of hallucinations and delusions associated with Parkinson disease psychosis (PDD). The supplemental New Drug Application (sNDA) for Alzheimer disease psychosis included data from the phase 3 HARMONY (ClinicalTrials.gov Identifier: NCT03325556) and phase 2 Study-019 (ClinicalTrials.gov Identifier: NCT02035553) trials.
In the HARMONY study, the FDA panel noted that the primary endpoint (effect of pimavanserin on time to relapse of psychosis) appeared to be driven primarily by results in the PDD subgroup, though the AD subgroup was the largest in the study. It was unclear whether concomitant use of dopaminergic medication explained the difference between groups. Mixed results and study limitations were also revealed in the post hoc analyses.
Though pimavanserin demonstrated a statistically significant treatment effect vs placebo in Study-019, the FDA panel questioned the clinical meaningfulness of the primary endpoint (change from baseline to day 43 in the Neuropsychiatric Inventory-Nursing Home Version psychosis score) treatment difference (<2 points on a 24-point scale). According to the panel, “the lack of support from the secondary efficacy endpoints and the exploratory analyses that do not show discernable differences at [day 64] or [day 85] raise the question of whether the treatment difference at [day 43] is a chance finding (eg, sudden one-time worsening in the placebo group) and/or about the durability of the effect.”
Although not bound by the committee’s recommendations, the Agency does take them into consideration when making decisions on approval. A Prescription Drug User Fee Act (PDUFA) target date of August 4, 2022 has been set for the application.
ReferencesAcadia Pharmaceuticals announces outcome of FDA advisory committee for Nuplazid® (pimavanserin) for the treatment of Alzheimer’s disease psychosis. News release. Acadia Pharmaceuticals Inc. Accessed June 17, 2022. https://www.businesswire.com/news/home/20220617005539/en/Acadia-Pharmaceuticals-Announces-Outcome-of-FDA-Advisory-Committee-for-NUPLAZID%C2%AE-pimavanserin-for-the-Treatment-of-Alzheimer%E2%80%99s-Disease-PsychosisFDA Briefing Document: Psychopharmacologic Drugs Advisory Committee (PDAC) June 17, 2022. Pimavanserin for the treatment of hallucinations and delusions associated with Alzheimer’s disease psychosis. https://www.fda.gov/media/159249/download