Pimavanserin, a selective serotonin inverse agonist/antagonist, is FDA-approved to treat hallucinations and delusions associated with Parkinson’s disease (PD) psychosis. This treatment is also being assessed in patients with dementia-related psychosis, for which there are no FDA-approved treatments.
According to results of the phase III HARMONY study, pimavanserin significantly reduced the risk of relapse of psychosis compared with placebo. The data were presented at the 13th Clinical Trials on Alzheimer’s Disease Congress 2020.
Researchersevaluated the relationship between exposure and time to relapse in patients with dementia-related psychosis treated with pimavanserin. HARMONY is a relapse-prevention study that included patients with moderate-to-severe psychosis associated with Alzheimer’s disease, PD, dementia with Lewy bodies, vascular dementia, or frontotemporal dementia.
In the 12-week open-label period, 351 patients received pimavanserin 34 mg orally daily, with flexible dosing (20 mg) up to week four based on tolerability. A total of 217 patients (61.8%) with sustained response were randomized into the 26-week double-blind period where they continued pimavanserin or switched to placebo. A post-hoc analysis was conducted to evaluate time to relapse in patients who completed the open-label period on pimavanserin 34 mg.
The study was stopped early for superior efficacy when a prespecified interim analysis revealed that pimavanserin was associated with a greater than 2.8-fold reduced risk of relapse compared with placebo (hazard ratio [HR], 0.353; 95% confidence interval [CI], 0.172-0.727; one-sided P=0.0023) in the double-blind period.
In a subgroup analysis of 182 patients who completed the open-label period on pimavanserin 34 mg, the researchers observed that continuing pimavanserin reduced the risk of relapse by greater than 3.4-fold compared with placebo (HR, 0.293; 95% CI, 0.135-0.634; one-sided P=0.0009).
An exposure-response model used 18,640 daily records collected from 185 patients throughout the double-blind period; the model observed that higher pimavanserin exposure was associated with a higher probability of being relapse-free. No covariates (including demographics, dementia subtype, baseline Scale for the Assessment of Positive Symptoms Hallucinations and Delusions score, or antidementia medication) statistically significantly impacted relapse risk.
In a safety assessment, urinary tract infection (UTI) was the most common adverse event, occurring in 5.1% of patients receiving pimavanserin in the open-label period, 6.7% of patients receiving pimavanserin in the double-blind period, and 3.6% placebo in the double-blind study.
“Findings from these analyses support the efficacy of pimavanserin 34 mg as a potential treatment for dementia-related psychosis,” the researchers concluded.
The study was funded by Acadia Pharmaceuticals Inc.
Presentation: OC17 Relationship between pimavanserin exposure and psychosis relapse in patients with dementia-related psychosis: clinical results and modeling analysis from the phase 3 HARMONY study. Presented at the 13th Clinical Trials on Alzheimer’s Disease Congress 2020, Nov. 4-7, 2020.