Safety and efficacy of pimavanserin in patients with Lewy body dementia experiencing dementia-related psychosis in the HARMONY study.

BACKGROUND: Pimavanserin is approved by the US Food and Drug Administration for the treatment of hallucinations and delusions associated with Parkinson's disease. We analyzed the effect of pimavanserin on psychosis in patients with Lewy body dementia, including Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), from the phase 3 HARMONY trial. METHODS: This subgroup analysis included patients with PDD or DLB from HARMONY, a previously completed, multicenter, randomized, discontinuation study of pimavanserin for dementia-related psychosis. Patients with moderate to severe psychosis received pimavanserin 34 mg once daily for 12 weeks (open-label treatment). Those who achieved a sustained response at weeks 8 and 12 were randomized to continue treatment with pimavanserin or discontinue treatment and receive placebo for up to 26 weeks in the double-blind period. The primary endpoint was the time to psychosis relapse as defined by prespecified criteria. Safety was evaluated by adverse events; effects on motor symptoms and cognitive abilities were also assessed. RESULTS: Overall, 392 patients were enrolled in HARMONY; 49 patients with PDD and 27 patients with DLB were included in the open-label safety analysis, of whom 46 met response criteria and were randomized to receive pimavanserin (n = 22) or placebo (n = 24) during the double-blind period. Psychosis relapse risk was significantly lower with pimavanserin vs. placebo (hazard ratio, 0.031; 95% CI, 0.010-0.103; 2-sided nominal P < 0.0001). Fewer than 50% of patients experienced an adverse event in either treatment period; pimavanserin did not negatively affect motor or cognitive function. CONCLUSIONS: Psychosis relapse risk was significantly lower with pimavanserin vs. placebo in patients with Lewy body dementia. Pimavanserin was also well tolerated and did not worsen motor or cognitive function. Results should be interpreted cautiously since this study is a post hoc analysis of a previous trial that was not originally designed or powered to draw clinical conclusions based on dementia subgroups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03325556 (registered 18 October 2017).