HARMONY: Response to pimavanserin in the 12‐week, open‐label treatment phase

Abstract

AbstractBackgroundDementia‐related psychosis (DRP) is common in patients with Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), vascular dementia (VaD), and frontotemporal dementia (FTD). However, no therapies have been approved. Current guidelines and real‐world practice involve a trial of off‐label antipsychotics when other interventions fail, with assessment of response in an individual patient and taper within 4 months in patients who have responded. Pimavanserin is an inverse agonist/antagonist at the 5‐HT2A receptor and is approved in the U.S. for treating hallucinations and delusions associated with Parkinson’s disease psychosis. The objective of this analysis was to examine the response (≥30% reduction on the SAPS‐H+D Total Score AND a CGI‐I score of 1=very much improved or 2=much improved) to pimavanserin during open‐label treatment of patients with DRP.MethodHARMONY was a placebo‐controlled, randomized, Phase 3, relapse prevention study in patients with dementia (NIA‐AA criteria) and moderate to severe psychosis associated with PDD, DLB, AD, FTD or VaD. Eligible patients who failed brief psychosocial therapy during screening entered into a 12‐week open‐label (OL) period where they received pimavanserin 34 mg once daily. Patients were assessed for response at Weeks 8 and 12. Only patients who demonstrated sustained response (response at both Weeks 8 and 12) were eligible to randomize into the double‐blind portion of the trial. OL response rates and changes in psychotic symptoms were assessed in various subgroups within the study populationResult392 patients were enrolled into the open‐label period; 41 patients were ongoing at the time of early study termination. Overall, 61.8% of patients demonstrated sustained response (59.8% AD, 71.2% PDD, 71.4% VaD, 45.5% DLB, and 50.0% FTD). Mean change in the SAPS scores across the OL period was similar regardless of dementia subtype or baseline characteristics. The response rate was similar regardless of age, dementia severity, or previous drug therapy, with more than 50% patients meeting response criteria at Week 4 across most factors.ConclusionIn this Phase 3 study, during the OL treatment phase, pimavanserin produced a robust reduction in psychosis symptoms, irrespective of most likely clinical diagnosis of dementia subtype or baseline MMSE/dementia severity.