Response to Pimavanserin Treatment in Patients With Dementia-related Psychosis: Results From the 12-Week, Open-label Phase of the HARMONY Study

Dementia-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). No therapies are approved in the US to treat DRP. Pimavanserin is a selective serotonin inverse agonist/antagonist at 5-HT2A receptors.

HARMONY was a randomized, placebo-controlled, phase 3 relapse-prevention study in patients with moderate-to-severe psychosis associated with AD, DLB, PDD, VaD, or FTD. Eligible patients entered a 12-week open-label (OL) period where they received pimavanserin 34mg once daily. Response (‚â•30% reduction in Scale for the Assessment of Positive Symptoms Hallucinations+Delusions total score and Clinical Global Impression-Improvement score of much/very much improved) was assessed throughout the OL period. Only patients with a response at both weeks 8 and 12 were eligible to randomize into the double-blind period of the trial.

392 patients were enrolled into the OL period; 41 were ongoing at the time of early study termination. Overall, 61.8% of eligible patients met response criteria and demonstrated sustained response (59.8% AD, 71.2% PDD, 71.4% VaD, 45.5% DLB, 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, Mini-Mental State Examination (MMSE)/dementia severity, or previous drug therapy, with >50% of patients meeting response criteria at week 4 across most subgroups.

During the OL period of HARMONY, a substantial reduction in psychosis symptoms was observed with pimavanserin treatment, irrespective of dementia subtype or baseline MMSE/dementia severity.