ACADIA Pharmaceuticals Presents Positive Top-line Results from Pivotal Phase 3 HARMONY Trial of Pimavanserin in Patients with Dementia-Related Psychosis at 12th Clinical Trials on Alzheimer’s Disease (CTAD) Meeting - Seite 2
Pimavanserin was well-tolerated over the entire 9-month study duration. Patients receiving pimavanserin treatment had no worsening in cognition, as measured by the Mini-Mental State Examination (MMSE) score, from baseline and no worsening of motor symptoms, as measured by the Extrapyramidal Symptom Rating Scale A-score (ESRS-A), from baseline. In the double-blind period, low rates of adverse events were observed, 41.0% of patients on pimavanserin and 36.6% on placebo. Discontinuations due to adverse events were low, 2.9% for pimavanserin and 3.6% for placebo. Serious adverse events were also low, 4.8% in the pimavanserin group and 3.6% in the placebo group. One death was reported in the open-label period and one death was reported in the pimavanserin group during the double-blind period. Investigators determined neither death was related to the study drug. Additionally, pimavanserin did not result in clinically significant differences in vital signs, weight, or daytime sedation compared to placebo.
ACADIA is planning to meet with the FDA in the first half of 2020 regarding a supplemental NDA submission. The FDA previously granted Breakthrough Therapy Designation for pimavanserin for the treatment of dementia-related psychosis. Currently, no drug is approved by the FDA for the treatment of dementia-related psychosis.
About the HARMONY Study
HARMONY was a Phase 3 study designed to evaluate the efficacy and safety of pimavanserin for the treatment of delusions and hallucinations associated with dementia-related psychosis across a broad population of patients with the most common clinically diagnosed subtypes of dementia including: Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease dementia, vascular dementia, and frontotemporal dementia spectrum disorders.
A total of 392 patients were enrolled in the HARMONY study. The average age of patients in the study was 74.5 years. Patients had an average baseline SAPS-H+D score of 24.4, which is reflective of moderate-to-severe psychosis and an average baseline MMSE score of 16.7, which is consistent with the greatest proportion of enrolled patients having moderate dementia.
The HARMONY study included a 12-week open-label stabilization period during which patients with dementia-related psychosis were treated with pimavanserin 34 mg once daily. Dose reduction to 20 mg once daily was allowed based on tolerability within the first four weeks. Following the 12-week open-label period, patients who met pre-specified criteria for treatment response were then randomized into the double-blind period of the study to continue their pimavanserin dose (34 mg or 20 mg per day) or switched to placebo and followed for up to 26 weeks or until a relapse of psychosis occurred. The primary endpoint in the study was time to relapse in the double-blind period as represented by the Kaplan-Meier curve and the hazard ratio. Pimavanserin met the primary endpoint of the study by significantly reducing the risk of relapse of psychosis by 2.8 fold compared to placebo (HR = 0.353; one-sided p=0.0023).