Pimavanserin safety in adult and elderly patients with neuropsychiatric symptoms related to neurodegenerative disease: An open-label extension study

Background An 8-week, phase 3b, randomized, placebo-controlled trial demonstrated that pimavanserin, a selective 5HT 2A inverse agonist, is generally well tolerated in elderly patients with neuropsychiatric symptoms related to neurodegenerative disease (NDD). Objective This open-label extension (OLE) study assessed the long-term safety and tolerability of pimavanserin. Methods Patients from the antecedent double-blind (DB) trial who were treated with oral pimavanserin (34 mg/day) or placebo were enrolled. The safety analysis population included all patients who received ≥1 dose of pimavanserin. The primary endpoint was treatment-emergent adverse events (TEAEs). Exploratory endpoints included change from baseline in Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A), Mini-Mental State Examination (MMSE), Clinical Global Impression-Severity (CGI-S), EuroQoL 5-Dimension 5-Level (EQ-5D-5L), and Sleep Disorders Inventory (SDI) scores. Results Patients (N = 595; mean age, 72.2 years) received pimavanserin treatment (mean exposure, 312.4 days). Most patients (95.3%) had dementia (68.7% of whom had Alzheimer's disease), and 70.6% were concomitantly treated with anti-dementia drugs. TEAEs occurred in 238 (40.0%) patients, and 37 (6.2%) had a serious TEAE; 1 (0.2%) was pimavanserin-related. TEAEs resulted in treatment discontinuation in 39 (6.6%) patients. Fatal TEAEs occurred in 11 (1.8%) patients (none considered related to pimavanserin). The mean (standard error) change from DB baseline to OLE Week 52 in MMSE, ESRS-A, CGI-S, EQ-5D-5L, and SDI scores was +0.9 (0.21), −0.3 (0.22), −1.0 (0.05), + 10.7 (0.87), and −0.9 (0.07), respectively. No patients reported suicidal behavior. Conclusions Pimavanserin was generally well tolerated in frail older adults and elderly patients with neuropsychiatric symptoms related to NDD for up to 52 weeks of treatment.