Safety and Efficacy of Pimavanserin in Patients with Parkinson’s Disease Dementia or Dementia With Lewy Bodies Experiencing Dementia-Related Psychosis in HARMONY

Lewy Body Dementia is an umbrella term (including dementia with Lewy Bodies [DLB] and Parkinson’s disease dementia [PDD]), for dementias associated with Lewy bodies or abnormal brain deposits of alpha-synuclein protein. Post-hoc analyses of HARMONY evaluated pimavanserin efficacy and safety in patients with LBD and psychosis. In HARMONY, a phase 3, placebo-controlled, randomized discontinuation study, patients received open-label pimavanserin 34 mg/day for 12-weeks (W). Patients who met response criteria at W8 and 12 vs baseline were randomized 1:1 to continue pimavanserin or receive placebo double-blind for ≤26W. The primary endpoint was time from randomization to psychosis-relapse during double-blind treatment, analyzed via Cox regression model. Safety, motor, (ESRS-A), and cognitive-functions (MMSE) were measured. Among 392 enrolled patients, 76 had PDD or DLB; 46 (60.5%) completed open-label treatment and were randomized (placebo n=24; pimavanserin n=22). At open-label baseline, mean age was 72.8 years. When trial was stopped early for efficacy, 1-pimavanserin and 11-placebo patients met relapse criteria. The risk of psychosis relapse was lower in pimavanserin vs placebo (P < 0.0001). Mean ESRS-A and MMSE changes from open-label baseline to W12 were 1.6 and 0.6, respectively, and similar from double-blind-baseline to W26. Overall < 50% experienced a TEAE in the open-label or double-blind periods (mostly mild-moderate). TEAEs leading to discontinuation occurred in 7 patients during open-label and 3 during double-blind period (2 placebo; 1 pimavanserin). Treatment with pimavanserin reduced risk of psychosis relapse in patients with PDD or DLB, was well-tolerated, and did not worsen motor or cognitive function.