Pimavanserin Effective in Parkinson's Psychosis

Emma Hitt, PhD

November 29, 2012

Pimavanserin has demonstrated antipsychotic effects in acceptable safety and tolerability in a trial of patients with Parkinson's disease psychosis, topline results phase 3 results show.

Pimavanserin, manufactured by Acadia, is a novel, first-in-class nondopaminergic agent that selectively blocks serotonin 5-HT2A receptors and is intended to be taken orally once a day.

Pimavanserin was evaluated in a randomized phase 3 trial called the -020 Study. Patients received 40 mg of pimavanserin or placebo once daily for 6 weeks, following a 2-week screening period that included brief psychosocial therapy. Patients also received their existing Parkinson's treatments throughout the study. A total of 185 patients with Parkinson's disease psychosis were included in the efficacy analysis.

The trial met its primary endpoint by demonstrating antipsychotic efficacy; the 9-item SAPS-PD scale, adapted from the hallucinations and delusions domains of the Scale for the Assessment of Positive Symptoms, was significantly improved with pimavanserin compared with placebo, when comparing mean change from baseline to day 43 (–2.73 for placebo and –5.79 for pimavanserin; P = .001).

Secondary endpoints included motoric tolerability as measured by using parts II and III of the Unified Parkinson's Disease Rating Scale, for which pimavanserin also demonstrated significant benefit. Significant improvements were also seen on the Clinical Global Impression Improvement scale (P = .001).

Improvements were also observed in several exploratory measures, including nighttime sleep, daytime wakefulness, and caregiver burden.

The most common adverse events, which were generally mild to moderate, were urinary tract infection (11.7% placebo vs 13.5% pimavanserin) and falls (8.5% placebo vs 10.6% pimavanserin). In addition, 90% of the patients who completed the clinical phase of this trial and who were considered likely to benefit from continued treatment elected to participate in an extension study of pimavanserin.

"These data represent an unprecedented advance for Parkinson's patients who suffer from the psychosis frequently associated with this disease," said Jeffrey Cummings, MD, ScD, director of the Cleveland Clinic Lou Ruvo Center for Brain Health, Ohio, in the company release.

"Among Parkinson's patients, psychosis is the leading cause of institutionalization and dramatically increases the risk of mortality. Neurologists have limited options to treat this serious disorder, and off-label use of current antipsychotics is linked to increased risk of death and serious adverse events, as well as loss of motor control," he said. "The results of this study suggest that a selective, non-dopaminergic-based therapy has the potential to transform the treatment landscape for patients with this debilitating disorder."

"These significant and consistent top-line results are a strong validation of the optimized study design used in this trial," said Roger G. Mills, MD, Acadia's executive vice president of development, stated in a company written release. "Encouragingly, benefits of pimavanserin were seen by patients, caregivers and investigators, as well as the independent raters. Following the successful outcome of this pivotal Phase III trial, we will continue our ongoing preparations for a confirmatory pivotal Phase III trial, the -021 Study, using the same trial design."