ACADIA Announces Pimavanserin Meets Primary and Key Secondary Endpoints in Pivotal Phase III Parkinson’s Disease …

SAN DIEGO--(BUSINESS WIRE)--

ACADIA Pharmaceuticals Inc. (ACAD) today announced successful top-line results from its pivotal Phase III trial evaluating the efficacy, tolerability and safety of pimavanserin in patients with Parkinsons disease psychosis (PDP). Pimavanserin is ACADIAs proprietary, non-dopaminergic product candidate that selectively blocks serotonin 5-HT2A receptors. Pimavanserin met the primary endpoint in the Phase III trial by demonstrating highly significant antipsychotic efficacy as measured using the 9-item SAPS-PD scale (p=0.001). Pimavanserin also met the key secondary endpoint for motoric tolerability as measured using Parts II and III of the Unified Parkinsons Disease Rating Scale, or UPDRS. These results were further supported by a highly significant improvement in the secondary efficacy measure, the Clinical Global Impression Improvement, or CGI-I, scale (p=0.001). In addition, clinical benefits were observed in all exploratory efficacy measures with significant improvements in nighttime sleep, daytime wakefulness and caregiver burden. Consistent with previous studies, pimavanserin was safe and well tolerated in this Phase III trial.

These data represent an unprecedented advance for Parkinsons patients who suffer from the psychosis frequently associated with this disease, said Jeffrey Cummings, M.D., Sc.D., Director of the Cleveland Clinic Lou Ruvo Center for Brain Health. Among Parkinsons 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. 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.

Primary Endpoint

The primary endpoint of the trial was antipsychotic efficacy as measured using the SAPS-PD, a 9-item scale adapted from the hallucinations and delusions domains of the Scale for the Assessment of Positive Symptoms, by comparing the mean change from baseline to day 43 for pimavanserin versus placebo. SAPS-PD assessments were performed by blinded, independent centralized raters. The pimavanserin arm demonstrated a robust 5.79 point improvement in psychosis at day 43 compared to a 2.73 point improvement for placebo, representing a highly significant and clinically meaningful treatment difference of 3.06 points on SAPS-PD (p=0.001).

Note: mixed model repeated measures (MMRM) method was applied in the primary analysis of the intent-to-treat (ITT) population. The significance test was based on least-square mean change from baseline for each arm using a 2-sided beta = 0.05.

Key Secondary Endpoint

The key secondary endpoint of the trial evaluated motoric tolerability and functional outcome using Parts II and III of the UPDRS. The objective of this secondary endpoint was to demonstrate that pimavanserin could achieve its antipsychotic effects without worsening motor function as compared to placebo in PDP patients. A pre-specified, non-inferiority analysis was used to compare the mean change from baseline to day 43 for pimavanserin versus placebo using a two-sided 95 percent confidence interval (CI) for the treatment difference. Motoric improvements were seen in both the pimavanserin and placebo arms and the CI associated with the treatment difference did not exceed a pre-specified margin of 5 points for clinically relevant change, confirming that pimavanserin met this key secondary endpoint and did not worsen motor function in PDP patients.

Secondary and Exploratory Efficacy Measures

Excerpt from:
ACADIA Announces Pimavanserin Meets Primary and Key Secondary Endpoints in Pivotal Phase III Parkinson’s Disease ...