ACADIA Pharmaceuticals Inc. announced top-line results from its Phase 3 ENHANCE study, which evaluated pimavanserin as an adjunctive treatment in adult schizophrenia patients with persistent inadequate response to their current antipsychotic therapy. A total of 396 patients with moderate-to-severe psychotic symptoms were randomized to receive either pimavanserin or placebo added to their current antipsychotic treatment. There is currently no FDA-approved adjunctive treatment for schizophrenia patients with inadequate response to existing therapies.
In the study, adding pimavanserin to existing antipsychotic treatment showed a consistent trend in improvement of psychotic symptoms, however the results did not achieve statistical significance on the primary endpoint, the Positive and Negative Syndrome Scale (PANSS) total score (p=0.0940). A positive trend was also observed on the key secondary endpoint, the Clinical Global Impression-Severity (CGI-S) score (p=0.0543). The majority of patients in the study were enrolled in Europe (>80%), in this pre-specified subgroup analysis by region, consistent positive results were observed on both the primary endpoint, PANSS total score (unadjusted p=0.0234), and the key secondary endpoint, CGI-S score (unadjusted p=0.0214).
Notably, in the full analysis set, pimavanserin showed significant improvements on two pre-specified measures of negative symptoms: the secondary endpoint PANSS negative symptoms scale sub-score (unadjusted p=0.0474) and the exploratory endpoint PANSS Marder negative factor score (unadjusted p=0.0362).
“I want to thank all the patients, their families, and the investigators who participated in our ENHANCE study. Unfortunately, we did not achieve a statistically significant reduction in the PANSS total score in this study,” said Serge Stankovic, M.D., M.S.P.H., ACADIA’s President. “We are pleased with the improvement in negative symptoms observed in this study. We look forward to completing our ongoing ADVANCE trial evaluating pimavanserin in schizophrenia patients with predominant negative symptoms.”
Pimavanserin was well-tolerated with similar rates of adverse events between adjunctive pimavanserin (40.4%) and adjunctive placebo (36.9%). Adverse events reported in at least 5% of patients in the pimavanserin group included headache, somnolence, and insomnia. Additionally, the adjunctive use of pimavanserin did not result in clinically significant differences in vital signs, weight, metabolic syndrome, and extrapyramidal symptoms compared to adjunctive placebo. Approximately 88% of pimavanserin and 96% of placebo patients completed the study. 1% of patients in each arm reported serious adverse events. Discontinuations due to adverse events were low, 2.5% for pimavanserin and 0% for placebo.
In addition to the ENHANCE study, the Company is currently evaluating pimavanserin for adjunctive treatment of schizophrenia patients with predominant negative symptoms in the 26-week Phase 2 ADVANCE study. The primary endpoint of the study is change from baseline on the Negative Symptom Assessment-16 total score. Top-line results from this study are expected around year-end 2019. There are currently no FDA-approved therapies for the treatment of the negative symptoms of schizophrenia.