Pimavanserin: New Positive Study Results

Negative symptoms of schizophrenia are associated with higher overall morbidity and decreased functioning. These study results offer hope.

Promising results come from phase 2 ADVANCE study.1 ADVANCE—an international, 26-week, randomized, double-blind, placebo-controlled study—evaluated the efficacy and safety of adjunctive pimavanserin treatment in outpatients with moderate-to-severe predominant negative symptoms of schizophrenia who had achieved control of positive symptoms with their ongoing antipsychotic treatment. Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors.

“Negative symptoms of schizophrenia are associated with higher overall morbidity and decreased functioning, and there are no approved treatments,” said Dragana Bugarski-Kirola, MD, MBA, MSci, Vice President of Clinical Development for Acadia Pharmaceuticals, which supported the trial.2 “These findings lend confidence in our continued evaluation of pimavanserin for the treatment of negative symptoms of schizophrenia. We look forward to sharing results of the ongoing, similarly-designed, phase 3 ADVANCE-2 study, evaluating pimavanserin 34 mg in patients with predominant negative symptoms of schizophrenia.”

ADVANCE met its primary endpoint. Pimavanserin saw significant improvement from baseline to week 26 on the Negative Symptoms Assessment-16 (NSA-16) total score, compared with placebo (-10.4 vs. -8.5; p=0.043). In a post hoc analysis, 53.8% of patients who received the highest pimavanserin dose of 34 mg saw greater improvement in the NSA-16 total score compared to placebo.

Pimavanserin was well-tolerated with high completion rates of approximately 86% in both the pimavanserin and placebo treatment groups through 26 weeks. No clinically significant differences in vital signs, weight, metabolic syndrome, or extrapyramidal symptoms were observed in the pimavanserin group compared to placebo.

“The clinically and statistically significant improvement in negative symptoms of schizophrenia with pimavanserin as an adjunctive treatment with other antipsychotics, combined with the observed favorable tolerability profile, suggest pimavanserin may offer a promising approach in treating negative symptoms of schizophrenia, a severe and difficult condition to treat and significant area of unmet need for patients,” said one of the study’s coauthors, Henry Nasrallah, MD, Professor-Emeritus of psychiatry & behavioral neuroscience at the University of Cincinnati College of Medicine.2

Reference

1. Bugarski-Kirola D, Arango C, Fava M et al. Pimavanserin for negative symptoms of schizophrenia: results from the ADVANCE phase 2 randomised, placebo-controlled trial in North America and Europe. Lancet Psychiatry. November 30, 2021. Accessed December 1, 2021. https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(21)00386-2/fulltext

2. Acadia Pharmaceuticals. The Lancet Psychiatry publishes results from ADVANCE study evaluating pimavanserin treatment for negative symptoms of schizophrenia. News release. December 1, 2021. https://ir.acadia-pharm.com/news-releases/news-release-details/lancet-psychiatry-publishes-results-advance-study-evaluating