Phase 3 Data Shows Pimavanserin for Schizophrenia is No Better Than Placebo

Acadia Pharmaceuticals Inc. announced on March 11 the Phase 3 ADVANCE-2 trial did not demonstrate pimavanserin had a statistically significant improvement over placebo from baseline to week 26 for the treatment of negative symptoms of schizophrenia. Thus, the study did not meet its primary endpoint.¹

“We are disappointed the trial did not meet its primary endpoint given the significant unmet need in patients with negative symptoms of schizophrenia,” said Steve Davis, Acadia’s Chief Executive Officer, in a press release. “We will continue to analyze these data with our scientific advisors, but we do not intend to conduct any further clinical trials with pimavanserin. We want to thank the patients, their families, and the investigators for their contributions in this important study.”

The study expanded off the successful phase 2 trial, an international, 26-week, randomized, double-blind, placebo-controlled study led by Dragana Bugarski-Kirola, MD,MBA,MSci. Invesitgators assessed the efficacy and safety of pimavanserin in patients with negative symptoms of schizophrenia.²

Here, the study reached its primary endpoint on the NSA-16 total score, compared with placebo (-10.4 vs. -8.5; P = .043). In a post hoc analysis, more than half (53.8%) of the patients receiving 34 mg of pimavanserin showed greater improvement in the NSA-16 score compared to placebo (-11.6 vs. -8.5; unadjusted P = .0065).

However, ADVANCE-2, a double-blind, randomized, placebo-controlled study of 34 mg of pimavanserin did not show positive results.¹ The study included 454 adult patients with negative symptoms of schizophrenia who already had control of positive symptoms with ongoing antipsychotic treatment.

ADVANCE-2 also used the total NSA-16 score to assess negative symptoms, everything from poor socialization to lack of motivation. Compared to placebo, pimavanserin did not display significant improvement from baseline to week 26 on the Negative Symptom Assessment-16 (NSA-16) total score (11.8 vs -11.1 (P = .4825; effect size = 0.07).

Although the study did not reach the primary endpoint, pimavanserin was well-tolerated, only having an adverse event rate of 30.4% compared with 40.3% for participants on placebo.

^References

1. ^{Acadia Pharmaceuticals Announces Top-Line Results from Phase 3 ADVANCE-2 Trial of Pimavanserin in Negative Symptoms of Schizophrenia. Acadia. March 11, 2024. https://acadia.com/media/news-releases/acadia-pharmaceuticals-announces-top-line-results-from-phase-3-advance-2-trial-of-pimavanserin-in-negative-symptoms-of-schizophrenia/. Accessed March 12, 2024.}
2. ^{The Lancet Psychiatry Publishes Results from ADVANCE Study Evaluating Pimavanserin Treatment for Negative Symptoms of Schizophrenia. Acadia. December 1, 2021. https://acadia.com/media/news-releases/the-lancet-psychiatry-publishes-results-from-advance-study-evaluating-pimavanserin-treatment-for-negative-symptoms-of-schizophrenia/. Accessed March 12, 2024.}