Top-line results from phase III ADVANCE 2 trial of pimavanserin for the treatment of negative symptoms of schizophrenia

Pimavanserin did not demonstrate a statistically significant improvement over placebo on the study’s primary endpoint, the change from baseline to week 26 on the Negative Symptom Assessment-16 (NSA-16) total score (-11.8 vs. -11.1; p=0.4825; effect size=0.07). The safety and tolerability profile of pimavanserin was consistent with previous clinical trials, showing a low rate of adverse events.

“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. “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.”

ADVANCE-2 was a 26-week double-blind, randomized, placebo-controlled study of 34 milligram pimavanserin in 454 adult patients with predominant negative symptoms of schizophrenia who had achieved control of positive symptoms with their ongoing antipsychotic treatment. ADVANCE-2 used the NSA-16 scale, designed to measure change on the wide range of predominant negative symptoms that patients experience, which looks at 16 different items in five subscales and covers symptoms such as blunted affect, poor socialization and lack of motivation. The change from baseline observed in the pimavanserin arm of ADVANCE-2 was similar to the change from baseline observed at the 34 milligram dose in ADVANCE-1 (-11.8 vs. -11.6); however, the placebo effect in ADVANCE-2 was higher than the placebo effect observed in ADVANCE-1 (-11.1 vs. -8.5).

In ADVANCE-2, pimavanserin was well-tolerated with an adverse event rate of 30.4% compared with 40.3% for the placebo arm.