Acadia Pharmaceuticals is terminating development of its antipsychotic drug pimavanserin, which did not demonstrate a statistically significant improvement over placebo in the late-stage study’s primary endpoint.
Pictured: Man leaning against wall/iStock, KatarzynaBialasiewicz
Acadia Pharmaceuticals on Monday unveiled disappointing topline data from its Phase III ADVANCE-2 trial, demonstrating that its antipsychotic candidate pimavanserin did not achieve its primary efficacy endpoint of control of negative symptoms in patients with schizophrenia.
At 26 weeks, patients treated with pimavanserin saw an 11.8-point drop in scores in the Negative Symptom Assessment-16 scale (NSA-16), a semi-structured interview tool that comprehensively evaluates negative symptoms in schizophrenia. Over the same period, placebo comparators demonstrated an 11.1-point drop in NSA-16 scores.
The effect size was small at 0.07 and while it leaned in favor of pimavanserin, it failed to reach statistical significance.
The San Diego-based biotech has yet to reveal more data from ADVANCE-2, though it noted that pimavanserin’s safety and tolerability profile was consistent with prior trials. Adverse events arose in 30.4% of patients in the pimavanserin arm compared to 40.3% in the placebo group.
Acadia CEO Steve Davis in a statement said that the company is “disappointed” with ADVANCE-2’s findings, especially “given the significant unmet need in patients with negative symptoms of schizophrenia.”
The biotech will continue to analyze the data from ADVANCE-2 “but we do not intend to conduct further clinical trials with pimavanserin,” Davis added.
Pimavanserin is an atypical antipsychotic drug whose mechanism of action has yet to be fully elucidated. The FDA approved the medication in 2016 for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis, for which it is marketed as Nuplazid. Its label carries a black box warning for a higher risk of death in elderly patients with dementia-related psychosis.
Despite this initial regulatory win, the drug has suffered several clinical and regulatory setbacks. In April 2021, the FDA rejected pimanvanserin’s bid for approval in dementia-related psychosis. In August 2022, pimavanserin was again denied approval, this time for hallucinations and delusions associated with Alzheimer’s disease psychosis.
Acadia is also advancing therapies for hyperphagia in Prader-Willi syndrome, Rett Syndrome and Fragile X syndrome. It is also working on another candidate for Alzheimer’s disease psychosis.
Monday’s rejection for pimavanserin comes two weeks after the FDA rejected another potential schizophrenia therapy. Last month, Minerva Neurosciences was handed a Complete Response Letter (CRL), indicating that the regulator was denying approval of its investigational 5-HT2A and σ₂ receptor antagonist roluperidone for schizophrenia with negative symptoms.
According to the CRL, Minerva’s application was insufficient to establish evidence of roluperidone’s effectiveness in the indication. The company is currently reviewing its options and will work with the FDA to determine the best path forward for roluperidone.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
