BioPharma, Pharma

Schizophrenia Trial Failure Ends Acadia’s Efforts to Expand Use of Its Flagship Drug

With pimavanserin’s Phase 3 failure in schizophrenia, Acadia Pharmaceuticals said it will no longer run clinical trials for the drug, whose lone approval is for treating psychosis from Parkinson’s disease. The FDA previously rebuffed regulatory submissions for the drug in dementia and Alzheimer’s disease.

brain in hands

An Acadia Pharmaceuticals drug that’s already approved for treating psychosis in Parkinson’s disease patients could not beat a placebo in a pivotal schizophrenia study, spelling the end of efforts to develop a medication the company once envisioned as having potential applications across a range of neurological disorders.

The clinical trial failure announced Tuesday evaluated the drug, pimavanserin, as a treatment for negative symptoms of schizophrenia. The main goal was to show a change in score according to an assessment used to measure the disease’s symptoms. According to the preliminary results, the pimavanserin arm achieved a numerical change in score that was similar to the change reported in a prior Phase 2 study. But San Diego-based Acadia also said the placebo effect in Phase 3 was higher. Consequently, the score change in the Phase 3 trial was not enough to be statistically significant.

Pimavanserin was initially approved in 2016, a regulatory decision that made the drug the first treatment for the hallucinations and delusions experienced by some Parkinson’s patients. In this indication, the once-daily capsule is marketed under the brand name Nuplazid. The Acadia drug is a small molecule designed to bind to 5-HT2A, a serotonin receptor that plays a role in psychosis. Parkinson’s psychosis was just the lead indication for the drug. The company conducted additional clinical trials to support potential label expansion.

In 2021, the FDA rejected Acadia’s application for pimavanserin in dementia-related psychosis, pointing to a lack of statistical significance in some patient subgroups. The following year, FDA turned down an application for the drug as a treatment for psychosis in Alzheimer’s patients, asking the company to conduct another clinical trial. Acadia instead discussed a resubmission based on additional analyses of existing clinical data. That resubmission was also rejected, leading the company to cease efforts to develop the drug for Alzheimer’s psychosis. The latest failure in schizophrenia marks the last time the company will try to expand pimavanserin’s label beyond Parkinson’s psychosis.

“We are disappointed the trial did not meet its primary endpoint given the significant unmet need in patients with negative symptoms of schizophrenia,” Acadia CEO Steve Davis said in a prepared statement. “We will continue to analyze these data with our scientific advisors, but we do not intend to conduct any further clinical trials with pimavanserin.”

Nuplazid accounted for $549.2 million in revenue in 2023, a 6.1% increase over sales of the product in 2022, according to Acadia’s financial reports. The company also has a new contributor to revenue, Daybue. A year ago, this drug became the first FDA-approved treatment for Rett syndrome, a rare genetic neurological disorder. In 2023, Daybue accounted for $177.2 million in sales.

Acadia reported a cash position of $438.9 million at the end of 2023. In addition to supporting commercialization of Nuplazid and Daybue, the capital will also support development of a pipeline of drug candidates in various stages of development for central nervous system disorders and rare diseases. After the wind down of pimavanserin, Acadia’s next most advanced program is ACP-101, a drug in Phase 3 clinical trials for treating the insatiable appetite caused by the rare disease Prader-Willi syndrome. The pipeline also includes ACP-204, a novel molecule that has reached Phase 2 testing in Alzheimer’s disease psychosis.

Photo: Matthew Horwood, Getty Images