FDA Rejects Nuplazid Application for Treatment of Alzheimer’s Disease Psychosis

The agency said more clinical trials would be required showing clearer results before it could approve Nuplazid to treat Alzheimer’s disease psychosis.

Following thousands of reported side effects from Nuplazid, a blockbuster antipsychotic drug that was fast tracked through the FDA approval process a few years ago, federal health regulators have rejected an application by Acadia Pharmaceuticals to expand use of the drug to treat symptoms of Alzheimer’s disease psychosis.

Nuplazid (pimavanserin) was introduced in April 2016, as a medication to help reduce the frequency and severity of hallucinations experienced by Parkinson’s disease patients.

The drug approved by the U.S. Food and Drug Administration (FDA) through a fast track “Breakthrough Therapy” process, but post-marketing follow up has identified thousands of Nuplazid problems, including at least 700 deaths that may be linked to use of the drug.

While the adverse event reports are not proof Nuplazid caused those deaths and injuries, at least 500 of the fatalities reported to the FDA listed Nuplazid as the only suspect medication taken by the patient at the time.

As a result, a growing number of Nuplazid lawsuits have been filed by individuals who have suffered serious injuries, deaths, or ongoing hallucinations, which claim the drug maker failed to adequately warn about the risks associated with their medication.

Last week, the FDA issued a Complete Response Letter (CRL) to Acadia Pharmaceutical’s supplemental New Drug Application (sNDA), rejecting the manufacturer’s application to approve the drug to treat hallucinations and delusions associated with Alzheimer’s disease psychosis.

According to the FDA’s rejection letter, the agency indicates the positive results in Acadia’s Study 045 were largely driven by a subgroup which included patients being treated for Parkinson’s disease psychosis, which is a condition that has already been approved for use. The FDA further stated that while the drug’s efficacy to treat patients was noted in Acadia’s Study 019, the study lacks interpretability and contains limitations, which create the potential for unknown adverse events in patients.

The rejection mirrors a similar decision by the FDA not to approve Nuplazid for use in treating dementia-related psychosis in April 2021.

The FDA instructed Acadia’s Nuplazid medication in its present form could not be approved for the treatment of Alzheimer’s disease psychosis, and recommended the company to run additional clinical trials.

The rejection came as a surprise to Acadia Pharmaceuticals, who reportedly stated the results of the FDA’s CRL were disappointing, and expressed their gratitude to all of the patients, families and investigator who helped design and run the clinical trials.

Reports of Nuplazid Side Effects

The Institute for Safe Medication Practices (ISMP) issued a warning about Nuplazid safety signals in its November 2017 QuarterWatch report, indicating that the FDA had received 2,236 adverse event reports over the course of its first year on the market, including 244 deaths and signs that the drug may actually worsen hallucinations in some cases.

ISMP later released its QuarterWatch Report in 2019, finding hundreds of reports involving problems with Nuplazid, which suggested federal regulators may have made a mistake when they determined that the antipsychotic drug Nuplazid was safe.