FDA Issues Complete Response Letter for Nuplazid in Alzheimer’s Psychosis


The FDA has requested Acadia conduct an additional trial of Nuplazid to support an indication in patients with Alzheimer’s disease.

Acadia Pharmaceuticals has received a complete response letter (CRL) from FDA regarding its supplemental new drug application (sNDA) for Nuplazid (pimavanserin) to treat patients with hallucinations and delusions associated with Alzheimer’s disease psychosis.

Steve Davis

Steve Davis

“We are disappointed with this outcome. The treatment of Alzheimer’s disease psychosis continues to be an area of high unmet need, for which there is no approved therapy,” Steve Davis, chief executive officer, said in a press release.

Nuplazid is a selective serotonin inverse agonist and antagonist targeting 5-HT2A receptors. These receptors are thought to play an important role in neuropsychiatric disorders. The FDA approved Nuplazid in April 2016 for the treatment of patients with hallucinations and delusions associated with Parkinson’s disease psychosis.

Regulators indicated that one of the studies submitted showed statistical significance for the Alzheimer’s indication, but they agreed with the June 2022 FDA advisory committee conclusion that the evidence from both trials that were submitted doesn’t support approval of Nuplazid in patients with Alzheimer’s.

Related: FDA Advisory Committee Votes Down Nuplazid in Alzheimer’s Psychosis

Specifically, regulators concluded that there are limitations in the interpretability of Study 019 results. The FDA also stated that the positive treatment effect of Nuplazid on dementia-related psychosis in Study 045 (HARMONY) appeared to be driven by the robustly positive results in the Parkinson’s disease dementia subgroup.

Regulators indicated they don’t believe that Alzheimer’s and Parkinson’s psychosis are closely-related conditions.

The FDA and the advisory committee both recommended that Acadia conduct an additional trial in patients with Alzheimer’s psychosis. Committee chairperson and attending psychiatrist and UPMC Western Psychiatric Hospital said after the committee vote in June 2022 that a randomized controlled trial that incorporates Alzheimer’s blood markers, bigger sample size, better outcome measures would be reasonable to generate strong data to support an indication going forward. He is also professor of radiology and psychiatry at the University of Pittsburgh School of Medicine.

Acadia officials, however, have said they don't plan to conduct another study.

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