FDA Subcommittee Votes Against Pimavanserin for Alzheimer Disease Psychosis Therapy

The US Food and Drug Administration (FDA) Psychopharmacologic Drugs Advisory Committee (PDAC) voted 9 to 3 that there is not sufficient evidence pimavanserin is effective in the treatment of hallucinations and delusions associated with Alzheimer disease psychosis (ADP).

In April of 2016, the FDA approved NUPLAZID^®(pimavanserin) for the treatment of hallucinations and delusions associated with Parkinson disease psychosis.

This resubmitted supplemental New Drug Application (sNDA) from Acadia Pharmaceuticals Inc., was the second submission, the first being for an indication for the treatment of dementia-related psychosis. Study ACP-103-019 (045), a relapse prevention study, was the primary source of effectiveness evidence in the original application; Study 019 was designed as a proof-of-concept study and submitted as supporting evidence for the dementia-related psychosis indication.

“For the secondary and relevant exploratory endpoints, none of the between-group comparisons met nominal significance and demonstrated no notable numerical separation (including the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), 21 Cohen-Mansfield Agitation Inventory-Short Form (CMAI-SF) total score, or the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) total score,” the PDAC wrote in the briefing document. “Pimavanserin did not separate from placebo on the NPI-NH PS at Day 64 or Day 85.”

The FDA considers the PDAC’s advice when making decisions on drug applications but is not obliged to follow its recommendations. The FDA plans to review the application on August 4, 2022.

“We continue to believe there is substantial evidence across multiple independent clinical studies and endpoints that support the efficacy of pimavanserin in ADP,” said Steve Davis, chief executive officer, Acadia Pharmaceuticals Inc., in a press release. “There are no FDA approved treatments for this critical public health need and off-label use of multi-receptor acting antipsychotics have demonstrated poor patient outcomes, including worsening of cognition and motor function.”

References

Acadia Pharmaceuticals announces outcome of FDA Advisory Committee for NUPLAZID® (pimavanserin) for the treatment of Alzheimer’s disease psychosis. News Release. Business Wire. June 17, 2022. Accessed June 28, 2022.

FDA Psychopharmacologic Drugs Advisory Committee (PDAC). Pimavanserin for the treatment of hallucinations and delusions associated with Alzheimer’s disease psychosis. Briefing Document. June 17, 2022. Accessed June 28, 2022.