FDA Committee to Review Nuplazid in Treating Alzheimer’s Psychosis

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by Patricia Inacio, PhD |

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A U.S. Food and Drug Administration (FDA) advisory committee will host a virtual meeting to review a request to expand the approval of Nuplazid (pimavanserin) to include psychosis due to Alzheimer’s disease dementia.

The FDA’s Psychopharmacologic Drugs Advisory committee meeting on the application recently submitted by Acadia Pharmaceuticals, which developed and markets Nuplazid, is scheduled for June 17. The committee’s decision is expected by Aug. 4.

“We appreciate our ongoing engagement with the FDA and look forward to a productive discussion on the clinical evidence supporting the positive benefit-risk profile for pimavanserin as a treatment for ADP [Alzheimer’s disease psychosis] at the upcoming … meeting,” Steve Davis, CEO of Acadia, said in a press release.

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Acadia submitted a new supplemental new drug application in February after the FDA rejected its first request to expand Nuplazid’s use to a broader category of dementia-related psychosis, a condition often marked by hallucinations and/or delusions. The therapy was approved by the FDA to treat psychosis linked to Parkinson’s disease in 2016.

At the time, the FDA did not note any safety issues related to Nuplazid but raised concerns regarding the Phase 3 HARMONY clinical trial (NCT03325556) that served as the basis for the broad request.

HARMONY enrolled 392 people with common types of dementia-related psychosis, with most patients (76%) having Alzheimer’s-related psychosis. Others included psychosis related to Parkinson’s disease dementia, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.

Almost two-thirds of these people were seen as responders to an initial 12-week lead-in treatment period. These 217 patients were then randomly assigned to continue daily treatment with Nuplazid at 34 mg, or 20 mg for people with tolerability issues, or to a placebo for about six months.

Results showed the risk of a psychosis relapse to be almost three times lower in patients taking Nuplazid.

The oral therapy was also generally well-tolerated, and not associated with common side effects of conventional antipsychotics, including cognitive decline or daytime sleepiness.

FDA concerns included the small number of participants with rarer dementia types, and a failure to show significant benefits in some dementia forms. These issues prompted its decision to not approve Nuplazid for dementia-related psychosis.

Acadia’s February application includes additional HARMONY analyses, as well as results of a Phase 2 trial (NCT02035553) that tested Nuplazid against a placebo for 12 weeks in 181 people with Alzheimer’s-related psychosis.

According to Acadia, 1 in every 3 people with Alzheimer’s experience psychosis.

“The hallucinations and delusions that Alzheimer’s patients endure represent one of the most significant burdens in this community, and one of the leading reasons for long-term care placement,” Davis said. “There are no FDA-approved treatments for this critical public health need.”

Nuplazid works by blocking serotonin signaling in the brain, which is believed to contribute to the development of psychotic symptoms.

“Off-label use of multi-receptor acting antipsychotics with marginal efficacy and significant safety concerns can lead to poor patient outcomes, including worsening of cognition and motor function,” Davis added.