Nuplazid Resubmitted for FDA Approval for Psychosis in Alzheimer’s
Acadia Pharmaceuticals has resubmitted an application to the U.S. Food and Drug Administration (FDA) seeking approval of Nuplazid (pimavanserin) for hallucinations and delusions associated with psychosis in Alzheimer’s disease.
The announcement from Acadia comes less than a year after the FDA rejected the company’s original application for Nuplazid to treat the broader category of dementia-related psychosis. In its response, the FDA did not note any safety issues related to Nuplazid, but raised concerns related to the Phase 3 clinical trial HARMONY that served as the basis for Acadia’s application.
HARMONY (NCT03325556) enrolled 392 people with the most common types of dementia-related psychosis. About three-quarters of the participants had Alzheimer’s-related psychosis, while the remainder had other conditions such as Parkinson’s disease dementia, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.
About two-thirds of participants responded to Nuplazid during a 12-week lead-in period, and these participants were randomized to continue taking Nuplazid (34 per day, or 20 mg in those with tolerability issues), or a placebo, for about half a year. Results indicated overall that Nuplazid reduced the risk of a psychosis relapse by nearly three times. Treated patients were significantly less likely to leave the study for any reason.
The FDA highlighted a lack of significant benefits seen in some dementia forms in the trial, as well as the small number of participants with less common disease types, as major factors in deciding not to approve Nuplazid for dementia-related psychosis last year.
Acadia’s newly submitted supplemental new drug application includes additional analyses from HARMONY, as well as a Phase 2 trial (NCT02035553) that tested Nuplazid against a placebo for 12 weeks in 181 people with Alzheimer’s-related psychosis. Results from the Phase 2 study indicated that Nuplazid decreased psychosis symptoms after six weeks of treatment, but results were not sustained at 12 weeks.
Psychosis is defined by hallucinations — sensing something that does not exist — and/or delusions, which are fixed beliefs with no basis in reality. Nearly one out of every three people with Alzheimer’s experiences psychosis, according to Acadia, and there currently is no approved therapy for psychosis related to Alzheimer’s.
Nuplazid is designed to block serotonin signaling in the brain, which is thought to contribute to the development of psychotic symptoms. The therapy is approved by the FDA to treat psychosis related to Parkinson’s disease.