Nuplazid Significantly Delays Relapses in Dementia-related Psychosis, Phase 3 Study Shows

Treatment with Nuplazid (pimavanserin) significantly delays time to a psychosis relapse in people with dementia-related disorders such as Alzheimer’s and Parkinson’s diseases, according to results from the ongoing Phase 3 HARMONY study.

Evaluation by an independent data monitoring committee recommended an early stop to this trial based on the treatment’s “robust” efficacy, Acadia Pharmaceuticals, Nuplazid’s manufacturer, announced in a press release. The study’s primary goal — that of a statistically significant longer time to a psychosis relapse — was met in this early analysis.

The findings will be presented by Erin Foff, MD, PhD, Acadia’s clinical director, at the upcoming 12^th Clinical Trials on Alzheimer’s Disease (CTAD) Meeting, which will take place Dec. 4-7 in San Diego. The late-breaking oral presentation will be titled “HARMONY Relapse-Prevention Study: Pimavanserin Significantly Prolongs Time to Relapse of Dementia-Related Psychosis.”

Nuplazid is a selective serotonin inverse agonist that works by binding to serotonin receptors called 5HT2A, which have been associated with several mental health disorders, including psychosis, depression and schizophrenia. However, instead of activating the serotonin signaling cascade, Nuplazid does the opposite, blocking the activity of these receptors.

The U.S. Food and Drug Administration (FDA) approved Nuplazid in 2016 to treat hallucinations and delusions associated with Parkinson’s disease psychosis. The therapy is not approved to treat dementia-related psychosis, schizophrenia, or major depressive disorder.

Following this trial’s success, Acadia plans to meet with the FDA to explore the possibility of filing a supplemental application in 2020. The company wants to request that Nuplazid’s label be expanded to allow its use as a treatment for dementia-related psychosis based in part on the effectiveness seen in HARMONY.

“We look forward to speaking with the FDA about a supplemental new drug application to support pimavanserin for the treatment of dementia-related psychosis,” said Serge Stankovic, MD, MSPH, Acadia’s president. “I want to thank all of the patients, their families, and the investigators for their participation in this important study.”

HARMONY (NCT03325556) is a Phase 3, placebo-controlled trial designed to evaluate the safety and efficacy of Nuplazid as a preventive treatment for delusions and hallucinations associated with dementia-related psychosis in patients with Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease dementia, vascular dementia, and frontotemporal dementia spectrum disorders.

According to an investor report, most of those enrolled in the trial (67%) were Alzheimer’s patients with related dementia and about 15% had Parkinson’s dementia.

The trial included an initial 12-week stabilization period, in which all participants were treated with oral Nuplazid at a dose of 34 mg, once-a-day, until their symptoms of dementia had stabilized.

Following the open-label stabilization period, all patients showing a sustained response to treatment entered the double-blind period of the trial, in which they were randomly assigned to continue treatment with Nuplazid (34 mg or 20 mg daily) or to switch to a placebo for up to 26 weeks (six months) or until they experienced their next psychosis relapse.

The trial’s primary outcome was to assess the time patients remained free of relapses during the double-blind period of the study.

A relapse, or significant disorder worsening, was defined as hospitalization due to dementia-related psychosis, significant deterioration of dementia-related symptoms on clinical scales, or the need to use an off-label antipsychotic medication to treat dementia-related delusions and hallucinations.

“Psychosis adds dramatically to the marked burden that dementia patients already carry and is one of the most challenging-to-manage aspects of the disease for caregivers,” said Jeffrey Cummings, MD, ScD, director emeritus of Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. “With no approved treatment options available today for dementia-related psychosis, the pimavanserin study results represent a meaningful advance that will potentially bring us a much needed therapy for this debilitating disease.”

Nuplazid has been designated by the FDA as a breakthrough therapy for the treatment of dementia-related psychosis.