Topline Phase 3 Results for Pimavanserin in Dementia-Related Psychosis

Megan Brooks

December 05, 2019

Pimavanserin (Nuplazid, Acadia Pharmaceuticals) is promising in the treatment of dementia-related psychosis, topline results of the phase 3 HARMONY study show. The results were presented today at the 12th Clinical Trials on Alzheimer's Disease (CTAD) meeting in San Diego, California.

Pimavanserin met the primary endpoint of the study and was stopped at the preplanned interim analysis by significantly reducing risk of relapse of psychosis by 2.8-fold compared with placebo (hazard ratio [HR], 0.353; one-sided P = .0023), Acadia Pharmaceuticals said in a news release.

Pimavanserin also met the key secondary endpoint by significantly reducing risk of discontinuation for any reason by 2.2-fold (HR, 0.452; one-sided P = .0024).

"The results presented today are an important advance for patients and caregivers who struggle with the burden of dementia-related psychosis where no approved treatment is currently available," Jeffrey Cummings, MD, director emeritus of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Nevada, said in the release.

"Reducing the risk of relapse of psychotic symptoms by this magnitude is an important and meaningful outcome as these are serious events which could lead to poor patient outcomes and a significant increase in caregiver burden and distress," said Cummings.

Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, which are thought to play an important role in psychosis, schizophrenia, depression, and other neuropsychiatric disorders.

The HARMONY study was a double-blind, placebo-controlled, relapse prevention study involving 392 patients with dementia-related psychosis. The study included a 12-week open-label pimavanserin treatment period prior to the randomization period of the study.

In this open-label treatment period, 62% of eligible patients met prespecified criteria for pimavanserin treatment response at both week 8 and week 12 and were then randomly assigned into the double-blind period of the study.

For patients in the open-label treatment period, change from baseline to week 8 and week 12 on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions score improved by 63% and 75%, respectively.

Pimavanserin was well tolerated, with no worsening in cognition or motor symptoms from baseline, the company said.

"The HARMONY study was designed to answer three very important questions," Acadia President Serge Stankovic, MD, said in the release.

"First, in the 12-week open-label period, pimavanserin treatment showed a meaningful reduction of the symptoms and stabilization of psychosis across all of the five clinically diagnosed subtypes evaluated. Second, in the 26-week double-blind period, patients on pimavanserin had a nearly three-fold reduction of risk of relapse compared to patients on placebo. And third, pimavanserin was well-tolerated by elderly patients with dementia-related psychosis," Stankovic said.

The company plans to meet with the US Food and Drug Administration (FDA) in the first half of 2020 regarding a supplemental new drug application submission.

The FDA previously granted Breakthrough Therapy designation for pimavanserin for the treatment of dementia-related psychosis. Currently, no drug is specifically approved for this indication.

As previously reported by Medscape Medical News, the FDA approved pimavanserin for the treatment of hallucinations and delusions associated with psychosis in Parkinson’s disease in 2016.

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