Interim results from the ongoing Phase 3 HARMONY study show that treatment with Nuplazid (pimavanserin) significantly delays time to a psychosis relapse in patients with dementia-related disorders, such as Parkinson’s and Alzheimer’s disease.
Evaluation by an independent data monitoring committee recommended an early stop to this placebo-controlled 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.
Nuplazid was approved by the U.S. Food and Drug Administration (FDA) to treat hallucinations and delusions associated with Parkinson’s disease psychosis in 2016. The therapy is not approved to treat dementia-related psychosis, schizophrenia, or major depressive disorder.
After closing the study in the coming months, Acadia plans to meet with the FDA to explore the possibility of filing a supplemental application in 2020, requesting 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 are very excited that today’s results bring us one step closer to the potential of offering patients with dementia-related psychosis a critically needed treatment option,” said Serge Stankovic, MD, MSPH, Acadia’s president.
“We look forward to speaking with the FDA about a supplemental new drug application to support pimavanserin for the treatment of dementia-related psychosis,” Stankovic added. “I want to thank all of the patients, their families, and the investigators for their participation in this important study.”
These and other recent HARMONY results will be discussed at the 12th Clinical Trials on Alzheimer’s Disease (CTAD) meeting set for Dec. 4–7, 2019, in San Diego. The oral presentation, “HARMONY Relapse-Prevention Study: Pimavanserin Significantly Prolongs Time to Relapse of Dementia-Related Psychosis,” will be given by Erin Foff, MD, PhD, clinical director at Acadia Pharmaceuticals.
Nuplazid is a selective serotonin inverse agonist that targets serotonin receptors called 5HT2A. These receptors have been associated with mental disorders such as psychosis, depression, schizophrenia, and other neuropsychiatric disorders. Inverse agonists such as Nuplazid bind to the same receptors as agonists, but induce the opposite pharmacological response, blocking the activity of the targeted receptors.
HARMONY (NCT03325556) was designed to explore Nuplazid’s ability to safely and effectively treat delusions and hallucinations associated with dementia-related psychosis across a broad population of patients, and was scheduled to end in August 2020.
It enrolled people with the most common subtypes of dementia, including Alzheimer’s and Parkinson’s disease, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia spectrum disorders, at sites across the U.S., Europe and in Chile.
For an initial 12 weeks, all were treated with Nuplazid at 34 mg once daily until dementia was stable, or with a reduced 20 mg dose if clinically justified within the first four weeks.
After this stabilization period, patients showing a sustained treatment response were then randomly assigned to continue treatment with Nuplazid (34 mg or 20 mg each day) or to switch to placebo for 26 weeks (six months). About 20% failed to show a sustained response during this early period.
All participants were followed through this double-blind period, or until a relapse of psychosis symptoms. 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/or hallucinations.
A “number of these patients” completed the full six months of treatment, as well as the initial three-month stabilization period, showing a sustained response, Acadia said in an investor report. Exact patient numbers were not available, as a rolling enrollment was underway.
The preliminary efficacy analysis revealed that those treated with Nuplazid had significantly longer periods of time without a psychosis relapse compare to the placebo treated group. “The interim analysis results … clearly demonstrates the strong durability of treatment with pimavanserin,” the company said. Analyses are continuing.
Safety was also comparable to what was seen in earlier trials, with no new safety concerns identified.
About 15% of the people in the trial had Parkinson’s dementia; a majority, or about 67%, were Alzheimer’s patients with related dementia.
“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,” Jeffrey Cummings, MD, ScD, director emeritus of Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, said.
The FDA designated Nuplazid a breakthrough therapy for the treatment of Parkinson’s disease psychosis.