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Pimavanserin (Nuplazid) treatment both induced remission and prevented post-remission relapse of dementia-related psychosis, according to findings of the drugmaker-sponsored .

During an initial single-arm phase lasting 12 weeks in 392 patients with moderate-to-severe psychosis, about 62% responded to treatment with pimavanserin at 34 mg daily and sustained a treatment response, reported Erin Foff, MD, PhD, of manufacturer Acadia Pharmaceuticals in Princeton, New Jersey, during the virtual Psych Congress 2020.

At week 12, these responders -- who achieved at least 30% reduction in total Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions score as well as a Clinical Global Impressions-Improvement score of "much improvement" or "very much improved" -- were then randomized 1:1 in a 26-week double-blind period to either continue pimavanserin or placebo.

During this double-blind period, remission rates in the pimavanserin group were about one-third those seen with placebo (HR 0.353, 95% CI 0.172-0.727, P=0.0023), meeting the trial's primary endpoint.

"Consequently, this study was stopped early due to superior efficacy," Foff pointed out during a virtual presentation of the poster.

The double-blind period included 95 individuals on pimavanserin compared with 99 on placebo. During this time, 28.3% of those on placebo experienced a relapse in psychosis symptoms versus 12.6% of those on pimavanserin.

Additionally, pimavanserin significantly reduced the risk of treatment discontinuation due to any cause (HR 0.452, 95% CI 0.261-0.785, P=0.0024). A total of 38.4% of those on placebo discontinued treatment for any reason compared with 22.1% of those on pimavanserin.

Treatment was also generally well-tolerated in responders. During the initial open-label period, a total of 36.2% of patients on pimavanserin experienced treatment-emergent adverse events -- 7.7% lead to discontinuation and 5% considered serious. The most common events reported were urinary tract infection (5%) and constipation (2.6%). And during the double-blind period, 41% of those on pimavanserin experienced at least one adverse event versus 36.6% of those on placebo. The most common events during this phase of the trial included headache and urinary tract infection.

During both study periods, there was no negative impact on cognition reported. There was also no decline in Mini-Mental State Examination for participants who were exposed to pimavanserin treatment for the entire nine month study period.

The international trial included a mix of patients with mild, moderate, or severe dementia due to Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease dementia, vascular dementia, and frontotemporal dementia spectrum disorders. All participants also had moderate-to-severe psychosis at baseline.

A selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, pimavanserin was first approved in 2016 for hallucinations and delusions associated with Parkinson's disease psychosis. Based on the HARMONY findings, Acadia has requested approval for the indication of dementia-related psychosis, which is now under FDA review.

"No therapies are currently approved in the United States to treat this condition," Foff noted, adding that "off-label use of typical and atypical psychotics is associated with variable efficacy and significant side effects in dementia patients."

Acadia is also evaluating pimavanserin as an add-on therapy in major depression and schizophrenia; positive phase II data for the latter were presented earlier at the Psych Congress.