Nuplazid Shows Sustained Easing of Psychosis in Patients in Phase 3 Trial

Daily use of Nuplazid (pimavanserin) leads to strong and sustained reductions in the frequency and severity of hallucinations and delusions in people with Parkinson’s disease psychosis, according to data from a long-term extension study.

These findings, “Improvement and Durability in SAPS-PD Assessment over 10 Weeks of Pimavanserin Treatment for Parkinson’s Disease Psychosis,” were presented at the at the 2020 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, which was held virtually due to the COVID-19 pandemic.

Nuplazid, marketed by Acadia Pharmaceuticals, is a selective serotonin inverse agonist that works by blocking the activity of serotonin receptors called 5HT2A. These receptors have been associated with several mental health disorders, including psychosis, depression and schizophrenia.

The medication is currently approved in the U.S. to treat hallucinations and delusions associated with Parkinson’s disease psychosis (PDP).

Nuplazid’s approval was supported by findings in several clinical trials, including a completed Phase 3 study (NCT01174004), that assessed its safety and efficacy compared with a placebo in 199 people with Parkinson’s psychosis.

Patients were randomly assigned to either Nuplazid (34 mg) or placebo tablets, both taken once-a-day for six weeks.

Study findings showed that compared to a placebo, Nuplazid reduced the frequency and severity of hallucinations and delusions without worsening patients’ motor symptoms.

All patients who completed this and earlier Nuplazid studies were then invited to enroll in an open-label extension study (NCT00550238) to either continue or start (previous placebo group patients) treatment with Nuplazid for four weeks.

The prospective analysis presented at ASCP was based on data from 171 patients who completed the original Phase 3 trial and entered in its long-term extension. Of these, 148 (87%) completed the extension study.

Findings showed that Nuplazid’s use led to strong and durable reductions in the frequency and severity of hallucinations and delusions, as measured by the Scale for the Assessment of Positive Symptoms – Parkinson’s disease (SAPS-PD), since the beginning of the original study up until the end of its extension study. This scale is a structured patient interview that consists of five domains: hallucinations, delusions, bizarre behavior, positive formal thought disorder, and inappropriate affect. Higher scores indicate more severe psychosis.

Such benefits were seen both in patients who started treatment in the original trial and were given Nuplazid for a total of 10 weeks (mean reduction of 6.86 points), and in those who only started treatment in the extension study and were on the medication for four weeks (mean reduction of 6.28 points).

In people previously given a placebo, SAPS-PD scores decreased by an average of 3.43 points since the beginning of the extension study until its completion one month later. Among those given Nuplazid in the original trial, SAPS-PD scores remained nearly constant over this trial’s four weeks (slight increase of 0.43 points).

Improvements as assessed by the Clinical Global Impression-Severity and Improvement (CGI-S and CGI-I) scales were also seen, particularly in patients who switched from a placebo in the original trial to Nuplazid in the extension study.

Among these patients, nearly half (46.6%) felt they had very much improved or much improved by the second week of the extension study, and more than half (57.1%) reported the same at week four.

Adverse events observed during the extension study were identical to those reported in the original trial. The most common included falls, hallucinations, urinary tract infections, and swelling.

Most adverse events were only mild or moderate in severity. A total of 14 (8.2%) patients had to stop treatment due to side effects.

“Overall, the sustained improvement in the severity of psychotic symptoms was suggested in patients with PDP [Parkinson’s disease psychosis] receiving treatment with pimavanserin 34 mg daily for 10 weeks,” the researchers wrote.

During the meeting, Acadia also presented data on the long-term safety and tolerability of Nuplazid with Parkinson’s patients, and new findings from trials enrolling people with other central nervous system (CNS; the brain and spinal cord) disorders, including major depressive disorder and schizophrenia.

“Our research presentations at ASCP underscore the potential clinical utility of pimavanserin in serious CNS disorders,” Serge Stankovic, MD, MSPH, president of Acadia, said in a press release.

“Pimavanserin has demonstrated the potential to be an important treatment option for patients [with schizophrenia and major depressive disorder and showed promising] long-term safety and tolerability … in Parkinson’s disease psychosis,” Stankovic added.