Long-term Nuplazid Safe, Well-tolerated by Parkinson’s Psychosis Patients, Extension Study Shows

Nuplazid (pimavanserin), an approved therapy for treating hallucinations associated with Parkinson’s disease psychosis, is generally safe and well-tolerated in the long run, and may be associated with reduced mortality in this particular patient population, findings from a long-term extension study suggest.

The results were presented at the 2020 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, which was held virtually due to the COVID-19 pandemic. The poster was titled “Long-Term Evaluation of Open-Label Pimavanserin Safety and Tolerability in Parkinson’s Disease Psychosis.”

In addition to the motor symptoms of Parkinson’s disease, some patients with the condition experience psychosis, which causes them to experience hallucinations or delusions that affect their quality of life and increase burdens on their caregivers.

Nuplazid, developed by Acadia Pharmaceuticals, was approved by the U.S. Food and Drug Administration (FDA) in 2016 to treat these symptoms of Parkinson’s disease psychosis. It blocks the signaling of certain serotonin receptors in the nervous system, which have been associated with mental disorders such as depression and epilepsy.

Nuplazid has been deemed safe and well-tolerated across a number of randomized clinical trials, but the oral treatment is designed to be taken daily for extended periods and little is known about its safety and tolerability in the long term.

To address that, Acadia designed an open-label Phase 3 extension trial (NCT00550238) that included Parkinson’s disease psychosis patients who completed two prior randomized, six-week Phase 3 trials (NCT00477672 and NCT00658567) and a prior open-label extension Phase 2 study (NCT01518309).

In total, 459 patients were included in extension study, most of whom were men (61.7%), with an average age of 71.2 years. They are receiving once-daily Nuplazid, at an oral dose of 34 mg (the approved dose), with assessments scheduled at two weeks, one month, and three months after entering the trial, every three months thereafter until 12 months, and every six months in the following years.

The study has been going on for more than 10 years, and researchers now are reporting data after a median of 454 days (about 1.2 years) on treatment. Some of these patients have been on Nuplazid for nearly nine years.

Over the follow-up period, 85.4% of patients experienced at least one adverse event (side effect) related to treatment, with most being mild to moderate in intensity. Serious treatment-related adverse events were reported in 41% of patients, and included pneumonia, urinary tract infection, and hip fracture. In total, 29% of patients discontinued treatment due to an adverse event related to Nuplazid.

Findings also demonstrated that disease symptoms remained stable over time, with scores on the Clinical Global Impression (CGI) severity scale and improvements scale being similar at week 192 on treatment (about 3.5 years) compared to study start.

This also was observed among the 43 patients who responded to Nuplazid during the randomized studies — defined as those with a score of zero on the Scale for the Assessment of Positive Symptoms for Parkinson’s Disease Psychosis at week 6 — whose mean CGI-S scores were similarly maintained over time through 150 weeks (roughly 2.8 years).

Caregiver burden scores, meanwhile, increased progressively from baseline (28.2 points) to week 192 (32.5 points).

To date of the report, 61 patients have died, amounting to a mortality rate of 6.45 deaths per 100 patient-years. This was similar to the mortality rate seen in Parkinson’s patients of the same age across a Medicare database (7.3 per 100 patient-years), but lower than the mortality usually seen in people with Parkinson’s disease psychosis (28.2 per 100 patient-years), the team noted.

Also, no disease origin or adverse events were consistently associated with deaths in these patients.

This was the largest Parkinson’s disease psychosis study in which patients were followed for long periods, but the team noted that its open-label nature, the lack of a control group, and that the inability to follow patients after treatment discontinuation are clear limitations.

Still, they concluded that “long-term study showed pimavanserin treatment to be generally safe and well tolerated. No new or unexpected safety findings were observed.”