Data Support Long-term Efficacy of Nuplazid for Psychosis

Treatment with Nuplazid (pimavanserin) can ease symptoms of Parkinson’s disease psychosis (PDP) for up to 10 weeks, and is generally safe and well-tolerated, according to new clinical trial data.

The findings were published in Parkinsonism and Related Disorders, in the study, “Efficacy results of pimavanserin from a multi-center, open-label extension study in Parkinson’s disease psychosis patients.”

Nuplazid, by Acadia Pharmaceuticals, is an oral medicine that was approved by the U.S. Food and Drug Administration (FDA) as a treatment for PDP in 2016, based on a clinical trial showing that the treatment eased PDP symptoms, relative to a placebo.

More recently, the FDA approved new formulations of the medication that can be taken more easily by some patients, and is considering whether to approve Nuplazid to help treat dementia-related psychosis.

In the new study, a team led by researchers at Acadia reported on results from an open-label extension (OLE) clinical trial (NCT00550238). The trial, which Acadia sponsored, enrolled participants who had received either Nuplazid or a placebo during one of three prior six-week-long double-blinded clinical trials (NCT00477672, NCT00658567, NCT01174004).

In the OLE trial, all participants received 34 mg Nuplazid daily (the approved dosage).

In total, the new study reports on data for 424 trial participants who had been in the OLE for four weeks. The participants’ mean age was 71.2 years, 92.2% were white, and 61.7% were male. The trial was conducted at 114 clinical sites in 14 countries.

The main measure of psychosis symptoms used in the trial was the Scale for the Assessment of Positive Symptoms (SAPS); higher scores on this scale indicate more severe symptoms of psychosis.

Among all participants, SAPS scores decreased by a mean of 1.8 points, from the start of the OLE to four weeks, suggesting that the treatment eased symptoms.

Notably, the decrease in SAPS score was substantially larger — mean decrease of 2.9 points — among participants who originally had been on placebo in the double-blind studies, before they entered into the OLE. More modest improvements also were seen among participants given lower dosages of Nuplazid in the double-blind trials.

The overall change in SAPS score over 10 weeks — six weeks in the double-blind trials, plus four in the OLE — was comparable among all participants, with a mean decrease of about seven points.

“Among those who switched from placebo to 34 mg pimavanserin [Nuplazid] in the OLE study, mean scores improved to the same level as the 34 mg pimavanserin group over the next 4 weeks of the OLE study,” the researchers concluded.

Other assessments of psychotic symptoms, as well as measures of life quality and caregiver burden, generally followed a similar trend, which indicates, “that the effects on psychosis were clinically meaningful to caregivers as well as clinicians,” the researchers wrote.

“Results from a multi-center OLE study, across 14 countries, demonstrate the extended durability of efficacy of Nuplazid for treating hallucinations and delusions associated with PDP, in addition to reinforcing the efficacy seen in the original pivotal trial using the 34 mg dose,” Stuart Isaacson, MD, said in a press release from Acadia. Isaacson is director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida, and co-author of the study.

In the four weeks of the OLE trial, about half of participants reported adverse events (side effects). Most were mild or moderate in intensity. The most common included fall (5.9%), hallucination (3.7%), urinary tract infection (2.8%), insomnia (2.4%), and swelling in the lower legs or hands (2.2%). Seven participants experienced serious adverse events, the most common being pneumonia and other lung problems.

“Nuplazid is a critical first-line therapy for our patients living with PDP, and their caregivers,” Isaacson said.