Pimavanserin well tolerated in older patients with neurodegenerative disease

Pimavanserin therapy was well tolerated in frail adult and older patients with neuropsychiatric symptoms related to neurodegenerative disease (NDD) in a recent study presented at AAIC 2023.

“Most patients with NDD, including Parkinson’s disease, will experience neuropsychiatric symptoms, such as hallucinations and delusions, apathy, and agitation, at some point over the course of their disease,” said the researchers.

“NDD patients include frail adults and the elderly who are highly sensitive to adverse effects associated with antipsychotic use. These patients represent an important population for evaluating the safety profile of pimavanserin to further inform its use in patients with Parkinson’s disease psychosis (PDP),” they noted.

This phase IIIb, double-blind, multicentre, parallel-group study analysed 784 frail, older adult patients (mean age 72.4 years, 57.8 percent female) with neuropsychiatric symptoms related to NDD, including PDP. Participants were randomized to receive either pimavanserin 34 mg once daily or placebo (n=392 in each group) for 8 weeks. The primary endpoint of the study was to assess the safety and tolerability of the treatment, as shown by the occurrence of treatment-emergent adverse events (TEAEs). [AAIC 2023, abstract P3-647]

A total of 730 participants completed the study. However, 54 patients withdrew from the study prematurely due to AEs (n=16), withdrawal of consent (n=11), or other reasons (n=12).

After an 8-week treatment period, the overall incidence of TEAEs was comparable between the treatment groups, with 30.4 percent and 29.3 percent of patients reporting ≥1 TEAE in the pimavanserin and the placebo groups, respectively.

Serious TEAEs occurred in 2.0 percent of patients on pimavanserin and 1.5 percent of those on placebo.

The most common TEAEs reported were urinary tract infection (6.4 percent and 4.1 percent) and headache (2.0 percent and 3.8 percent) in the pimavanserin and placebo groups, respectively.

Similar rates of TEAEs leading to treatment discontinuation were observed between the pimavanserin and placebo groups (2.6 percent vs 2.3 percent). Two deaths in each treatment group occurred within 30 days of the last dose.

Secondary endpoints
At week 8, patients treated with pimavanserin achieved significant improvements in Clinical Global Impression-Improvement (CGI-I) and Sleep Disturbances Inventory (SDI) total scores (MMRM* least square mean [LSM] difference from baseline, -0.2; p=0.0140 [CGI-I] and -0.3; p<0.0001 [SDI]).

The change from baseline in extrapyramidal symptoms and cognition to week 8, as measured by ESRS-A** (-0.5 vs -0.6) and MMSE*** (1.3 vs 1.2), respectively, did not differ significantly between the pimavanserin and placebo groups. This result suggests that “pimavanserin was not associated with cognitive decline or motor dysfunction,” the researchers noted.

“Overall, pimavanserin was well tolerated, with improvement in neuropsychiatric symptoms,” said the researchers.

“Safety data were consistent with the well-characterized safety profile of pimavanserin … These results further add to our knowledge of the safety of pimavanserin for patients with PDP,” they noted.