Motor function in patients with neuropsychiatric manifestations of neurodegenerative disease treated with pimavanserin
Daniel Weintraub1, Erin P. Foff2, Clive Ballard3, Bradley McEvoy2, Bruce Coate2, George Demos2, Ana Berrio2, Brandon Abbs4, James M. Youakim2, Srdjan Stankovic2
1Perelman School of Medicine at the University of Pennsylvania, 2Acadia Pharmaceuticals Inc., 3University of Exeter Medical School, 4Acadia Pharmaceuticals Inc., at the time of this analysis

Evaluate motor function changes in patients with neuropsychiatric symptoms (NPS) of neurodegenerative disease (NDD) treated with pimavanserin.


NPS of NDD, such as dementia-related psychosis (DRP), are commonly treated with off-label antipsychotics. These have substantial safety concerns, including worsening motor function and extrapyramidal symptoms, primarily due to their activity as dopamine receptor-blocking agents. Pimavanserin is a selective serotonin 5-HT2A receptor inverse agonist/antagonist.


Motor function was evaluated using the Unified Parkinson’s Disease Rating Scale Part III (UPDRS) or Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) in 2 double-blind, parallel-group studies (019, 046) and in the HARMONY randomized withdrawal study, which included an open-label period followed by a randomized double-blind period. Patients had neuropsychiatric manifestations of NDD (N=626 receiving pimavanserin), including DRP (N=562 receiving pimavanserin). Motor-related treatment-emergent adverse events (TEAEs) were examined based on 71 Preferred Terms.


In 019, mean (SE) UPDRS change from baseline (CFB) to week 12 was similar for pimavanserin (-1.0 [0.96]; n=41) and placebo (-0.5 [1.20]; n=44). In the HARMONY open-label period, the mean (SE) ESRS-A CFB to week 12 was minimal (-0.7 [0.17]; n=244), with a trend toward improved motor function. During the double-blind period, mean CFB in total ESRS-A was small and similar in the 2 treatment groups at all time points. In the 046 interim analysis, least squares mean ESRS-A CFB to week 8 was similar for pimavanserin (-0.3 [0.37]; n=132) and placebo (-0.6 [0.37]; n=130). In each study, individual motor-related TEAEs in pimavanserin patients were reported at rates ≤2.2%; rates were similar to placebo.


Mean changes in motor function were minimal in pimavanserin-treated patients and were similar to placebo. In pimavanserin-treated patients, motor-related TEAEs were reported infrequently and at similar rates to placebo. Pimavanserin did not have a negative impact on motor function in this aggregated dataset of frail, vulnerable patients.