In December ACADIA Pharmaceuticals presented its top-line results from its Phase 3 clinical trial of pimavanserin in people who had dementia-related psychosis. The results had been eagerly awaited; ACADIA stopped the trial early, having reached met its clinical endpoints.

The study involved 392 participants who had dementia and recent hallucinations or delusions (also known as dementia-related psychosis). The participants’ diagnoses included Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease dementia, vascular dementia, and frontotemporal dementia spectrum disorders.

Starting with a 12-week “open label” phase, all subjects received the study drug, pimavanserin. Those who responded positively to the treatment (61.8%) then entered the next phase of the trial. These individuals were randomly assigned to either continue the study drug or change to a placebo. Called a “double-blind, placebo-controlled” trial, now neither the people in the study nor the researchers knew who was receiving the study drug.

The aim of the trial was to assess differences in ‘time to relapse’ (such as worsening of hallucinations or delusions) of those receiving the study drug compared to placebo. In their press release, ACADIA indicated:

“Pimavanserin met the primary endpoint of the study and was stopped at the pre-planned interim analysis by significantly reducing risk of relapse of psychosis by 2.8 fold compared to placebo (HR = 0.353; one-sided p=0.0023). In addition, pimavanserin met the key secondary endpoint by significantly reducing risk of discontinuation for any reason by 2.2 fold (HR = 0.452; one-sided p=0.0024).”.

In layman terms these findings showed that people were nearly three times less likely to develop psychosis if they were kept on the active drug than being put on the placebo.

Hallucinations and delusions are common symptoms in LBD. Unfortunately, people with LBD are at risk of severe reaction to any antipsychotic medication; reactions may include increased confusion, heavy sedation or worsened parkinsonism. As such, risk versus benefit must be carefully weighed when deciding on treatment options for dementia-related psychosis in LBD.

Todd Graham, LBDA’s Executive Director, stated, “The need for more safe and effective treatments for hallucinations and delusions in LBD cannot be understated. LBDA congratulates ACADIA for taking this issue on for those living with dementia.”

ACADIA reported the following safety data from the HARMONY trial:

“Pimavanserin was well-tolerated over the entire 9-month study duration. Patients receiving pimavanserin treatment had no worsening in cognition, as measured by the Mini-Mental State Examination (MMSE) score, from baseline and no worsening of motor symptoms, as measured by the Extrapyramidal Symptom Rating Scale A-score (ESRS-A), from baseline. In the double-blind period, low rates of adverse events were observed, 41.0% of patients on pimavanserin and 36.6% on placebo.

Discontinuations due to adverse events were low, 2.9% for pimavanserin and 3.6% for placebo. Serious adverse events were also low, 4.8% in the pimavanserin group and 3.6% in the placebo group. One death was reported in the open-label period and one death was reported in the pimavanserin group during the double-blind period. Investigators determined neither death was related to the study drug. Additionally, pimavanserin did not result in clinically significant differences in vital signs, weight, or daytime sedation compared to placebo.”

It is not known yet how many subjects with LBD were enrolled in the trial. Larger LBD-specific studies will be needed to determine safety and effectiveness in this uniquely ‘at-risk’ patient population.