Nuplazid (pimavanserin) is more effective in reducing severe psychotic symptoms — particularly hallucinations and delusions — in Alzheimer’s disease patients than in those with milder symptoms, according to additional Phase 2 clinical trial results.
Patients with neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease-associated dementia, and dementia with Lewy bodies, can develop dementia-related psychosis.
Psychotic symptoms, including delusions and visual hallucinations, are estimated to occur in 25-50% of people with Alzheimer’s disease, and have been associated with faster cognitive and functional decline.
Currently, there is no approved treatment for dementia-related psychosis, and off-label antipsychotic medications currently used to treat Alzheimer’s patients have been associated with a decline in cognition and with serious side effects.
The Phase 2 clinical study (NCT02035553) evaluated the safety and effectiveness of Nuplazid in reducing psychotic symptoms in Alzheimer’s patients with psychosis.
The study enrolled 181 patients over age 50 and living in nursing homes. Participants were randomized to receive two 20 mg tablets per day of either Nuplazid (equivalent of 34 mg free base pimavanserin) or a placebo.
The frequency and severity of psychotic symptoms were assessed using the validated Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) psychosis score (hallucinations and delusions domains).
The results showed that after six weeks of Nuplazid treatment, patients had significantly reduced psychosis, compared with those receiving placebo.
A 30% improvement in the NPI-NH score at six weeks was found in 55.2% of treated patients, compared to 37.4% of those receiving a placebo. This was achieved without negatively affecting cognition. However, no benefit in comparison with placebo was sustained at week 12.
Now, researchers assessed the safety and effectiveness of Nuplazid specifically in the 57 patients who showed more severe psychosis at enrollment (about 30% of all participants). Twenty-seven of them received Nuplazid, 30 received a placebo, and 81% of these patients had both hallucinations and delusions at the beginning of the study.
After six weeks, Nuplazid treatment in this more severe group of patients induced a more than twofold greater reduction in the NPI-NH psychosis score than the one found for all patients receiving Nuplazid in the study. The severity of hallucinations and delusions was significantly decreased in these patients.
This decrease was also found to be three times greater than the one reported in studies evaluating the therapeutic benefits of antipsychotic medication in patients with dementia-related psychosis.
The researchers also found that, at six weeks, 88.9% and 77.8% of patients in the Nuplazid group showed at least a 30% and 50% reduction in psychotic symptoms, respectively.
However, while improvement in psychosis were maintained in the Nuplazid group at 12 weeks, patients receiving placebo showed similar improvements to those receiving Nuplazid from week six to 12, and no significant difference in psychosis improvement was found between the two groups at 12 weeks.
Among patients with more severe psychosis, the frequency of adverse events and serious adverse events was similar between the two groups, and fewer patients receiving Nuplazid (7.1%) stopped treatment, compared to those in the placebo group (10.0%).
The data suggests that Nuplazid is an effective and safe therapy to ease psychotic symptoms in Alzheimer’s patients with psychosis.
“These findings, coupled with the results from other studies of [Nuplazid], suggest a potential role for [Nuplazid] in treating dementia-related psychosis in patients across a range of neuropsychiatric conditions,” Clive Ballard, the study’s first author, said in a press release.
Acadia is currently conducting the multi-center HARMONY Phase 3 trial (NCT03325556) evaluating the efficacy of Nuplazid in preventing a relapse of psychotic symptoms in patients with dementia-related psychosis, including those with possible or probable Alzheimer’s or Parkinson’s. Patient recruitment is ongoing. For more information, visit the webpage here.