The regulatory agency has set prescription drug user fee act action date of April 3, 2021, for the Acadia Pharmaceuticals product.
Acadia Pharmaceuticals has announced that the FDA has accepted its supplemental new drug application (sNDA) for pimavanserin (Nuplazid) for the treatment of hallucinations and delusions associated with dementia-related psychosis (DRP).1
The sNDA is supported by the results of the phase 3 HARMONY study (NCT03325556), in which pimavanserin met the primary end point, demonstrating a significant reduction in the risk of relapse of psychosis by 2.8-fold compared to placebo (hazard ratio [HR], 0.353; one-sided P = .0023). Data from the phase 2 (-019) study in patients with Alzheimer disease (AD) psychosis and the phase 3 (-20) study in patients with Parkinson disease (PD) psychosis, both of which also met their primary end points, also attributed to the sNDA.
The FDA has set a prescription drug user fee act (PDUFA) date of April 3, 2021, for pimavanserin. Steve Davis, chief executive officer, Acadia, said in a statement, “If approved, Nuplazid would be the first therapy indicated for the treatment of hallucinations and delusions associational with dementia-related psychosis. We look forward to potentially bringing this important treatment advancement to patients, caregivers and physicians.”
In addition to meeting primary end point, the drug was well tolerated and was not associated with a decline in cognition as measured by Mini-Mental State Examination scores or onset or worsening of extrapyramidal symptoms. Overall, 41% of patients taking pimavanserin experienced adverse events (AEs) compared with 36.6% on placebo. Discontinuations occurred in 2.9% of pimavanserin-treated patients and 3.6% in the placebo group.2
HARMONY, a double-blind, placebo-controlled trial, contained 392 patients (mean age, 74.5 years) and evaluated the safety and efficacy of pimavanserin for the treatment of hallucinations and delusions associated with dementia-related psychosis in patients with various dementia subtypes, including AD, PD dementia, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.
Patients were initially enrolled in an open-label stabilization period where they received 34 mg pimavanserin once daily for 12 weeks. Ultimately 61.8% of patients met the sustained treatment response criteria at week 8 and 12 and thus proceeded to the double-blind period. Patients then were randomly assigned to receive either 34 mg or 20 mg daily pimavanserin or placebo for up to 26 weeks or until relapse occurred. The trial was originally halted in September 2019 after an interim efficacy analysis identified a statistically significant effect on DRP.3
The drug, a selective serotonin inverse agonist and antagonist preferentially targeting 5HT2A receptors, was approved for the treatment of hallucinations and delusions associated with PD psychosis by the FDA in April 2016. It was later granted breakthrough therapy designation for the treatment of hallucinations and delusions associated with DRP in October 2017.
1. Acadia Pharmaceuticals announces US FDA accepted for filing the supplemental new drug application for Nuplazid (pimavanserin) for the treatment of hallucinations and delusions associated with dementia-related psychosis [news release]. San Diego, CA. Acadia Pharmaceuticals. Published online July 20, 2020. Accessed July 22, 2020. ir.acadia-pharm.com/news-releases/news-release-details/acadia-pharmaceuticals-announces-us-fda-accepted-filing?field_nir_news_date_value%5Bmin%5D=
2. Acadia Pharmaceuticals submits supplemental new drug application to U.S. FDA for Nuplazid® (pimavanserin) for the treatment of hallucinations and delusions associated with dementia-related psychosis [news release] San Diego, CA. Acadia Pharmaceuticals. Published online June 15, 2020. Accessed July 22, 2020. https://ir.acadia-pharm.com/news-releases/news-release-details/acadia-pharmaceuticals-submits-supplemental-new-drug-application
3. Acadia Pharmaceuticals announces pivotal phase 3 HARMONY trial stopped early for positive efficacy as pimavanserin meets the primary endpoint in patients with dementia-related psychosis [news release]. San Diego, CA. Acadia Pharmaceuticals. Published online September 9, 2019. Accessed July 22, 2020. https://biospace.com/article/releases/acadia-pharmaceuticals-announces-pivotal-phase-3-harmony-trial-stopped-early-for-positive-efficacy-as-pimavanserin-meets-the-primary-endpoint-in-patients-with-dementia-related-psychosis/