The Food and Drug Administration (FDA) has issued a complete response letter (CRL) to Acadia Pharmaceuticals regarding the supplemental New Drug Application (sNDA) for pimavanserin for the treatment of hallucinations and delusions associated with dementia-related psychosis.
The sNDA submission was supported by data from the pivotal phase 3 HARMONY study (ClinicalTrials.gov: NCT03325556) that compared the efficacy and safety of pimavanserin, an atypical antipsychotic, to placebo for the treatment of hallucinations and delusions in 351 patients with dementia-related psychosis. Findings from the study showed that pimavanserin met the prespecified primary and secondary endpoints.
However, in the CRL, the FDA cited “a lack of statistical significance in some of the subgroups of dementia, and insufficient numbers of patients with certain less common dementia subtypes as lack of substantial evidence of effectiveness to support approval.” According to the Company, the agreed upon study design was meant to target a broad dementia-related psychosis patient population as a single group.
“Over the entire course of the review, the [Division of Psychiatry] did not raise any concerns regarding the agreed upon study design, including the issues raised in the CRL,” said Steve Davis, CEO of Acadia. “We will immediately request a Type A meeting to work with the FDA to address the CRL and determine an expeditious path forward for the approval of pimavanserin in [dementia-related psychosis].”
Additionally, the FDA noted that the phase 2 Alzheimer disease psychosis study -019, which supported the sNDA filing, was not adequate and well controlled. According to the Agency, the single center study did not have “type I error control of secondary endpoints in which certain protocol deviations occurred.” The CRL did not raise any safety issues or concerns.
Pimavanserin is marketed under the trade name Nuplazid® and is currently approved for the treatment of hallucinations and delusions associated with Parkinson disease psychosis.
Acadia Pharmaceuticals receives complete response letter from U.S. FDA for supplemental New Drug Application for pimavanserin for the treatment of hallucinations and delusions associated with dementia-related psychosis. [press release]. San Diego, CA: Acadia Pharmaceuticals Inc.; April 5, 2021.