CRL cites lack of substantial evidence of efficacy needed for approval.
The US Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Acadia Pharmaceuticals regarding their supplemental New Drug Application (sNDA) for pimavanserin for the treatment of hallucinations and delusions in patients with dementia-related psychosis (DRP). The FDA indicated the application cannot be approved in its current state.
The CRL cited the lack of substantial evidence of effectiveness needed for approval—specifically, lack of statistical significance in some of the subgroups of dementia and insufficient numbers of patients with less common forms of dementia.
“Acadia stands behind the robustly positive results from the pivotal Phase 3 HARMONY study and the prospectively agreed trial design and criteria for establishing efficacy in DRP. Over the entire course of the review, the Division did not raise any concerns regarding the agreed upon study design, including the issues raised in the CRL,” said Steve Davis, Chief Executive Officer 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 DRP.”1
Type A meetings are considered “immediately necessary for an otherwise stalled drug development program to proceed,” according to the FDA website.2
Prior agreements with the FDA Division of Psychiatry regarding the pivotal phase 3 HARMONY study design concluded the intent was to target a broad DRP patient population analyzed as a single group. Prespecified requirements did not include statistical separation by dementia subgroups and minimum numbers of patients with specific subtypes.
The CRL also stated that the phase 2 Alzheimer disease psychosis study -019, a supportive study included in the sNDA filing, was inadequate and not well controlled.3 Reasoning for this belief included that it was a single center study, and there was no type I error control of secondary endpoints in which protocol deviations took place. Despite this, Acadia believes there is no impact on the positive results, nor on the study’s overall efficacy.
1. Acadia Pharmaceuticals. Acadia Pharmaceuticals receives Complete Response Letter from US FDA for supplemental New Drug Application for pimavanserin for the treatment of hallucinations and delusions associated with dementia-related psychosis. News release. April 5, 2021. https://www.businesswire.com/news/home/20210405005229/en/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
2. US Food and Drug Administration. Type A Meetings. Accessed April 7, 2021. https://www.accessdata.fda.gov/cder/sb-navigate/topic3/topic3/da_01_03_0090.htm
3. Park B. FDA rejects pimavanserin sNDA for dementia-related psychosis. MPR. April 5, 2021. https://www.empr.com/home/news/drugs-in-the-pipeline/fda-rejects-pimavanserin-snda-for-dementia-related-psychosis/