5 April 2021 - - US-based pharmaceutical company Acadia Pharmaceuticals Inc. (NASDAQ: ACAD) has received a Complete Response Letter from the US Food and Drug Administration regarding its supplemental New Drug Application for Nuplazid (pimavanserin) for the treatment of hallucinations and delusions associated with dementia-related psychosis, the company said.

The FDA issued a CRL to indicate that they have completed their review of the application and has determined that the application cannot be approved in its present form.

Despite prior agreements with the Division of Psychiatry regarding the pivotal Phase 3 HARMONY study design targeting a broad DRP patient population analyzed as a single group, the Division, in the CRL, 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.

The DRP pivotal HARMONY study met its prespecified primary and secondary endpoints with robust and persuasive clinical and statistical superiority of pimavanserin over placebo, which was a prospectively agreed prerequisite for the DRP indication.

Statistical separation by dementia subgroups and certain minimum numbers of patients with specific subtypes were not among the prespecified requirements.

The Division also said in the CRL that it considers the Phase 2 Alzheimer's disease psychosis study -019, a supportive study in the sNDA filing, to not be adequate and well controlled, citing that it was a single center study with no type I error control of secondary endpoints in which certain protocol deviations occurred.

The company believes these observations impact neither the positive results on the study's primary endpoint, nor the study's overall conclusions of efficacy.

There were no safety issues or concerns raised in the CRL, the company said.

The sNDA submission of pimavanserin for the treatment of hallucinations and delusions associated with DRP was supported by results from the pivotal Phase 3 HARMONY study, which met its primary endpoint, demonstrating that pimavanserin significantly reduced the risk of relapse of psychosis by 2.8 fold compared to placebo (hazard ratio = 0.353; one-sided p=0.0023).

Pimavanserin also met the key secondary endpoint in the study, significantly reducing the risk of discontinuation for any reason by 2.2 fold compared to placebo (hazard ratio = 0.452, one-sided p=0.0024).

The sNDA also included positive efficacy results from two additional placebo-controlled studies, both of which met their respective primary endpoints: the Phase 2 study in patients with Alzheimer's disease psychosis and the Phase 3 study in patients with Parkinson's disease psychosis.

In addition, the sNDA included a large safety database from completed and ongoing studies representing over 1,500 patients with neurodegenerative disease.