For the second time in 16 months, the FDA has turned down Acadia Pharmaceuticals’ bid to expand the approval for its antipsychotic drug, this time for treating psychosis experienced by Alzheimer’s disease patients.
The Acadia drug, Nuplazid, was initially approved for treating psychosis in Parkinson’s disease patients. The drug is the San Diego-based biotech’s only approved product. Acadia has been trying to expand use of the medicine to the treatment of psychosis caused by other neurological conditions. In its announcement of the latest rejection, the company said the FDA recommended the company conduct another clinical trial for Alzheimer’s psychosis.
The FDA signaled its wariness about the Alzheimer’s data last year when Acadia had sought to expand Nuplazid’s approval to dementia-related psychosis. In addition to data for this group of patients, the company’s application included results from two other placebo-controlled studies: a Phase 2 test in Alzheimer’s patients and a Phase 3 study in Parkinson’s patients.
In April 2021, the FDA rejected the Nuplazid application for dementia-related psychosis. The regulator told Acadia that the subgroups lacked evidence to show the drug’s efficacy. The agency also flagged the Alzheimer’s subgroup, telling the company that the study, conducted at a single site, was not adequate and well controlled. The agency also advised the company it would be best to conduct additional clinical studies for each patient subgroup in which it would seek additional approvals.
Acadia did not conduct additional clinical studies. In February, the company resubmitted its Nuplazid application with additional analyses of the data it had. In addition to providing a response to the rejected dementia-related psychosis application, the company also sought an additional approval in Alzheimer’s psychosis.
Complete response letters are not public documents. According to Acadia, the FDA letter said that while the Alzheimer’s study demonstrated a statistically significant treatment effect, there are “limitations in the interpretability” of that study’s results. The agency also told the company that the positive effect of the drug in the dementia-related psychosis study appeared to be driven by the positive results in the Parkinson’s dementia subgroup, a condition that is already included in the current approval of the drug for Parkinson’s patients.
“We are disappointed with this outcome,” CEO Steve Davis said in a prepared statement. “ The treatment of Alzheimer’s disease psychosis continues to be an area of high unmet need, for which there is no approved therapy.”
Nuplazid is a small molecule that’s designed to target 5-HT2A receptors, which are thought play a role in neuropsychiatric disorders. The drug’s 2016 approval covered the treatment of hallucinations and delusions that are associated with Parkinson’s psychosis.
In 2021, Nuplazid generated $484.1 million in sales, according to Acadia’s financial reports. In the first quarter of this year, the company reported $115.4 million in sales, an 8.3% increase compared to the same period in 2021. The company is working to expand its portfolio beyond its flagship drug. Last month, it submitted a new drug application for trofinetide, a drug developed for Rett syndrome, a rare genetic neurodevelopmental disorder that has no FDA-approved treatment.
Acadia is scheduled to release its second quarter financial results after the market close on Monday.
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