Federal health regulators have rejected an application filed by Acadia Pharmaceuticals to expand the use of its blockbuster antipsychotic drug, Nuplazid, highlighting concerns that the medication may not be effective among certain subgroups of dementia patients.
In a Complete Response Letter (CRL) submitted by the U.S. Food and Drug Administration (FDA) on April 5, the agency denied the Acadia Pharmaceuticals application to extend approval of Nuplazid for treatment of hallucinations and delusions associated with other forms of dementia-related psychosis (DRP).
Nuplazid (pimavanserin) is an atypical antipsychotic, which is currently indicated for reduction of hallucinations experienced by Parkinson’s disease patients. The drug was introduced by Acadia Pharmaceuticals in April 2016, after it was approved by the FDA through a fast track “Breakthrough Therapy” process.
Shortly after Nuplazid’s release, the medication brought in about $125 million sales in 2017, and Acadia Pharmaceuticals began a supplemental New Drug Application for Nuplazid seeking approval to market the drug for use among patients with various forms of dementia, including Alzheimer’s.
Following a several year application, in which Acadia Pharmaceuticals submitted results of its required DRP pivotal HARMONY study for labeling and post-marketing requirements, the FDA rejected the label expansion Monday and took issue with the drug’s efficacy.
According to the FDA’s response, the agency’s division of psychiatry found “the trial wasn’t enough to prove the drug’s effectiveness because of a lack of statistical significance in some patient subgroups—including those with Alzheimer’s disease—and the small numbers of patients with certain less common dementia subtypes.”
The FDA further stated the included Phase 2 Alzheimer’s disease psychosis study was inadequate, lacking proper controls to account for certain protocol deviations in Alzheimer’s patients.
The rejection came as a surprise to Acadia Pharmaceuticals, who reportedly stated the results of the FDA’s CRL were “very disappointing” and maintained the HARMONY study met its pre-specified endpoints to prove statistical superiority of pimavanserin over the placebo group.
Acadia Pharmaceuticals was already facing concerns over the potential side effects of Nuplazid, after an alarming number of adverse events and patient deaths were reported, leading to serious questions about whether benefits outweigh the potential health risks and whether a Nuplazid recall may be necessary.
In April 2018, the FDA launched a safety review into Nuplazid problems after receiving 2,236 adverse event reports over the course of its first year on the market, including 244 deaths and signs that the drug may actually worsen hallucinations in some cases.
Since 2016, the FDA has received a total of 6,000 Nuplazid incident reports and 700 deaths, with at least 500 of the fatalities listing Nuplazid as the only suspect medication taken by the patient at the time.
The Institute for Safe Medication Practices (ISMP) issued a warning about Nuplazid safety signals in its November 2017 QuarterWatch report, citing Nuplazid may cause a variety of undisclosed problems including falls, insomnia, nausea, and fatigue.
As a result of the drug makers’ failure to adequately warn about the risks associated with their medication, Nuplazid injury lawyers are evaluating whether users may be entitled to compensation through a product liability lawsuit.