The FDA’s post-marketing review concludes a five-month speculation which began when CNN reported the Acadia Pharmaceutical antipsychotic therapy was associated with more than 700 deaths of patients with Parkinson disease since June 2016.
The US Food and Drug Administration’s (FDA) review of post-marketing reports have confirmed that pimavanserin (Nuplazid) is not associated with any new or unexpected safety findings that link the drug to patient deaths and serious adverse events (SAEs).
The FDA’s review concludes a five-month speculation which began when CNN reported the Acadia Pharmaceutical antipsychotic therapy was associated with more than 700 deaths of patients with Parkinson disease (PD) since June 2016. The April 2018 report—which had combined statistics from nonprofit healthcare organization Institute for Safe Medication Practices (ISMP), Acadia’s new drug application, and the FDA’s Adverse Events Reporting System (FAERS) to link 741 SAEs reported as deaths to pimavanserin—was negated by the FDA’s conclusive ruling Thursday.
“After a thorough review, FDA’s conclusion remains unchanged that the drug’s benefits outweigh its risks for patients with hallucinations and delusions of Parkinson’s disease psychosis,” a statement from the FDA read.
Pimavanserin, along with other antipsychotics, carries a Boxed Warning regarding the increased risk of death in elderly patients with dementia-related psychosis. But the FDA had ruled that no findings were inconsistent with the already-established safety profile detailed on the drug label.
That said, the FDA noted potentially concerning prescribing patterns in their investigation, including the association between concomitant use of other antipsychotics or drugs and patient arrhythmia disorders (QT prolongation). They advised that healthcare providers remain aware of the risks already described in the prescribing information, and that none of the other antipsychotic medications are approved for the treatment of PD psychosis like pimavanserin.
The FDA also stated that the high mortality rate and increased age of the average patient with advanced PD was taken into consideration during their investigation—many of these patients also suffer from other medical conditions. Additionally, pimavanserin’s primary distribution is through patient support programs and specialty pharmacy networks, increasing the likelihood of patient deaths being reported to the manufacturer.
In their assessment of FAERS reports that included a patient cause of death, there was no evident pattern that suggested pimavanserin’s fault—many reports to FAERS do not provide sufficient information.
“Overall, the postmarketing data were consistent with the safety data obtained from the premarketing controlled clinical trials of Nuplazid for Parkinson’s disease psychosis,” the FDA stated.
A therapy with a novel mechanism that allows it to behave as a selective inverse agonist of the 5-HT 2A receptor without significant affinity or activity at dopamine receptors, pimavanserin is considered a novel antipsychotic among its drug class. It was approved to treat hallucinations and delusions associated with psychosis experienced by patients, on the strength of a six-week trial involving 199 patients.
In the application trial, the drug showed efficacy in decreasing the frequency and severity of hallucinations and delusions in PD patients without worsening primary motor symptoms, according to the FDA.