ISMP Report Questions Nuplazid Safety, FDA Approval And Lack Of Warnings

It appears that federal regulators may have made a mistake when they determined that the antipsychotic drug Nuplazid was safe, according to the findings of a new report by a consumer advocacy group.

The Institute for Safe Medication Practices (ISMP) released its QuarterWatch Report (subscription required) this week, looking at FDA adverse events for the second quarter of 2018, including hundreds of reports involving problems with Nuplazid.

Researchers indicate that they “respectfully disagree” with the FDA’s decision to issue a statement in September 2018, which provided safety reassurances about the potential side effects of Nuplazid, indiating that the reassurances were not warranted by the data.

Nuplazid (pimavanserin) is an atypical antipsychotic, which is used to reduce hallucinations experienced by Parkinson’s disease patients. The drug was just introduced by Acadia Pharmaceuticals in April 2016, after it was approved by the FDA through a fast track “Breakthrough Therapy” process. However, an alarming number of Nuplazid problems have been reported by individuals nationwide.

Last year, the FDA reported that its Adverse Events Reporting System (FAERS) had received 5,735 incidents involving problems with Nuplazid since 2016.

Nuplazid side effects have also been linked to at least 712 death reports. While the reports do not necessarily mean that Nuplazid was the cause of the deaths, at least 500 of those fatality reports listed Nuplazid as the only suspect medication the patient was taking.

In response to growing concerns, the FDA issued an updated safety communication in September, indicating that its review found no new or unexpected Nuplazid risks.

“In assessing the reports of deaths, FDA considered that patients with Parkinson’s disease psychosis, for whom Nuplazid is indicated, have a higher mortality (death) rate due to their older age, advanced Parkinson’s disease, and other medical conditions,” the reviewers concluded. “Moreover, Nuplazid is primarily distributed through a patient support program and a specialty pharmacy network, which increases the likelihood that deaths will be reported to the manufacturer.”

ISMP researchers raise seriuos questions about the FDA’s reassurances, indicating that their own review of the FDA’s data found 893 death reports, almost all submitted by the manufacturer.

“But agency safety reviewers said most case reports had so little detail that they could not determine whether or not primavanserin contributed to the patient death,” ISMP researchers note. “On one hand, the patients were already at high risk of death from the underlying advanced Parkinson’s disease, but on the other, reviewers could not tell how many deaths had never been reported.”

The ISMP report also notes that after just two months of use, 45% of Nuplazid users had either died or discontinued using the drug. They also found that a recent large clinical trial showed no benefit to Alzheimer’s patients after 12 weeks, suggesting that the drug carries few actual benefits.

Researchers also questioned the clarity of the existing boxed warning on the drug, and noted that the number of reported deaths now exceeds 1,300, with nearly 40% of those giving no details.

Since the drug was approved the for the treatment of hallucinations and delusions linked to Parkinson’s disease psychosis (PDP), Nuplazid generated about $125 million in sales last year for Acadia Pharmaceuticals.

The ISMP first issued a warning about Nuplazid safety signals in its November 2017 QuarterWatch report, indicating that the FDA had received 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.

Potential side effects of Nuplazid reported to federal health regulators also include falls, insomnia, nausea, and fatigue.