Nearly half a year after news reports surfaced about deaths allegedly linked to Nuplazid (pimavanserin) — a therapy for Parkinson’s patients with disease-related psychosis — the U.S. Food and Drug Administration says it could not find any new or unexpected safety concerns with the controversial treatment.
The agency said in a Sept. 20 press release that “after a thorough review, the FDA’s conclusion remains unchanged that the drug’s benefits outweigh its risks for patients with hallucinations and delusions of Parkinson’s disease psychosis.”
“As the only drug currently approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis, Nuplazid is filling an important and previously unmet need,” Doral Fredericks, Acadia’s vice president for U.S. medical affairs, said in a statement emailed to Parkinson’s News Today.
She added that “we remain confident in the efficacy and safety of Nuplazid that supported its approval by the FDA and the reaffirmation the agency has given for the positive benefit-risk profile of Nuplazid in its most recent review.”
In that review, the FDA said it considered the fact that patients with Parkinson’s psychosis are more likely to die in the first place due to their older age, advanced disease, and other medical conditions.
“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,” said the agency, referring to its FDA Adverse Event Reporting System (FAERS). “In FAERS reports that included a cause of death (many reports did not provide sufficient information to assess drug cause and effect), there was no evident pattern to suggest a drug effect.”
It added that “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 recommended dosage is 34 mg, taken orally as two 17 mg tablets once daily, with or without food.
The FDA’s recognition of Nuplazid’s complex safety profile after the medication’s April 2016 approval, the agency said in an April 2018 statement, “led to the inclusion of a Boxed Warning and the addition of other important warnings and precautions in the product labeling, so that healthcare professionals could have the risk/benefit information needed to make prescribing decisions.”
Concern over Nuplazid first surfaced following a CNN report in April. An article on the network’s website cited an analysis by the nonprofit Institute for Safe Medication Practices, which found that FAERS showed a total of 700 deaths — including 500 among Parkinson’s patients in which Nuplazid was the only treatment likely involved — in the nine months following Nuplazid’s June 2016 appearance on the market.
Nuplazid is targeted at treating Parkinson’s psychosis, which affects about 40 percent of the 1 million Americans believed to have the disease. According to CNN, the therapy — Acadia’s only product — generated $125 million in 2017 sales for the company.
The New York-based Michael J. Fox Foundation for Parkinson’s Research posted a bulletin about the FDA’s review on its website but offered no independent comments on Nuplazid.
Steve Davis, Acadia’s president and CEO, said he was “very pleased” with the FDA’s statement, saying in the release that “none of the other antipsychotic medications are approved for the treatment of Parkinson’s disease psychosis.”
Michael S. Okun, MD, medical director of the Parkinson’s Foundation, said neurologists like himself generally steer patients to medications that may reduce hallucinations or delusions associated with Parkinson’s without also aggravating motor symptoms of the disease like hand tremors and rigidity.
“The recent safety information provided by the FDA would suggest that Nuplazid is a reasonable option,” Okun said in an email to Parkinson’s News Today. “However, careful counseling on risks and benefits will be important for every patient. Nuplazid joins quetiapine and clozapine as commonly prescribed drugs for Parkinson psychosis. These drugs are typically chosen by expert clinicians over more traditional dopamine blockers because they have a better chance of suppressing psychosis without worsening motor symptoms.”
Fredericks said Acadia’s development program for Nuplazid represents the largest clinical safety database in Parkinson’s psychosis patients ever conducted.
“We are committed to the safe use of Nuplazid in accordance with the FDA-approved prescribing information,” Fredericks said. She promised that her company will continue helping patients “recognize and report symptoms of Parkinson’s disease psychosis to their healthcare provider in order to determine if Nuplazid might be right for them.”