SILVER SPRING, Md. — During research trials, brexpiprazole, the antipsychotic drug available under the brand name Rexulti, did not show a clinically significant benefit and actually increased a user’s risk of death. Still, the U.S. Food and Drug Administration (FDA) has fast-tracked its approval, making Rexulti the first antipsychotic for treating agitated elderly dementia patients.
At a steep $1,400 per month, drugmaker Otsuka and Lundbeck are forecasting an additional $1 billion in sales. However, there are some serious concerns to consider, drug researchers say.
Similar to other antipsychotics, Rexulti has a “boxed warning,” which is the FDA’s most serious type of warning. It lets prescribers know that the drug increases a patient’s risk of death. In three pre-approved trials, the FDA found that the death rate was four times greater among those taking Rexulti compared to a placebo.
“The small benefits do not outweigh serious safety concerns,” Public Citizen health researcher Nina Zeldes told the FDA’s Advisory Committee prior to the drug’s approval, according to a media release. “Like other antipsychotics, this is a drug that can kill patients without providing a meaningful benefit.”
Professor Lon Schneider at the Keck School of Medicine of the University of Southern California explains that the brexpiprazole outcomes were similar to the results from earlier trials of antipsychotics in Alzheimer’s patients, yet none of those other drugs received approval for treating behavioral issues among elderly dementia patients.
Schneider adds that the FDA has a “lower standard of approval” today than it did two decades ago, which Zeldes agrees with.
“We are very disappointed that the FDA approved this additional label indication for brexpiprazole on such weak data. The FDA has set a dangerous precedent about the data it may require for future drug approvals for this vulnerable patient group,” Zeldes says.
During a vote, nine of the 10 FDA committee members believed there was enough data showing that the benefits outweigh the risks for people who would use this drug. Still, even among the majority vote, many advisors expressed concern about patients using the drug with only mild symptoms. Some even encouraged individualized risk-benefit analysis and collaboration with the families of patients.
Rajesh Narendran, the advisory committee chair, has not responded to multiple requests for an interview to answer questions about the drug’s approval. An FDA spokesperson from the Center for Drug Evaluation and Research stated that “due to conflicting schedules and competing priorities,” the FDA couldn’t provide a response.
Investigative journalist Robert Whitaker says that several patient advocacy groups like the Alliance for Aging Research, Leaders Engage on Alzheimer’s Research (LEAD), and Us Against Alzheimer’s, urged the FDA to move forward with brexpiprazole. Researchers note much of the support is being driven by commercial interests. The Alliance for Aging Research, which lists 31 partners, receives funding from Otsuka and other companies for “non-branded health education and advocacy on neuropsychiatric symptoms of dementia.”
Erick Turner, a former FDA reviewer and professor of psychiatry at Oregon Health & Science University, says that how clinicians choose to respond to this approval will likely be different, depending on where their beliefs on prescribing antipsychotics for Alzheimer’s patients currently stand.
“On the topic of marketing, I do think it will come down to KOLs [key opinion leaders] and drug reps ‘educating’ clinicians,” Turner says.
The U.S. Centers for Medicare and Medicaid Services (CMS) has worked tirelessly over the years to lower the rampant off-label use of antipsychotics in residential care homes, and this decision could undo many of their efforts.
“Antipsychotic medications are especially dangerous among the nursing home population because of their potentially devastating side effects, including death,” a CMS spokesperson says. “We cannot speak to the hypothetical future use of brexpiprazole; however, CMS will continue its efforts to reduce the prescribing of unnecessary antipsychotics in nursing homes.”
The findings are published in The BMJ.