Alarm as FDA fast-tracks first antipsychotic drug for agitation in dementia

In trials, the antipsychotic drug brexpiprazole (Rexulti) failed to offer a clinically significant profit and elevated the chance of loss of life. But the US Meals and Drug Administration (FDA) has quick tracked its approval, making Rexulti the primary antipsychotic for treating agitation in aged sufferers with dementia.

At a price of round $1,400 a month Rexulti’s makers, Otsuka and Lundbeck, are forecasting an extra $1 billion in annual gross sales, however there are critical questions concerning the harm-benefit stability of this drug, writes investigative journalist Robert Whitaker in The BMJ in the present day.

The choice might also reverse years of effort by the US Facilities for Medicare and Medicaid Providers (CMS) to cut back the widespread off-label use of antipsychotics in residential care houses.

Like different antipsychotics, the drug carries a “boxed warning,” FDA’s most critical sort of warning, informing prescribers of elevated danger of loss of life. And within the three pre-approval trials, the FDA concluded that the loss of life charge was 4 occasions increased in these given brexpiprazole in comparison with these given placebo.

On efficacy, the drug confirmed a most 5.3-point enchancment over placebo on a 174-point scale, far in need of the 17 factors thought of to be clinically necessary.

“The small advantages don’t outweigh critical security issues,” Public Citizen well being researcher Nina Zeldes instructed the FDA’s Advisory Committee previous to the approval. “Like different antipsychotics, it is a drug that may kill sufferers with out offering a significant profit.”

Professor Lon Schneider on the Keck Faculty of Drugs of the College of Southern California famous that the brexpiprazole outcomes mirrored the outcomes from earlier trials of antipsychotics in Alzheimer’s sufferers, but none of those different antipsychotics has been authorized for treating behavioral signs in aged sufferers with dementia.

Schneider says the FDA has a “decrease commonplace of approval” in the present day than it did 20 years in the past, a theme echoed by Zeldes, who stated, “We’re very disenchanted that the FDA authorized this extra label indication for brexpiprazole on such weak information. The FDA has set a harmful precedent concerning the information it might require for future drug approvals for this weak affected person group.”

In a vote, 9 of the FDA committee’s 10 members believed there was enough information to determine a inhabitants in whom advantages outweighed the drug’s dangers. However even amongst these voting sure, a number of advisors expressed concern about its use in sufferers with gentle signs. Some confused the necessity for individualized risk-benefit analysis in collaboration with sufferers’ households.

The chair of the advisory committee, Rajesh Narendran, didn’t reply to a number of requests for an interview to reply questions raised by this approval, whereas a spokesperson for the FDA’s Middle for Drug Analysis and Analysis said that “as a consequence of conflicting schedules and competing priorities,” the FDA can be unable to reply.

Whitaker notes that various affected person advocacy teams, such because the Alliance for Getting older Analysis, Leaders Interact on Alzheimer’s Analysis (LEAD), and Us Towards Alzheimer’s, urged the FDA to approve brexpiprazole.

This public help is fueled, partly, by industrial pursuits, he writes.

LEAD, for example, is a “coalition of greater than 200 organizations” that features, amongst its members, Otsuka and different pharmaceutical firms, whereas the Alliance for Getting older Analysis, which lists 31 companions, receives funding from Otsuka and different pharmaceutical firms for “non-branded well being training and advocacy on neuropsychiatric signs of dementia.”

Erick Turner, a former FDA reviewer and professor of psychiatry at Oregon Well being & Science College, stated that clinicians’ responses to the approval will possible range based on their present beliefs about prescribing antipsychotics to Alzheimer’s sufferers.

He added, “On the subject of promoting, I do assume it is going to come right down to KOLs [key opinion leaders] and drug reps ‘educating’ clinicians.”

Whitaker writes that if Otsuka’s presentation to the drug advisory committee is any information, the speaking level it is going to use to market brexpiprazole is that it’s a lot safer than different antipsychotics, although that favorable security comparability was constructed into Otsuka’s design of section III trials.

Such advertising and marketing efforts will possible be at odds with ongoing efforts by the CMS. “Antipsychotic drugs are particularly harmful among the many nursing residence inhabitants due to their doubtlessly devastating unintended effects, together with loss of life,” a CMS spokesperson stated. “We can’t converse to the hypothetical future use of brexpiprazole; nonetheless, CMS will proceed its efforts to cut back the prescribing of pointless antipsychotics in nursing houses.”