FDA advisers back Lundbeck and Otsuka's Rexulti in Alzheimer's disease agitation

With an FDA advisory committee recommendation in hand, Lundbeck and Otsuka’s Rexulti is one step closer to locking down a new indication in Alzheimer’s disease related agitation.

In a 9-1 vote on Friday, experts on the FDA's Psychopharmacologic Drugs Advisory Committee and the Peripheral and Central Nervous System Drugs Advisory Committee recommended a favorable benefit-risk profile for the proposed Rexulti use.

Most of the committee members were persuaded by what they viewed as “convincing” data, a reasonable safety profile and high unmet need. If the FDA eventually follows the vote—and it typically does—it would be the first nod for the specific condition.

“I obviously feel that this is an unmet need that we’ve got to address, and I hope this is just the start of it,” patient representative Colette Johnston said during Friday's meeting.

“The data speaks for itself,” added committee member David Weisman, M.D., from the ANA Clinical Research Center.

The one objecting vote was doled out by consumer representative Kim Witczak, who didn’t think that the data presented outweigh the dangers that are typically present in antipsychotic medications. She also expressed concern over how the drug could be marketed, noting that “we need to really keep an eye” on it.

One of the dangers consistent in many antipsychotics, especially in this patient population, is the mortality risk. Across all three phase 3 studies, nine deaths were reported, with eight in Rexulti patients. The FDA in its briefing documents noted that Rexulti’s effect on mortality is “consistent” with the known risk of other antipsychotics in elderly patients with dementia.

In the briefing documents released ahead of the meeting, FDA reviewers pointed to results in two phase 3 studies in which Rexulti proved to reduce agitation over a 12-week period. The agency appeared to back an approval, concluding that Lundbeck and Otsuka provided “substantial evidence” of the drug’s effectiveness.  

Rexulti scored its initial approval in 2015 for schizophrenia and as an add-on treatment for major depressive disorder. The drug carries a black box warning for an increased morality risk in elderly adults with dementia-related psychosis, plus for increased risk of suicidal thoughts and behaviors in patients 24 years and younger who are on an antidepressant.

Last year, the drug raked in 2.85 billion Danish kroner ($405 million) in sales for Lundbeck. In a June 2022 note, SVB Securities analysts said that an Alzheimer’s disease agitation indication could raise Rexulti’s peak sales by $500 million.