Rexulti backed for Alzheimer’s agitation by FDA adcomm

Otsuka and Lundbeck’s antidepressant Rexulti should be approved to treat Alzheimer’s disease-related agitation (AAD), according to FDA advisors – a move that could unlock a sizeable new market for the drug.

The advisory committee voted by nine to one that Rexulti (brexpiprazole) had been shown to offer efficacy in AAD that outweighed its side effects, and that the two drugmakers had shown it was possible to identify patients who would benefit from the treatment.

The only dissenting voice on the panel, from consumer representative Kim Witczak, said the data was not strong enough, given the safety data with the atypical antipsychotic drug, which has been approved by the FDA to treat schizophrenia and major depressive disorder (MDD) since 2015.

Briefing documents published by the FDA ahead of the meeting also suggested the agency is minded to approve Rexulti for this new use, which analysts have suggested could see a big step up in its prescribing. If approved, it would become the first approved treatment indicated for AAD in the US.

The FDA granted the new indication for the serotonin 5-HT1A and dopamine D2 partial agonist a priority review earlier this year, and is due to deliver its decision by 10th May.

The new application included data from two phase 3 trials – codenamed 331-12-283 and 331-14-213 – which found that Rexulti was more effective than placebo at improving scores on the Cohen-Mansfield Agitation Inventory (CMAI) scale over 12 weeks of follow up.

The CMAI is a caregivers’ rating scale focusing 29 agitation symptoms, each rated on a seven-point scale of frequency, and covers physically aggressive, physically non-aggressive, and verbally agitated behaviours. Behavioural and psychological symptoms are estimated to affect up to 90% of people living with dementia.

Analysts have suggested that approval for AAD could swell sales of Rexulti by $500 million to $1 billion, a big step up for a drug which currently makes around $1.4 billion in annual sales.

Other companies developing therapies of AAD include BioXcel Therapeutics, which already has an FDA green light for its Igalmi (dexmedetomidine) drug in agitation associated with schizophrenia and bipolar disorder, and has a phase 3 programme running in Alzheimer’s patients.

Axsome, meanwhile, recently reported positive results in its first phase 3 trial of AXS-05 (dextromethorphan-bupropion) in AAD, with a second study due to complete in the first half of next year. The combination was approved for MDD as Auvelity last year.

Photo by Jeremy Wong on Unsplash