FDA clears Rexulti as first drug for Alzheimer’s agitation

Lundbeck and Otsuka’s Rexulti has become the first drug to be approved by the FDA to treat agitation associated with Alzheimer’s disease, a common symptom of the neurodegenerative disorder.

The antipsychotic drug is already approved for schizophrenia and as an add-on therapy for people with major depressive disorder, but the new use will significantly expand the eligible patient population and could lead to an acceleration in sales.

Agitation in Alzheimer’s patients is one of the most difficult symptoms to manage, affecting around half of all patients with the disease, and places a big burden on patients, their families and carers. It can manifest as pacing, gesturing, profanity, shouting, shoving, and hitting, and is often the catalyst for patients having to leave their own homes and be placed in residential care.

Rexulti (brexpiprazole) is already one of the two drugmakers’ fastest-growing products, and analysts have suggested that the new use could swell sales by $500 million to $1 billion, which would be a big step up for a drug which currently makes around $1.4 billion in annual sales.

The question facing Lundbeck and Otsuka is whether they can persuade doctors to prescribe Rexulti over generic antipsychotics, anxiety medicines and antidepressants, which are already being used off-label to treat Alzheimer’s associated dementia.

The FDA has acknowledged these don’t have robust clinical data to support their use. Most comes from a host of smaller studies with varied designs and study populations, that have shown only small improvements in efficacy with concerns about their safety and tolerability - and some evidence pointing to an increase in mortality.

In the case of Rexulti, support for the new indication comes from a pair of phase 3 randomised clinical trials which collectively showed that the drug reduced agitation symptoms by around a third (31%) compared to placebo. It has been approved after a priority review at the FDA, used for drugs that promise to offer a significant improvement on current therapies.

In a statement, Lundbeck noted that Rexulti has been approved for daily dosing to Alzheimer’s patients with ongoing agitation, and is not indicated for intermittent use on an unscheduled, as-needed basis.

The drug may be the first to make it to approval for Alzheimer’s-related agitation in the US, but may soon be joined by other options.

BioXcel Therapeutics already has an FDA green light for Igalmi (dexmedetomidine) in agitation associated with schizophrenia and bipolar disorder, and has a phase 3 programme running in Alzheimer’s.

Axsome, meanwhile, has reported positive results in its first phase 3 trial of AXS-05 (dextromethorphan-bupropion) in Alzheimer’s agitation, with a second study due to complete in the first half of next year. The combination was approved for major depressive disorder as Auvelity last year.