FDA approves Rexulti for agitation tied to Alzheimer’s dementia

Daily therapy is first to be approved for this use in US

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has approved Rexulti (brexpiprazole) to treat agitation associated with dementia due to Alzheimer’s disease.

With this approval, Rexulti has now become the first and only therapy ever approved for this specific indication in the U.S.

“Today marks a major milestone for patients, caregivers, and families navigating the complexities of agitation associated with dementia due to Alzheimer’s disease,” Makoto Inoue, president and representative director of Otsuka Pharmaceutical, said in a press release. Otsuka co-developed Rexulti alongside Lundbeck.

Rexulti’s recommended starting dose for the treatment of agitation associated with dementia due to Alzheimer’s is 0.5 mg taken once daily for seven days, followed by 1 mg once daily for the next seven days, and by 2 mg once daily starting on day 15. The therapy’s dosing may be further increased to a maximum daily dose of 3 mg after at least 14 days, based on a patient’s clinical response and tolerability.

“This approval is a testament to our commitment and unwavering support of patients and caregivers to lessen the symptoms of agitation associated with dementia due to Alzheimer’s disease,” said Deborah Dunsire, Lundbeck’s president and CEO, adding, “We look forward to offering this first FDA-approved treatment option to address this significant unmet need for patients.”

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Rexulti is an antipsychotic medication that’s thought to work by modulating the activity of certain signaling molecules in the brain. The once-daily therapy previously had been approved to treat schizophrenia in patients ages 13 and older, as well as to treat major depressive disorder (MDD) in adults when given along antidepressant medications.

Importantly, Rexulti’s new approval covers its use as a once-daily treatment to help ease emotional symptoms over time. The therapy should not be used as an on-demand treatment on an “as needed” basis to control agitation associated with Alzheimer’s dementia.

Otsuka and Lundbeck’s supplemental new drug application seeking the approval of Rexulti for agitation associated with Alzheimer’s dementia was granted priority review by the FDA — a designation given to shorten the typical review time of therapies that have the potential to substantially improve care for serious conditions. Under priority review, the FDA issues its decision in six months rather than the typical 10 months.

Among Alzheimer’s patients, agitation — abnormal or inappropriate displays of emotion — is a common complaint, affecting as many as half of people with Alzheimer’s dementia.

“Agitation is one of the most common and challenging aspects of care among patients with dementia due to Alzheimer’s disease,” Tiffany Farchione, MD, director of the division of psychiatry in the FDA’s Center for Drug Evaluation and Research, said in a separate press release.

“‘Agitation’ can include symptoms ranging from pacing or restlessness to verbal and physical aggression,” Farchione said, noting that “these symptoms are leading causes of assisted living or nursing home placement and have been associated with accelerated disease progression

Rexulti’s new approval was supported by data from two Phase 3 trials — Study 331-12-283 (NCT01862640) and Study 331-14-213 (NCT03548584) — that together enrolled more than 700 people with agitation associated with Alzheimer’s dementia. In both trials, participants were given Rexulti or a placebo once daily for 12 weeks, or about three months.

The goal of these trials was to assess the impact of treatment on the frequency of agitation symptoms, as measured with a standard assessment tool called the Cohen-Mansfield Agitation Inventory.

Results showed that agitation scores decreased significantly more for patients given Rexulti — by 31% — than for those on the placebo.

“We are grateful to the patients and caregivers who participated in these important trials,” Dunsire said.

Agitation is one of the most common and challenging aspects of care among patients with dementia due to Alzheimer’s disease.

Safety data from these Alzheimer’s studies were generally consistent with the known safety profile of Rexulti in other populations. The most common side effects observed in patients with agitation associated with dementia due to Alzheimer’s included headache, dizziness, urinary tract infection, the common cold, and sleep disturbances.

The therapy also can cause serious side effects, including uncontrolled body movements (tardive dyskinesia), stroke and other problems with blood flow in the brain, high blood sugar (hyperglicemia) and diabetes. It also may cause neuroleptic malignant syndrome (NMS) — a potentially life-threatening condition characterized by symptoms like high fever, changes in heart rate and blood pressure, increased sweating, muscle stiffness, and confusion.

The therapy carries boxed warnings noting that Rexulti may increase the risk of death in elderly people with dementia-related psychosis (sensing or believing in things that are not real), as well as increase the risk of suicidal thoughts and actions in certain patients.