FDA approves first drug to treat symptoms of agitation associated with dementia due to Alzheimer's disease
Friday, May 12, 2023
Today, the US Food and Drug Administration (FDA) granted supplemental approval for Rexulti oral tablets (brexpiprazole) for the treatment of agitation associated with dementia due to Alzheimer's disease. This is the first FDA-approved treatment option for this indication.
"Agitation is one of the most common and challenging aspects of care among patients with dementia due to Alzheimer's disease. 'Agitation' can include symptoms ranging from pacing or restlessness to verbal and physical aggression," he said Dr. Tiffany Farchione , director of the Division of Psychiatry at the FDA's Center for Drug Evaluation and Research. "These symptoms are leading causes of assisted living or nursing home placement and have been associated with accelerated disease progression."
Dementia is a severe and debilitating neurological condition characterized by progressive deterioration in one or more cognitive domains of the brain. Dementia can severely affect a person's ability to function independently. Many people living with dementia require permanent care in the home or nursing home. Alzheimer's disease is the most common cause of dementia. Alzheimer's disease is a progressive and irreversible brain disorder that affects more than 6.5 million people in the United States. Patients with dementia frequently have behavioral and psychological disorders. Agitation is among the most persistent, complex, stressful, and costly aspects of care among patients with behavioral and psychological symptoms of dementia.
The effectiveness of Rexulti for the treatment of agitation associated with dementia caused by Alzheimer's disease was determined in two 12-week, randomized, double-blind, placebo-controlled, fixed-dose studies. In these studies, patients had to have a probable diagnosis of Alzheimer's dementia; score between 5 and 22 on the Mini Mental State Exam, a test that detects whether a person is experiencing cognitive decline; and show the type, frequency, and severity of agitating behaviors that require medication. Trial participants were between 51 and 90 years of age.
In the first study, patients received 1 or 2 milligrams (mg) of Rexulti; in the second study, patients received 2 or 3 mg of Rexulti. The primary efficacy endpoint in these two studies was the change from baseline in the Cohen-Mansfield Agitation Inventory (CMAI) total score at week 12. The CMAI is a survey tool that uses input from caregivers to rate the frequency of some agitated behaviors in patients with dementia on a scale of 1 to 7. In both studies, patients receiving Rexulti 2 mg or 3 mg showed statistically significant and clinically significant improvements in CMAI total scores compared to patients in the placebo group at week 12.
The recommended starting dose for treatment of agitation associated with Alzheimer's dementia is 0.5 mg once daily on days 1 through 7. Patients should increase the dose on days 8 through 14 to 1 mg once daily. , and on day 15 to 2 mg once a day. The recommended target dose is 2 mg once daily. The dose may be increased to the maximum recommended daily dose of 3 mg once daily after at least 14 days, based on clinical response and tolerability.
The most frequent side effects among patients with agitation associated with dementia due to Alzheimer's disease include headache, dizziness, urinary tract infection, nasopharyngitis, and sleep disturbances (drowsiness and insomnia). Rexulti will retain the boxed warning for medicines in this class that elderly patients with dementia-related psychosis treated with antipsychotic medicines are at increased risk of death.
