FDA Approves First Drug to Treat Dementia-Associated Agitation in AD Patients
Individuals who received two mg or three mg of Rexulti showed statistically significant and clinically meaningful improvements
The U.S. Food and Drug Administration recently announced the supplemental approval of Rexulti (brexpiprazole) oral tablets for the treatment of agitation associated with dementia due to Alzheimer’s disease (AD). 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,” said Tiffany Farchione, MD, director of the Division of Psychiatry in 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 serious and debilitating neurological condition characterized by a progressive decline in one or more cognitive domains in the brain. Dementia can seriously impair an individual’s ability to function independently. Many people living with dementia require permanent at-home or residential care. AD is an irreversible, progressive brain disorder—and the most common cause of dementia—affecting more than 6.5 million Americans. Patients with dementia often have behavioral and psychological disturbances. Agitation is among the most persistent, complex, stressful, and costly aspects of care among patients with behavioral and psychological symptoms of dementia.
Efficacy of Rexulti for treating AD-associated agitation
The effectiveness of Rexulti for the treatment of agitation associated with dementia due to Alzheimer’s disease was determined through two 12-week, randomized, double-blind, placebo-controlled, fixed-dose studies. In these studies, patients were required to have a probable diagnosis of Alzheimer’s dementia; have a score between 5 and 22 on the Mini-Mental State Examination, a test that detects whether a person is experiencing cognitive impairment; and exhibit the type, frequency, and severity of agitation behaviors that require medication. Trial participants ranged between 51 and 90 years of age.
In the first study, patients received one or two milligrams (mg) of Rexulti; in the second study, patients received two or three 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. CMAI is a survey tool that uses input from caregivers to rate the frequency of certain agitative behaviors in dementia patients on a scale of one to seven. In both studies, patients who received two mg or three mg of Rexulti showed statistically significant and clinically meaningful improvements in total CMAI scores compared to patients in the placebo group at week 12.
Dose recommendations and side effects of Rexulti
The recommended starting dosage for the treatment of agitation associated with dementia due to AD is 0.5 mg taken once daily on days one to seven. Patients should increase the dosage on days eight through 14 to one mg, once daily, and on day 15 to two mg, once daily. The recommended target dose is two mg once daily. Based on clinical response and tolerability, the dosage can be increased to the maximum recommended daily dosage of three mg once daily after at least 14 days.
The most common side effects among patients with agitation associated with dementia due to AD include headache, dizziness, urinary tract infection, nasopharyngitis, and sleep disturbances (both somnolence and insomnia). Rexulti will retain the Boxed Warning for medications in this class that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
The FDA granted this application Fast Track designation (Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need). The purpose is to get important new drugs to the patient earlier. The supplemental approval of Rexulti was granted to Otsuka Pharmaceutical Company Ltd., and Lundbeck Inc.
- This press release was originally published on the U.S. Food and Drug Administration website