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(A version of this column appeared in the June 2023 issue of Public Citizen’s Health Letter.)
On May 10, 2023, the Food and Drug Administration (FDA) approved a supplemental indication for the antipsychotic medication brexpiprazle (REXULTI) for agitation symptoms associated with dementia due to Alzheimer’s disease.[1] At an advisory committee meeting in April 2023[2] and in a subsequent letter to the FDA,[3] Public Citizen’s Health Research Group had urged the agency to reject the...
(A version of this column appeared in the June 2023 issue of Public Citizen’s Health Letter.)
On May 10, 2023, the Food and Drug Administration (FDA) approved a supplemental indication for the antipsychotic medication brexpiprazle (REXULTI) for agitation symptoms associated with dementia due to Alzheimer’s disease.[1] At an advisory committee meeting in April 2023[2] and in a subsequent letter to the FDA,[3] Public Citizen’s Health Research Group had urged the agency to reject the supplemental indication. In our view, the drug’s small benefits do not outweigh its substantial risks, and no population of patients has been identified for which the benefits outweigh the risks.
Agitation symptoms associated with dementia due to Alzheimer’s disease are a frequent and often disturbing clinical problem and a vexing issue for patients and families. Unfortunately, the supplemental indication for brexpiprazole may offer false hope because the evidence of clinically meaningful benefits is not at all compelling.
The FDA first approved brexpiprazole in 2015 for adults with major depressive disorder or schizophrenia.[4] Subsequently, it granted Otsuka Pharmaceutical Company Ltd. and Lundbeck Inc. a fast-track review for the supplemental indication. All antipsychotics, including brexpiprazole, have a black-box warning because they are associated with an increased risk of death among elderly patients with dementia.
The serious risks focus attention on the limited benefits of brexpiprazole for agitation symptoms associated with dementia due to Alzheimer’s disease. For example, the treatment difference in favor of brexpiprazole in one of the studies used to support the supplemental approval was just 3.8 points on an “agitation inventory” score that ranges from 29 to 203 points.[5] Improvements were seen in subjects receiving brexpiprazole (21.6 points), but also in subjects receiving placebo (17.8 points).[6] The 2.2% difference on this score between the groups is unlikely to be clinically important for patients.
Brexpiprazole is the first — and, for now, the only — FDA-approved treatment option for agitation among patients with agitation symptoms associated with dementia due to Alzheimer’s disease. The supplemental indication may lead to hundreds of millions of dollars in annual sales for brexpiprazole and applications from other companies to market similar drugs.[7] Patients and families, however, need drugs that offer clinically meaningful benefits that clearly outweigh their risks. The FDA would best serve patients by using higher standards to approve new drugs and supplemental indications for existing drugs.
References
[1] Food and Drug Administration. FDA approves first drug to treat agitation symptoms associated with dementia due to Alzheimer’s disease. May 11, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-agitation-symptoms-associated-dementia-due-alzheimers-disease?utm_medium=email&utm_source=govdelivery. Accessed June 6, 2023.
[2] Public Citizen. Testimony before the FDA’s joint meeting of the Psychopharmacologic Drugs Advisory Committee and the Peripheral and Central Nervous System Drugs Advisory Committee regarding brexpiprazole. April 14, 2023. https://www.citizen.org/article/testimony-before-the-fdas-joint-meeting-of-the-psychopharmacologic-drugs-advisory-committee-and-the-peripheral-and-central-nervous-system-drugs-advisory-committee-regarding-brexpiprazole/. Accessed June 6, 2023.
[3] Public Citizen. Letter to the FDA regarding brexpiprazole. May 3, 2023. https://www.citizen.org/wp-content/uploads/2656.pdf. Accessed June 6, 2023.
[4] Rexulti: Highlights of Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/205422s009lbl.pdf. Accessed June 6, 2023.
[5] Food and Drug Administration. FDA briefing document. NDA 205422/S-009, drug name brexpiprazole; joint meeting of the Psychopharamacologic Drugs Advisory Committee and the Peripheral and Central Nervous System Advisory Committee. April 14, 2023. https://www.fda.gov/media/167066/download. Accessed June 6, 2023.
[6] Ibid.
[7] DeArment A. Otsuka/Lundbeck’s Rexulti has time to build a lead in the Alzheimer’s agitation market. May 11, 2023. https://scrip.pharmaintelligence.informa.com/SC148364/OtsukaLundbecks-Rexulti-Has-Time-To-Build-A-Lead-In-The-Alzheimers-Agitation-Market. Accessed June 6, 2023.
