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November 30, 2020

Possible Consequences of the Approval of a Disease-Modifying Therapy for Alzheimer Disease

Author Affiliations
  • 1Knight Alzheimer’s Disease Research Center, Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri
JAMA Neurol. 2021;78(2):141-142. doi:10.1001/jamaneurol.2020.4478

On July 8, 2020, Biogen submitted an application to the US Food and Drug Administration (FDA) for approval of aducanumab for the treatment of Alzheimer disease (AD) dementia. Aducanumab, a monoclonal antibody targeting aggregated amyloid-β, showed in a phase 3 clinical trial (but apparently not in another phase 3 trial) success in clearing amyloid plaques from the brain and slowing the rate of cognitive decline in some patients with mild AD dementia.1 While the aducanumab clinical trial data are complicated and the path to approval far from clear, approval is certainly possible, and other promising antibodies (such as Biogen’s BAN-2401 and Genentech’s gantenerumab) are just steps behind. Thus, the long-awaited advent of disease-modifying therapy for AD may be soon upon us, representing a major advance in the battle against AD and a beacon of much-needed hope for patients. However, the potential seismic effect of a disease-modifying therapy for AD requires serious consideration because it could present significant challenges for AD clinical practice and research, some of which are considered here.

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    1 Comment for this article
    Aducanumab approval and quality of life
    Ronald Louie, MD | University of Washington
    The authors are right to point out the various impacts of FDA approval for a disease-modifying therapy, especially for dementia, where the pent-up demand and the outcome measures are complicated.

    Since the pertinent FDA advisory committee voting was reportedly negative for aducanumab as it examined the data, one can assume that even if approved, this agent may not have tremendous impact.

    Dr. Jason Karlawish had written a "thought experiment" last year as an "First Opinion" piece in STATnews that delves into practical logistics and financial implications of an approval.

    FDA does approve many cancer agents with marginal
    data and marginal impact; one recent article (cited below) in this journal found that aggregating 92 agents approved recently, median survival increased only two months. Quality of life was not reported; it is hard to determine the value of two months of prolonged survival. Likewise, in dementia care, quality of life should be a consideration if agents prolong survival.

    Ladanie A, Schmitt AM, Speich B, et al. Clinical Trial Evidence Supporting US Food and Drug Administration Approval of Novel Cancer Therapies Between 2000 and 2016. JAMA Netw Open. 2020;3(11):e2024406. doi:10.1001/jamanetworkopen.2020.24406