The Problem of Aducanumab for the Treatment of Alzheimer Disease
Authors: G. Caleb Alexander, Jason Karlawish
Journal: Annals of Internal Medicine (2021)

Ideas and OpinionsSeptember 2021The Problem of Aducanumab for the Treatment of Alzheimer DiseaseG. Caleb Alexander, MD, MS and Jason Karlawish, MDG. Caleb Alexander, MD, MSJohns Hopkins Bloomberg School of Public Health and Johns Hopkins School of Medicine, Baltimore, Maryland (G.C.A.) and Jason Karlawish, MDUniversity of Pennsylvania, Philadelphia, Pennsylvania (J.K.).Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-2603 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail On 7 June 2021, the U.S. Food and Drug Administration (FDA) approved aducanumab for the treatment of Alzheimer disease. Biogen, the owner of the drug, will sell it as Aduhelm. The FDA's decision to approve aducanumab is among its most controversial ever. In this article, we examine the decision's implications for clinical research and patient care.Reverberating Problems With Drug Approval and ResearchAducanumab was approved despite the concerns of scientists and regulatory experts about its efficacy. Notably, an FDA statistician and an advisory committee on which one of us served (G.C.A.) reviewed the product at a November 2020 hearing ...References1. Alexander GC, Emerson S, Kesselheim AS. Evaluation of aducanumab for Alzheimer disease: scientific evidence and regulatory review involving efficacy, safety, and futility. JAMA. 2021;325:1717-8. [PMID: 33783469] doi:10.1001/jama.2021.3854 CrossrefMedlineGoogle Scholar2. Feuerstein A, Herper M. Biogen, FDA at odds over timing of crucial confirmatory trial of Alzheimer's drug. STAT News. 8 June 2021. Accessed at www.statnews.com/2021/06/08/biogen-fda-at-odds-over-timing-of-crucial-confirmatory-trial-of-alzheimers-drug on 14 June 2021. Google Scholar3. Gyawali B, Hey SP, Kesselheim AS. Assessment of the clinical benefit of cancer drugs receiving accelerated approval. JAMA Intern Med. 2019;179:906-13. [PMID: 31135808] doi:10.1001/jamainternmed.2019.0462 CrossrefMedlineGoogle Scholar4. Sevigny J, Chiao P, Bussière T, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature. 2016;537:50-6. [PMID: 27582220] doi:10.1038/nature19323 CrossrefMedlineGoogle Scholar5. Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled. Ann Intern Med. 1996;125:605-13. [PMID: 8815760] LinkGoogle Scholar6. Krudys KM. Aducanumab for the treatment of Alzheimer's disease: clinical overview of efficacy. Presented at the meeting of the Peripheral and Central Nervous System Drugs Advisory Committee, 6 November 2020. Accessed at www.fda.gov/media/143504/download on 7 January 2021. Google Scholar7. Panza F, Lozupone M, Logroscino G, et al. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat Rev Neurol. 2019;15:73-88. [PMID: 30610216] doi:10.1038/s41582-018-0116-6 CrossrefMedlineGoogle Scholar8. Grill JD, Karlawish J. Implications of FDA approval of a first disease-modifying therapy for a neurodegenerative disease on the design of subsequent clinical trials. Neurology. 2021. [PMID: 34088880] doi:10.1212/WNL.0000000000012329 CrossrefMedlineGoogle Scholar9. Lin GA, Whittington MD, Synnott PG, et al. Aducanumab for Alzheimer's Disease: Effectiveness and Value. Draft Evidence Report. Institute for Clinical and Economic Review. 5 May 2021. Accessed at https://icer.org/wp-content/uploads/2020/10/ICER_ALZ_Draft_Evidence_Report_050521.pdf on 14 June 2021. Google Scholar10. Biogen; Eisai. ADUHELM (aducanumab-avwa) injection, for intravenous use. Prescribing information. Accessed at www.accessdata.fda.gov/drugsatfda_docs/label/2021/761178s000lbl.pdf on 14 June 2021. Google Scholar Author, Article, and Disclosure InformationAffiliations: Johns Hopkins Bloomberg School of Public Health and Johns Hopkins School of Medicine, Baltimore, Maryland (G.C.A.)University of Pennsylvania, Philadelphia, Pennsylvania (J.K.).Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-2603.Corresponding Author: G. Caleb Alexander, MD, MS, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, W6035, Baltimore, MD 21205; e-mail, [email protected]edu.Current Author Addresses: Dr. Alexander: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, W6035, Baltimore, MD 21205.Dr. Karlawish: University of Pennsylvania, 3615 Chestnut Street, Philadelphia, PA 19130.Author Contributions: Conception and design: G.C. Alexander, J. Karlawish.Analysis and interpretation of the data: J. Karlawish.Drafting of the article: G.C. Alexander, J. Karlawish.Critical revision of the article for important intellectual content: G.C. Alexander, J. Karlawish.Final approval of the article: G.C. Alexander, J. Karlawish.This article was published at Annals.org on 17 June 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byU.S. Food and Drug Administration Reasoning in Approval Decisions When Efficacy Evidence Is Borderline, 2013–2018Perrine Janiaud, PhD, Telba Irony, PhD, Estelle Russek-Cohen, PhD, and Steven N. Goodman, MD, PhDChemical update on the potential for serotonin 5-HT6 and 5-HT7 receptor agents in the treatment of Alzheimer's diseaseAducanumab Fails to Produce Efficacy Results Yet Obtains US Food and Drug Administration ApprovalAducanumab and the Medicalization (Still) of Alzheimer's Disease: A Challenge to Measure and Act On What Matters September 2021Volume 174, Issue 9Page: 1303-1304KeywordsAlzheimer diseaseDrug policyDrugsMild cognitive impairment ePublished: 17 June 2021 Issue Published: September 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...