CoChat
Sign Up
Cited by 49Alzheimer's disease research and treatmentsBiomedical Ethics and RegulationPharmaceutical industry and healthcare

The Problem of Aducanumab for the Treatment of Alzheimer Disease

Alexander, G. Caleb, Karlawish, Jason·2021·Annals of Internal Medicine
DOI 10.7326/m21-2603
Open this paper in CoChat — free account

Abstract

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 by

Integrity signals

Registry

Crossref · 10.7326/m21-2603

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The FDA granted accelerated approval to aducanumab and stated that reduction of amyloid is reasonably likely to predict clinical benefit.

    “The FDA has controversially granted accelerated approval to aducanumab and has opined that the reduction of amyloid is reasonably likely to predict clinical benefit 7,9,[98][99][100][101][102][103][104][105][106][107] .”

    From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [98]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Alexander, G. C., & Karlawish, J.
Affiliations
  • Johns Hopkins University (US)
  • University of Pennsylvania (US)
ORCID
Venue
Annals of Internal Medicine
Publisher
American College of Physicians
Published
2021-09
Volume
174
Issue
9
Pages
1303-1304
ISSN
  • 0003-4819 (ISSN-L)
  • 1539-3704
DOI
10.7326/m21-2603
OpenAlex
W3167267423
Cited by
47
References
6
Citations by year
2025: 3 · 2024: 7 · 2023: 10 · 2022: 18 · 2021: 9
FWCI
7.22
Type
journal article
Language
en
Open access
closed
Licence
www.acpjournals.org/journal/aim/text-and-data-mining (tdm)
Locations
  • Annals of Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Physiology › Biomedical Ethics and Regulation
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmaceutical industry and healthcare
Keywords
aducanumab, Alzheimer's disease, FDA drug approval, accelerated approval, amyloid-beta, anti-amyloid therapy, confirmatory trials, regulatory review, drug efficacy, clinical trial design, Biogen, drug pricing, health care costs, clinical benefit assessment, informed consent, informed consent to treatment
MeSH terms
Alzheimer Disease, Humans, United States, United States Food and Drug Administration, Drug Approval, Antibodies, Monoclonal, Humanized

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review