Skip to main content
SpringerLink
Log in

Aducanumab: a review of the first approved amyloid-targeting antibody for Alzheimer’s disease

  • Review Article
  • Published:
Drugs & Therapy Perspectives Aims and scope Submit manuscript

Abstract

Aducanumab is a human immunoglobulin G1 monoclonal antibody that binds to the linear epitope formed by amino acids 3–7 of the Aβ peptide, with a higher affinity for fibrillar aggregates as compared with monomers. It has become the first amyloid-targeting antibody to be approved for Alzheimer’s disease patients with mild cognitive impairment or the mild dementia stage of the disease. However, the controversial accelerated approval of this drug in June 2021 by the Food and Drug Administration (FDA) has set up a debate amongst the Alzheimer’s scientific community. While this drug promises to be the only approved disease-modifying agent in the Alzheimer’s disease arena, it comes with its own share of uncertainties surrounding the results of the clinical trials, a high cost burden, and significant adverse effects in the form of amyloid-related imaging abnormalities (ARIA). This article provides a detailed insight into the pharmacological profile and clinical trials information of aducanumab, discussing the limitations surrounding its approval, and its current status in Alzheimer’s disease.

Plain Language Summary

Alzheimer’s disease (AD) is the leading cause of dementia worldwide. This disease is associated with the deposition of amyloid peptides in the brain. These peptides aggregate to form plaques which lead to neurodegeneration and cognitive decline. The currently approved drugs that are used in the treatment of AD disease provide only symptomatic relief to the patients without affecting the underlying pathology. Aducanumab is an amyloid-targeting monoclonal antibody that binds to the Aβ peptides and causes a decrease in amyloid accumulation. This is first such drug to be approved by the US Food and Drug Administration (FDA) for AD. It is indicated in AD patients with mild cognitive impairment or at the mild dementia stage of the disease as monthly intravenous infusions. While one of its phase III clinical trials demonstrated a reduction in the cognitive decline, the other phase III trial has failed to do so. Hence, its efficacy is still uncertain and the results of a further trial are needed to shed more light on this. Besides, a significant risk of amyloid-related imaging abnormalities (ARIA) is noted with the use of this drug. Hence, its administration requires MRI monitoring. The high cost of this drug is also a hindrance to its widespread use, especially in low- and middle-income countries. Despite this, it is the only approved drug for AD that can modify the course of this disease. In future, more such therapies with improved efficacy and safety could improve treatment options and highly benefit patients with this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. World Health Organization. Dementia (Fact Sheet). 2 Sep 2021. https://www.who.int/news-room/fact-sheets/detail/dementia. Accessed 12 Mar 2022.

  2. Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol. 2018;25(1):59–70.

    Article  CAS  Google Scholar 

  3. Briggs R, Kennelly SP, O’Neill D. Drug treatments in Alzheimer’s disease. Clin Med (Lond). 2016;16(3):247–53.

    Article  Google Scholar 

  4. Arndt JW, Qian F, Smith BA, et al. Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β. Sci Rep. 2018;8(1):1–16.

    Article  Google Scholar 

  5. Liu J, Yang B, Ke J, et al. Antibody-based drugs and approaches against amyloid-β species for Alzheimer’s disease immunotherapy. Drugs Aging. 2016;33(10):685–97.

    Article  CAS  Google Scholar 

  6. Abyadeh M, Gupta V, Gupta V, et al. Comparative analysis of aducanumab, zagotenemab and pioglitazone as targeted treatment strategies for Alzheimer’s disease. Aging Dis. 2021;12(8):1964–76.

    Article  Google Scholar 

  7. U.S. Food and Drug Administration. FDA Grants Accelerated Approval for Alzheimer’s Drug [media release]. 7 Jun 2021. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug. Accessed 12 Mar 2022.

  8. Biogen Inc. FDA Approves Updated ADUHELMTM Prescribing Information to Emphasize Population Studied in Clinical Trials [media release].8 Jul 2021. https://investors.biogen.com/news-releases/news-release-details/fda-approves-updated-aduhelmtm-prescribing-information-emphasize. Accessed 13 Mar 2022.

  9. National Library of Medicine. ChemIDplus - 1384260-65-4 - Aducanumab [USAN:INN]. https://chem.nlm.nih.gov/chemidplus/rn/1384260-65-4. Accessed 14 Mar 2022.

  10. World Health Organization Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index. https://www.whocc.no/atc_ddd_index/?code=N06DX03. Accessed 14 Mar 2022.

  11. Biogen. ADUHELM® (aducanumab-avwa) injection, for intravenous use [US prescribing information]. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761178s000lbl.pdf. Accessed 13 Mar 2022.

  12. Cummings J, Aisen P, Apostolova LG, et al. Aducanumab: appropriate use recommendations. J Prev Alzheimers Dis. 2021;8(4):398–410.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Padda IS, Parmar M. Aducanumab. [Updated 2022 Jan 6]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022. https://www.ncbi.nlm.nih.gov/books/NBK573062/. Accessed 13 Mar 2022.

  14. Salloway S, Chalkias S, Barkhof F, et al. Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurol. 2022;79(1):13–21.

    Article  Google Scholar 

  15. Bussiere T, Weinreb PH, Dunstan RW, et al. Differential in vitro and in vivo binding profiles of BIIB037 and other anti-abeta clinical antibody candidates. Neurodegener Dis. 2013;11(Suppl 1):2576. http://misc.karger.com/websites/NDD_2013_011_s_1/AbstractCD/pdf/787.pdf. Accessed 8 Mar 2022.

  16. Kastanenka KV, Bussiere T, Shakerdge N, et al. Immunotherapy with aducanumab restores calcium homeostasis in Tg2576 mice. J Neurosci. 2016;36(50):12549–58.

    Article  CAS  Google Scholar 

  17. Bastrup J, Hansen KH, Poulsen TBG, et al. Anti-Aβ antibody aducanumab regulates the proteome of senile plaques and closely surrounding tissue in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis. 2021;79(1):249–65.

    Article  CAS  Google Scholar 

  18. Kuchibhotla KV, Goldman ST, Lattarulo CR, et al. Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron. 2008;59(2):214–25.

    Article  CAS  Google Scholar 

  19. Ishii M, Hiller AJ, Pham L, et al. Amyloid-beta modulates low-threshold activated voltage-gated L-type calcium channels of arcuate neuropeptide y neurons leading to calcium dysregulation and hypothalamic dysfunction. J Neurosci. 2019;39(44):8816–25.

    Article  Google Scholar 

  20. Cummings J, Aisen P, Lemere C, et al. Aducanumab produced a clinically meaningful benefit in association with amyloid lowering. Alzheimers Res Ther. 2021;13(1):98.

    Article  Google Scholar 

  21. Ferrero J, Williams L, Stella H, et al. First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer’s disease. Alzheimers Dement (N Y). 2016;2(3):169–76.

    Article  Google Scholar 

  22. Sevigny J, Chiao P, Bussière T, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016;537(7618):50–6.

    Article  CAS  Google Scholar 

  23. US National Institutes of Health. ClinicalTrials.gov identifier NCT01397539, Single Ascending Dose Study of BIIB037 in Participants With Alzheimer’s Disease. 2015. https://clinicaltrials.gov/ct2/show/NCT01397539. Accessed 10 Mar 2022.

  24. US National Institutes of Health. ClinicalTrials.gov identifier NCT01677572, Multiple Dose Study of Aducanumab (BIIB037) (Recombinant, Fully Human Anti-Aβ IgG1 mAb) in Participants With Prodromal or Mild Alzheimer’s Disease. 2020. https://clinicaltrials.gov/ct2/show/NCT01677572. Accessed 10 Mar 2022.

  25. US National Institutes of Health. ClinicalTrials.gov identifier NCT02434718, Single and Multiple Ascending Dose Study of Aducanumab (BIIB037) in Japanese Participants With Alzheimer’s Disease. 2020. https://clinicaltrials.gov/ct2/show/NCT02434718. Accessed 10 Mar 2022.

  26. US National Institutes of Health. ClinicalTrials.gov identifier NCT02782975, Absolute Bioavailability of a Single, Fixed Subcutaneous Dose of Aducanumab in Healthy Participants. 2017. https://clinicaltrials.gov/ct2/show/NCT02782975. Accessed 10 Mar 2022.

  27. US National Institutes of Health. ClinicalTrials.gov identifier NCT04924140, A Study to Assess Absolute Bioavailability of Aducanumab in Healthy Volunteer. 2021. https://clinicaltrials.gov/ct2/show/NCT04924140. Accessed 10 Mar 2022.

  28. US National Institutes of Health. ClinicalTrials.gov identifier NCT05216887, A Study to Assess the Pharmacokinetic (PK) Comparability of 2 Fixed Subcutaneous (SC) Doses of Aducanumab (BIIB037) With a Single, Weight-Based Intravenous (IV) Dose in Healthy Volunteers. 2022. https://clinicaltrials.gov/ct2/show/NCT05216887. Accessed 10 Mar 2022.

  29. US National Institutes of Health. ClinicalTrials.gov identifier NCT03639987, A Study of Aducanumab in Participants With Mild Cognitive Impairment Due to Alzheimer’s Disease or With Mild Alzheimer’s Disease Dementia to Evaluate the Safety of Continued Dosing in Participants With Asymptomatic Amyloid-Related Imaging Abnormalities. 2021. https://clinicaltrials.gov/ct2/show/results/NCT03639987. Accessed 10 Mar 2022.

  30. US National Institutes of Health. ClinicalTrials.gov identifier NCT02477800, 221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer’s Disease. 2021. https://clinicaltrials.gov/ct2/show/NCT02477800. Accessed 10 Mar 2022.

  31. Biogen Inc. Biogen Plans Regulatory Filing for Aducanumab in Alzheimer’s Disease Based on New Analysis of Larger Dataset from Phase 3 Studies [media release]. 22 Oct 2019. https://investors.biogen.com/news-releases/news-release-details/biogen-plans-regulatory-filing-aducanumab-alzheimers-disease. Accessed 10 Mar 2022.

  32. US National Institutes of Health. ClinicalTrials.gov identifier NCT02484547, 221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer’s Disease. 2021. https://clinicaltrials.gov/ct2/show/NCT02484547. Accessed 10 Mar 2022.

  33. US National Institutes of Health. ClinicalTrials.gov identifier NCT04241068, A Study to Evaluate Safety and Tolerability of Aducanumab in Participants With Alzheimer’s Disease Who Had Previously Participated in the Aducanumab Studies 221AD103, 221AD301, 221AD302 and 221AD205. 2021. https://clinicaltrials.gov/ct2/show/NCT04241068. Accessed 10 Mar 2022.

  34. US National Institutes of Health. ClinicalTrials.gov identifier NCT05108922, A Study of Donanemab (LY3002813) Compared With Aducanumab in Participants With Early Symptomatic Alzheimer’s Disease (TRAILBLAZER-ALZ 4). 2022. https://clinicaltrials.gov/ct2/show/NCT05108922. Accessed 10 Mar 2022.

  35. US National Institutes of Health. ClinicalTrials.gov identifier NCT05097131, An Observational Study of Aducanumab-avwa in Participants With Alzheimer’s Disease in the US. 2022. https://clinicaltrials.gov/ct2/show/NCT05097131. Accessed 10 Mar 2022.

  36. Biogen Inc. Biogen and Eisai Announce Design of ADUHELM ICARE AD-US Study, the First Real-World Observational Phase 4 Study in Alzheimer’s Disease at AAIC 2021 [media release].29 Jul 2021. https://investors.biogen.com/news-releases/news-release-details/biogen-and-eisai-announce-design-aduhelm-icare-ad-us-study-first. Accessed 13 Mar 2022.

  37. US National Institutes of Health. ClinicalTrials.gov identifier NCT05310071, A Study to Verify the Clinical Benefit of Aducanumab in Participants With Early Alzheimer's Disease (ENVISION). 2022. https://clinicaltrials.gov/ct2/show/NCT05310071. Accessed 7 Aug 2022.

  38. Biogen Inc. Update on the Phase 4 ENVISION Confirmatory Study of ADUHELM® [media release].27 Jan 2022. https://investors.biogen.com/news-releases/news-release-details/update-phase-4-envision-confirmatory-study-aduhelmr. Accessed 13 Mar 2022.

  39. Budd Haeberlein S, Aisen PS, Barkhof F, et al. Two randomized phase 3 studies of aducanumab in early Alzheimer’s disease. J Prev Alzheimer’s Dis. 2022;9(2):197–210.

    CAS  Google Scholar 

  40. Lozupone M, Solfrizzi V, D’Urso F, et al. Anti-amyloid-β protein agents for the treatment of Alzheimer’s disease: an update on emerging drugs. Expert Opin Emerg Drugs. 2020;25(3):319–35.

    Article  CAS  Google Scholar 

  41. U.S. Food and Drug Administration (FDA). Aducanumab for the treatment of Alzheimer’s disease: clinical overview of efficacy. Peripheral and Central Nervous System (PCNS) Drugs Advisory Committee Meeting [Online]. 2020. https://www.fda.gov/media/143504/download. Accessed 6 Aug 2022.

  42. Sperling RA, Jack CR, Black SE, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimer’s Dement. 2011;7(4):367–85.

    Article  Google Scholar 

  43. Cummings JL, Tong G, Ballard C. Treatment Combinations for Alzheimer’s disease: current and future pharmacotherapy options. J Alzheimers Dis. 2019;67(3):779–94.

    Article  Google Scholar 

  44. European Medicines Agency. Aduhelm: Withdrawal of the marketing authorisation application.2022. https://www.ema.europa.eu/en/medicines/human/withdrawn-applications/aduhelm. Accessed 13 May 2022.

  45. Biogen Inc. Biogen Files New Drug Application for Aducanumab in Japan [media release].9 Dec 2020. https://investors.biogen.com/news-releases/news-release-details/biogen-files-new-drug-application-aducanumab-japan. Accessed 13 Mar 2022.

  46. Chertkow H, Rockwood K, Hogan DB, et al. Consensus statement regarding the application of biogen to health Canada for approval of aducanumab. Can Geriatr J. 2021;24(4):373–8.

    Article  Google Scholar 

  47. Biogen Inc. Japan’s First Committee on New Drugs of The Pharmaceutical Affairs and Food Sanitation Council Seeks Additional Data; Aducanumab Remains under Review [media release].22 Dec 2021. https://investors.biogen.com/news-releases/news-release-details/japans-first-committee-new-drugs-pharmaceutical-affairs-and-food. Accessed 13 Mar 2022.

  48. Whittington MD, Campbell JD, Rind D, et al. Cost-effectiveness and value-based pricing of aducanumab for patients with early Alzheimer disease. Neurology. 2022;98(9):e968–77.

    Article  CAS  Google Scholar 

  49. Synnott PG, Whittington MD, Lin GA, et al. The effectiveness and value of aducanumab for Alzheimer’s disease. J Manag Care Spec Pharm. 2021;27(1):1613–7.

    PubMed  Google Scholar 

  50. Tolar M, Abushakra S, Hey JA, et al. Aducanumab, gantenerumab, BAN2401, and ALZ-801—The first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval. Alzheimer’s Res Ther. 2020;12(1):1–10.

    Google Scholar 

  51. Being Patient. FDA Speeds Up Process for Two More Experimental Alzheimer’s Drugs: Donanemab, Lecanemab. 24 Jun 2021. https://www.beingpatient.com/eli-lilly-biogen-eisai-donanemab-lecanemab-fda-breakthrough-status/. Accessed 7 Aug 2022.

Download references

Acknowledgments

None.

Author information

Authors and Affiliations

  1. Department of Pharmacology, University College of Medical Sciences and GTB hospital, New Delhi, India

    Shubhima Grover

  2. Department of Pharmacology, University College of Medical Sciences and GTB hospital, New Delhi, India

    Seema Jain

Authors
  1. Shubhima Grover
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seema Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seema Jain.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Authorship

Both the authors have contributed equally to the conception and planning of work, literature search, drafting of the manuscript and are responsible for the content of the article.

Conflict of interest

The authors declare no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent to publish

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grover, S., Jain, S. Aducanumab: a review of the first approved amyloid-targeting antibody for Alzheimer’s disease. Drugs Ther Perspect 38, 443–454 (2022). https://doi.org/10.1007/s40267-022-00944-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40267-022-00944-4

Search

Navigation