Skip to main content

Advertisement

SpringerLink
Log in

Commentaries: Lecanemab: pioneering the way as the first approved drug for Alzheimer’s disease treatment

  • Comment
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and neuronal abnormalities. Current therapies address symptoms without altering disease progression. Lecanemab, an anti-amyloid antibody, binds to amyloid-beta (Aβ) protofibrils. Phase II trials revealed dose-dependent amyloid clearance and reduced clinical decline. Phase III trials demonstrated cognitive benefits with potential adverse events. Full FDA approval was granted for lecanemab due to its ability to eliminate toxic brain amyloids. However, longer trials are needed to assess its efficacy and safety. While lecanemab marks a significant advancement, further breakthroughs are essential for effective AD treatment.

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
Fig. 2

References

  1. Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056.

    Article  PubMed  Google Scholar 

  2. Ke PC, Zhou R, Serpell LC, Riek R, Knowles TPJ, Lashuel HA, et al. Half a century of amyloids: past, present and future. Chem Soc Rev. 2020;49:5473–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, et al. The ‘Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Abeta protofibril formation. Nat Neurosci. 2001;4:887–93.

    Article  CAS  PubMed  Google Scholar 

  4. O’Nuallain B, Freir DB, Nicoll AJ, Risse E, Ferguson N, Herron CE, et al. Amyloid beta-protein dimers rapidly form stable synaptotoxic protofibrils. J Neurosci. 2010;30:14411–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Avgerinos KI, Ferrucci L, Kapogiannis D. Effects of monoclonal antibodies against amyloid-beta on clinical and biomarker outcomes and adverse event risks: a systematic review and meta-analysis of phase III RCTs in Alzheimer’s disease. Ageing Res Rev. 2021;68: 101339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Volloch V, Rits-Volloch S. Effect of Lecanemab in early Alzheimer’s disease: mechanistic interpretation in the amyloid cascade hypothesis 2.0 perspective. J Alzheimers Dis. 2023;93:1277–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zemek F, Drtinova L, Nepovimova E, Sepsova V, Korabecny J, Klimes J, et al. Outcomes of Alzheimer’s disease therapy with acetylcholinesterase inhibitors and memantine. Expert Opin Drug Saf. 2014;13:759–74.

    CAS  PubMed  Google Scholar 

  8. Mufson EJ, Counts SE, Perez SE, Ginsberg SD. Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications. Expert Rev Neurother. 2008;8:1703–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hoy SM. Lecanemab: first approval. Drugs. 2023;83:359–65.

    Article  CAS  PubMed  Google Scholar 

  10. Daly T, Epelbaum S. The accelerated approval of Aducanumab invites a rethink of the current model of drug development for Alzheimer’s disease. AJOB Neurosci. 2022. https://doi.org/10.1080/21507740.2022.2048721.

    Article  PubMed  Google Scholar 

  11. van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388:9–21.

    Article  PubMed  Google Scholar 

  12. Reiman EM. Drug trial for Alzheimer’s disease is a game changer. Nature. 2023;615:42–3.

    Article  CAS  PubMed  Google Scholar 

  13. FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval. FDA NEWS RELEASE, 2023.

  14. Chin E, Jaqua E, Safaeipour M, Ladue T. Conventional versus new treatment: comparing the effects of acetylcholinesterase inhibitors and N-Methyl-D-aspartate receptor antagonist with aducanumab. Cureus. 2022;14: e31065.

    PubMed  PubMed Central  Google Scholar 

  15. Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M, et al. The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature. 2016;537:50–6.

    Article  CAS  PubMed  Google Scholar 

  16. Knopman DS, Jones DT, Greicius MD. Failure to demonstrate efficacy of aducanumab: an analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019. Alzheimers Dement. 2021;17:696–701.

    Article  PubMed  Google Scholar 

  17. Budd Haeberlein S, Aisen PS, Barkhof F, Chalkias S, Chen T, Cohen S, et al. Two randomized phase 3 studies of Aducanumab in early Alzheimer’s disease. J Prev Alzheimers Dis. 2022;9:197–210.

    CAS  PubMed  Google Scholar 

  18. Jeong SY, Suh CH, Shim WH, Lim JS, Lee JH, Kim SJ. Incidence of amyloid-related imaging abnormalities in patients With Alzheimer disease treated with anti-beta-amyloid immunotherapy: a meta-analysis. Neurology. 2022;99:e2092–101.

    Article  CAS  PubMed  Google Scholar 

  19. Villain N, Planche V, Levy R. High-clearance anti-amyloid immunotherapies in Alzheimer’s disease Part 1: meta-analysis and review of efficacy and safety data, and medico-economical aspects. Rev Neurol. 2022;178:1011–30.

    Article  CAS  PubMed  Google Scholar 

  20. Synnott PG, Whittington MD, Lin GA, Rind DM, Pearson SD. The effectiveness and value of aducanumab for Alzheimer’s disease. J Manag Care Spec Pharm. 2021;27:1613–7.

    PubMed  Google Scholar 

  21. Wang Y. An insider’s perspective on FDA approval of aducanumab. Alzheimers Dement (N Y). 2023;9: e12382.

    Article  PubMed  Google Scholar 

  22. Englund H, Sehlin D, Johansson AS, Nilsson LN, Gellerfors P, Paulie S, et al. Sensitive ELISA detection of amyloid-beta protofibrils in biological samples. J Neurochem. 2007;103:334–45.

    CAS  PubMed  Google Scholar 

  23. Lord A, Gumucio A, Englund H, Sehlin D, Sundquist VS, Soderberg L, et al. An amyloid-beta protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2009;36:425–34.

    Article  CAS  PubMed  Google Scholar 

  24. Tucker S, Moller C, Tegerstedt K, Lord A, Laudon H, Sjodahl J, et al. The murine version of BAN2401 (mAb158) selectively reduces amyloid-beta protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimers Dis. 2015;43:575–88.

    Article  CAS  PubMed  Google Scholar 

  25. Sollvander S, Nikitidou E, Gallasch L, Zysk M, Soderberg L, Sehlin D, et al. The Abeta protofibril selective antibody mAb158 prevents accumulation of Abeta in astrocytes and rescues neurons from Abeta-induced cell death. J Neuroinflammation. 2018;15:98.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lecanemab Sweeps Up Toxic Aβ Protofibrils, Catches Eyes of Trialists. ALZFORUM: ALZFORUM, 2021.

  27. Short Aβ Fibrils Easily Isolated from Alzheimer's Brain Fluid. ALZFORUM: ALZFORUM, 2022.

  28. Johannesson M, Sahlin C, Soderberg L, Basun H, Falting J, Moller C, et al. Elevated soluble amyloid beta protofibrils in Down syndrome and Alzheimer’s disease. Mol Cell Neurosci. 2021;114: 103641.

    Article  CAS  PubMed  Google Scholar 

  29. Rofo F, Buijs J, Falk R, Honek K, Lannfelt L, Lilja AM, et al. Novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta. Transl Neurodegener. 2021;10:38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G, et al. Safety and tolerability of BAN2401–a clinical study in Alzheimer’s disease with a protofibril selective Abeta antibody. Alzheimers Res Ther. 2016;8:14.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Abeta protofibril antibody. Alzheimers Res Ther. 2021;13:80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by The Royal Society UK (No. IEC\NSFC\201094) and Alzheimer's Research UK (No. 112336), to JZ.

Author information

Authors and Affiliations

  1. Institute of Biomedical and Clinical Sciences, Medical School, Faculty of Health and Life Sciences, University of Exeter, Hatherly Laboratories, Streatham Campus, Exeter, EX4 4PS, UK

    Jinwei Zhang

  2. State Key Laboratory of Chemical Biology, Research Center of Chemical Kinomics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China

    Jinwei Zhang

Authors
  1. Jinwei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JZ: wrote the main manuscript text and prepared all figures. The author reviewed the manuscript.

Corresponding author

Correspondence to Jinwei Zhang.

Ethics declarations

Conflict of interest

None declared.

Additional information

Responsible Editor: John Di Battista.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, J. Commentaries: Lecanemab: pioneering the way as the first approved drug for Alzheimer’s disease treatment. Inflamm. Res. 72, 1873–1876 (2023). https://doi.org/10.1007/s00011-023-01788-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-023-01788-y

Keywords

Search

Navigation