Lecanemab: The advent of biologicals in Alzheimer's disease, affordability, and clinical relevance

Aswin A. Anil; Aishwarya Laxmi Krishnan; Prashant Chandra; Mazhuvanchery Kesavan Unnikrishnan

doi:10.7324/JAPS.2025.204843

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Abstract

By 2050, Alzheimer's disease (AD) is predicted to affect 115 million people worldwide, ranking it as the fifth most prevalent cause of death globally and one of the main causes of dementia. The pathology of AD, characterized by synaptic loss, chronic inflammation, and the accumulation of amyloid beta (Aβ) plaques and tau neurofibrillary tangles, presents significant challenges for treatment. This review examines the emerging role of lecanemab, a humanized monoclonal antibody (MAb), which targets toxic soluble Aβ protofibrils to mitigate AD's progression. Recent clinical trials have demonstrated lecanemab's potential in slowing cognitive decline in early-stage AD patients, alongside its differential impact based on patient characteristics, particularly the challenge posed by APOE4 homozygotes. The review encompasses a detailed evaluation of lecanemab's Pharmacokinetics, safety profile, and comparative efficacy with other anti-Aβ therapies like aducanumab. The economic burden ($26,500/ annum) associated with lecanemab therapy is another challenge that needs to be addressed. Hence we discussed the economic considerations surrounding lecanemab's pricing, cost-effectiveness, and implications for accessibility. While lecanemab marks a promising advancement in AD therapy, ongoing scrutiny of its long-term benefits and adverse effects is crucial for determining its role within the evolving landscape of AD treatment options.

Keyword: Alzheimer's disease Lecanemab Amyloid β immunotherapy

Citation:

Anil AA, Krishnan AL, Chandra P, Unnikrishnan MK. Lecanemab: The advent of biologicals in Alzheimer's disease, affordability, and clinical relevance. J Appl Pharm Sci. 2024. Online First. http://doi.org/10.7324/JAPS.2025.204843

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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1. Aisen PS, Jimenez-Maggiora GA, Rafii MS, Walter S, Raman R. Early-stage Alzheimer disease: getting trial-ready. Nat Rev Neurol. 2022 Jul;18(7):389-99. https://doi.org/10.1038/s41582-022-00645-6

2. Alzheimer's disease - PubMed [Internet]. [cited 2024 Jan 10]. Available from: https://pubmed.ncbi.nlm.nih.gov/33667416/

3. Ma C, Hong F, Yang S. Amyloidosis in Alzheimer's disease: pathogenicity, etiology, and related therapeutic directions. Molecules. 2022 Feb 11;27(4):1210. https://doi.org/10.3390/molecules27041210

4. Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M. Alzheimer's disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine. 2019 Jul 19;14:5541-54. https://doi.org/10.2147/IJN.S200490

5. Shi M, Chu F, Zhu F, Zhu J. Impact of Anti-amyloid-β Monoclonal Antibodies on the pathology and clinical profile of Alzheimer's disease: a focus on aducanumab and lecanemab. Front Aging Neurosci. 2022;14:870517. https://doi.org/10.3389/fnagi.2022.870517

6. Chopade P, Chopade N, Zhao Z, Mitragotri S, Liao R, Chandran Suja V. Alzheimer's and Parkinson's disease therapies in the clinic. Bioeng Transl Med. 2023;8(1):e10367. https://doi.org/10.1002/btm2.10367

7. Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer's disease. Neuropharmacology. 2021 Jun 1;190:108352. https://doi.org/10.1016/j.neuropharm.2020.108352

8. Liu J, Yang B, Ke J, Li W, Suen WC. Antibody-based drugs and approaches against amyloid-β species for Alzheimer’s disease immunotherapy. Drugs Aging. 2016 Oct;33(10):685-97. https://doi.org/10.1007/s40266-016-0406-x

9. Bittar A, Sengupta U, Kayed R. Prospects for strain-specific immunotherapy in Alzheimer’s disease and tauopathies. NPJ Vaccines. 2018;3:9. https://doi.org/10.1038/s41541-018-0046-8

10. Gklinos P, Papadopoulou M, Stanulovic V, Mitsikostas DD, Papadopoulos D. Monoclonal antibodies as neurological therapeutics. Pharmaceuticals (Basel). 2021 Jan 26;14(2):92. https://doi.org/10.3390/ph14020092

11. Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, et al. Two Phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014 Jan 23;370(4):322-33. https://doi.org/10.1056/NEJMoa1304839

12. Blennow K, Zetterberg H, Rinne JO, Salloway S, Wei J, Black R, et al. Effect of Immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease. Arch Neurol. 2012 Aug 1;69(8):1002-10. https://doi.org/10.1001/archneurol.2012.90

13. Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP, et al. Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Alzheimer’s Dement. 2012 Jul 1;8(4):261-71. https://doi.org/10.1016/j.jalz.2011.09.224

14. Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer’s Disease \| NEJM [Internet]. [cited 2024 Jan 21]. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa1312889

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