Lecanemab

Lecanemab, sold under the brand name Leqembi, is a monoclonal antibody medication used for the treatment of Alzheimer's disease.[1][2] Lecanemab is an amyloid beta-directed antibody.[1] It is given via intravenous infusion.[1]

Lecanemab
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetBeta amyloid
Clinical data
Trade namesLeqembi
Other namesBAN2401, lecanemab-irmb
AHFS/Drugs.comMonograph
License data
Routes of
administration		Intravenous
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6544H10088N1744O2032S46
Molar mass147181.62 g·mol−1

Lecanemab was approved for medical use in the United States in January 2023.[2][3]

Medical uses

Lecanemab is indicated for the treatment of Alzheimer's disease.[2]

Adverse effects

Lecanemab, and other amyloid targeting therapies, are associated with amyloid-related imaging abnormalities (ARIA).[2] According to a phase 3 clinical trial (n=1795), lecanemab has been associated with both ARIA-E (cerebral edema) and ARIA-H (microhaemorrhages, or small haemorrhages, and hemosiderosis) sub-types. In the lecanemab group, the incidence of ARIA-E was 12.6% (7.4% in placebo), and the incidence of ARIA-H was 17.3% (1.7% in placebo). [4]

Mild to moderate infusion-related reactions can also occur.[4]


Pharmacology

Mechanism of action

Lecanemab is a monoclonal antibody consisting of the humanized version[5] of a mouse antibody, mAb158, that recognizes protofibrils and prevents amyloid beta deposition in animal models of Alzheimer's disease.[6]

History

In July 2022, the US Food and Drug Administration (FDA) accepted an application for accelerated approval for lecanemab.[7]

In September 2022, Biogen announced[7][8] positive results from an ongoing phase III clinical trial.[9][10]

In November 2022, it was announced that the drug was a success in clinical trials, and exceeded its goal in reaching primary endpoints.[11]

The efficacy of lecanemab was evaluated in a double-blind, placebo-controlled, parallel-group, dose-finding study of 856 participants with Alzheimer's disease.[2] Treatment was initiated in participants whose disease was in the stage of mild cognitive impairment or mild dementia and who had confirmed presence of amyloid beta pathology.[2] Participants receiving the treatment showed significant dose- and time-dependent reduction of amyloid beta plaque: Those receiving the approved dose of lecanemab, 10 milligrams/kilogram every two weeks, had a statistically significant reduction in brain amyloid plaque from baseline to week 79 compared with those receiving a placebo, who had no reduction of amyloid beta plaque.[2] 

The FDA approved lecanemab in January 2023, via the accelerated approval pathway for the treatment of Alzheimer's disease.[2] The FDA granted the application for lecanemab fast track, priority review, and breakthrough therapy designations.[2] The approval of Leqembi was granted to Eisai R&D Management Co., Ltd.[2]

Society and culture

In January 2023, the FDA granted accelerated approval for lecanemab.[2][12]

Economics

Lecanemab pricing is US$26,500 per year,[13] with an estimated "per-patient societal value" of US$37,600.[14] However, cost-effectiveness analysis by the Institute for Clinical and Economic Review (ICER) concluded that a broad range of $8,900 to $21,500 would be appropriate.[15] According to an estimate by the manufacturer, Eisai, about 85% of eligible early-Alzheimer's patients in the United States are covered by Medicare.[14]

After reviewing the clinical evidence and considering the treatments’ other potential benefits, disadvantages, and contextual considerations noted above, the California Technology Assessment Forum unanimously concluded that lecanemab at its current pricing represents "low" long term value of money.[15] At lecanemab’s current net price, approximately 5% of the 1.4 million US patients eligible for Alzheimer’s disease treatment that targets beta-amyloid could be treated within five years without crossing the ICER potential budget impact threshold of $777 million per year.[15] As a result, ICER issued an access and affordability alert for lecanemab in the management of Alzheimer’s disease. This alert indicates that the health care costs of the treatment might stress the health system in the short term, resulting in the displacement of other services and a rapid increase in insurance costs.[15]

Names

Lecanemab is the international nonproprietary name.[16]

Research

Lecanemab was jointly developed by the companies Eisai and Biogen and is in clinical trials for the treatment of Alzheimer's disease.[17]

It has shown statistically significant but minor progress, with studies suggesting a decrease in cognitive decline in Alzheimer's participants compared with a control group given a placebo instead.[18]

References
  1. "Leqembi- lecanemab injection, solution". DailyMed. 11 January 2023. Archived from the original on 15 January 2023. Retrieved 21 January 2023.
  2. "FDA Grants Accelerated Approval for Alzheimer's Disease Treatment" (Press release). U.S. Food and Drug Administration (FDA). 6 January 2023. Archived from the original on 7 January 2023. Retrieved 7 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  3. "Lecanemab Summary Review" (PDF). Center for Drug Evaluation and Research (CDER). U.S. Food and Drug Administration (FDA). Archived (PDF) from the original on 7 January 2023. Retrieved 7 January 2023.
  4. van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. (January 2023). "Lecanemab in Early Alzheimer's Disease". The New England Journal of Medicine. 388 (1): 9–21. doi:10.1056/NEJMoa2212948. PMID 36449413. S2CID 254094094.
  5. Lannfelt L, Möller C, Basun H, Osswald G, Sehlin D, Satlin A, et al. (2014). "Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease". Alzheimer's Research & Therapy. 6 (2): 16. doi:10.1186/alzrt246. PMC 4054967. PMID 25031633.
  6. Söllvander S, Nikitidou E, Gallasch L, Zyśk M, Söderberg L, Sehlin D, et al. (March 2018). "The Aβ protofibril selective antibody mAb158 prevents accumulation of Aβ in astrocytes and rescues neurons from Aβ-induced cell death". Journal of Neuroinflammation. 15 (1): 98. doi:10.1186/s12974-018-1134-4. PMC 5875007. PMID 29592816.
  7. "Lecanemab Confirmatory Phase 3 Clarity Ad Study Met Primary Endpoint, Showing Highly Statistically Significant Reduction of Clinical Decline in Large Global Clinical Study of 1,795 Participants With Early Alzheimer's Disease" (Press release). Biogen. 27 September 2022. Archived from the original on 27 September 2022. Retrieved 28 September 2022.
  8. Robbins R, Belluck P (27 September 2022). "Alzheimer's Drug Slows Cognitive Decline in Key Study". The New York Times. Archived from the original on 28 September 2022. Retrieved 28 September 2022.
  9. "A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease (Clarity AD)". ClinicalTrials.gov. 11 July 2022. Archived from the original on 28 September 2022. Retrieved 28 September 2022.
  10. "'This looks like the real deal': Are we inching closer to a treatment for Alzheimer's?". The Guardian. 22 November 2022. Archived from the original on 10 January 2023. Retrieved 22 November 2022.
  11. Gallagher J (30 November 2022). "Alzheimer's drug lecanemab hailed as momentous breakthrough". BBC News Online. Archived from the original on 2 December 2022. Retrieved 30 November 2022.
  12. Howard J, Goodman B (6 January 2023). "Alzheimer's drug lecanemab receives accelerated approval amid safety concerns". CNN. Archived from the original on 6 January 2023. Retrieved 11 January 2023.
  13. "Eisai's Approach To U.S. Pricing For Leqembi (Lecanemab), a Treatment For Early Alzheimer's Disease, Sets Forth Our Concept Of "Societal Value Of Medicine" In Relation To "Price Of Medicine"" (Press release). Eisai Inc. 6 January 2023. Archived from the original on 7 January 2023. Retrieved 7 January 2023 – via PR Newswire.
  14. Bell J (6 February 2023). "Eisai gives first glimpse into Alzheimer's drug launch". BiopharmaDive. Archived from the original on 12 February 2023. Retrieved 11 February 2023.
  15. "ICER Publishes Final Evidence Report on Lecanemab for Alzheimer's Disease" (Press release). Institute for Clinical and Economic Review. 17 April 2023. Retrieved 7 May 2023.
  16. World Health Organization (2020). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 84". WHO Drug Information. 34 (3). hdl:10665/340680.
  17. Clinical trial number NCT01767311 for "Study to Evaluate Safety, Tolerability, and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease" at ClinicalTrials.gov
  18. Devlin H (28 September 2022). "Success of experimental Alzheimer's drug hailed as 'historic moment'". The Guardian. Archived from the original on 28 September 2022.

Further reading
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