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28 - Could Lecanemab Offer a Ray of Hope?

Published online by Cambridge University Press:  19 January 2024

Daniel Gibbs
Affiliation:
Emeritus of Oregon Health and Science University
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Summary

In January 2023, researchers from Eisai and its partner Biogen published positive results in a phase 3 trial of the anti-amyloid monoclonal antibody, lecanemab. All research subjects had either mild cognitive impairment or early dementia due to Alzheimer’s disease. The primary endpoint was the Clinical Dementia Rating – Sum of Boxes (CDR-SB). This is a numeric scale used to quantify the severity of symptoms of dementia. It is based on interviews of people living with dementia and their caregivers by qualified professionals who assess cognitive and functional performance in six areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The total score of the six areas is the score of the CDR-SB. After 18 months, those receiving lecanemab had 27% less decline of the CDR-SB compared to those receiving a placebo. This was highly significant statistically (p = 0.00005). Brain swelling (ARIA-E) occurred in 12.3% of subjects, about one third the occurrence rate seen in the aducanumab phase 3 trials. However, participants with two copies of the APOE-4 allele were approximately six times more likely to experience symptomatic ARIA with brain swelling and more than three times more likely to experience ARIA with brain bleeding than APOE-4 noncarriers.

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Publisher: Cambridge University Press
Print publication year: 2024

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References

van Dyck, CH, Swanson, CJ, Aisen, P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med 2023; 388: 921. https://doi.org/10.1056/NEJMoa2212948.CrossRefGoogle ScholarPubMed
Thambisetty, M, Howard, R. Lecanemab and APOE genotyping in clinical practice—navigating uncharted terrainJAMA Neurol 2023; published online March 13. https://doi.org/10.1001/jamaneurol.2023.0207.CrossRefGoogle Scholar
Nilsberth, C, Westlind-Danielsson, A, Eckman, Cet alThe ‘Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Aβ protofibril formationNature Neurosci 2001; 4: 887893. https://doi.org/10.1038/nn0901-887.CrossRefGoogle ScholarPubMed

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