The phase III Clarity AD clinical trial of lecanemab, an amyloid-targeting antibody, showed a small clinical benefit in people with Alzheimer disease. However, several questions remain regarding the true clinical relevance, safety and accessibility of lecanemab in this patient population.
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References
van Dyck, C. H. et al. Lecanemab in early Alzheimer’s disease. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2212948 (2022).
Ackley, S. F. et al. Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis. BMJ 372, n156 (2021).
Gleason, A., Ayton, S. & Bush, A. I. Unblinded by the light: amyloid-related imaging abnormalities in Alzheimer’s clinical trials. Eur. J. Neurol. 28, e1 (2021).
Center for Drug Evaluation and Research. Aduhelm (aducanumab) FDA statistical review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022568Orig1s000StatR.pdf (2021).
Andrews, J. S. et al. Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer’s disease clinical trials. Alzheimers Dement. (N.Y.) 5, 354–363 (2019).
Lansdall, C. J. et al. Establishing clinically meaningful change on outcome assessments frequently used in trials of mild cognitive impairment due to Alzheimer’s disease. J. Prev. Alzheimers Dis. https://doi.org/10.14283/jpad.2022.102 (2022).
Piller, C. Second death linked to potential antibody treatment for Alzheimer’s disease. Science https://doi.org/10.1126/science.adf9701 (2022).
Nestor, S. M. et al. Ventricular enlargement as a possible measure of Alzheimer’s disease progression validated using the Alzheimer’s disease neuroimaging initiative database. Brain 131, 2443–2454 (2008).
Silbert, L. C. et al. Changes in premorbid brain volume predict Alzheimer’s disease pathology. Neurology 61, 487–492 (2003).
Canevelli, M. et al. “Real world” eligibility for aducanumab. J. Am. Geriatr. Soc. 69, 2995–2998 (2021).
Acknowledgements
M.T. is a full-time employee at the intramural programme of the National Institute on Aging (Baltimore, MD, USA). R.H. is supported by the National Institute for Health Research University College Hospital London Biomedical Research Centre (London, UK).
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Thambisetty, M., Howard, R. Lecanemab trial in AD brings hope but requires greater clarity. Nat Rev Neurol 19, 132–133 (2023). https://doi.org/10.1038/s41582-022-00768-w
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DOI: https://doi.org/10.1038/s41582-022-00768-w
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