ARIA in patients treated with lecanemab (BAN2401) in a phase 2 study in early Alzheimer's disease.

Autor: Honig LS; Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Irving Medical Center New York New York USA., Barakos J; California Pacific Medical Center San Francisco California USA.; Clario Inc. San Mateo California USA., Dhadda S; Alzheimer's Disease and Brain Health Eisai Inc. Nutley New Jersey USA., Kanekiyo M; Alzheimer's Disease and Brain Health Eisai Inc. Nutley New Jersey USA., Reyderman L; Alzheimer's Disease and Brain Health Eisai Inc. Nutley New Jersey USA., Irizarry M; Alzheimer's Disease and Brain Health Eisai Inc. Nutley New Jersey USA., Kramer LD; Alzheimer's Disease and Brain Health Eisai Inc. Nutley New Jersey USA., Swanson CJ; Alzheimer's Disease and Brain Health Eisai Inc. Nutley New Jersey USA., Sabbagh M; Creighton University Phoenix Arizona USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (New York, N. Y.) [Alzheimers Dement (N Y)] 2023 Mar 20; Vol. 9 (1), pp. e12377. Date of Electronic Publication: 2023 Mar 20 (Print Publication: 2023).
DOI: 10.1002/trc2.12377
Abstrakt: Introduction: Lecanemab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that preferentially targets soluble aggregated Aβ species (protofibrils) with activity at amyloid plaques. Amyloid-related imaging abnormalities (ARIA) profiles appear to differ for various anti-amyloid antibodies. Here, we present ARIA data from a large phase 2 lecanemab trial (Study 201) in early Alzheimer's disease.
Methods: Study 201 trial was double-blind, placebo-controlled (core) with an open-label extension (OLE). Observed ARIA events were summarized and modeled via Kaplan-Meier graphs. An exposure response model was developed.
Results: In the phase 2 core and OLE, there was a low incidence of ARIA-E (<10%), with <3% symptomatic cases. ARIA-E was generally asymptomatic, mild-to-moderate in severity, and occurred early (<3 months). ARIA-E was correlated with maximum lecanemab serum concentration and incidence was higher in apolipoprotein E4 (ApoE4) homozygous carriers. ARIA-H and ARIA-E occurred with similar frequency in core and OLE.
Discussion: Lecanemab can be administered without titration with modest incidence of ARIA.
Competing Interests: Lawrence S. Honig; Research Funding from Abbive, Acumen, Alector, Biogen, Eisai, Genentech, Janssen/J&J, Roche, Transposon, UCB, Vaccinex.; Consulting fees from Alector, Biogen, Cortexyme, Eisai, Medscape, Prevail.; Jerome Barakos; Speaker fees from Biogen. Employee of Clario.; Shobha Dhadda, Michio Kanekiyo, Larisa Reyderman, Michael Irizarry, Lynn D. Kramer, and Chad J. Swanson; Authors are employees of Eisai Inc.; Marwan Noel Sabbagh MD; Ownership interest (Stock or stock options): NeuroTau, uMethod Health, Versanum, Athira, TransDermix, Seq BioMarque, NeuroReserve, Cortexyme/Quince Therapeutics, Lighthouse Therapeutics; Consulting: Alzheon, Biogen, Roche‐Genentech, Eisai, KeifeRx, Lilly, Synaptogenix, NeuroTherapia, T3D, Signant Health, Novo Nordisk; Royalties: Humanix; Board of Director:EIP Pharma. Author disclosures are available in the supporting information.
(© 2023 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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