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. 2023 Mar 20;9(1):e12377.
doi: 10.1002/trc2.12377. eCollection 2023 Jan-Mar.

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

Lawrence S Honig  1 , Jerome Barakos  2   3 , Shobha Dhadda  4 , Michio Kanekiyo  4 , Larisa Reyderman  4 , Michael Irizarry  4 , Lynn D Kramer  4 , Chad J Swanson  4 , Marwan Sabbagh  5
Affiliations

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

Lawrence S Honig et al. Alzheimers Dement (N Y). .

Abstract

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.

Keywords: ARIA; Alzheimer's disease; anti‐amyloid; exposure response modeling; lecanemab.

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Conflict of interest statement

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.

Figures

FIGURE 1
FIGURE 1
Kaplan‐Meier estimate of ARIA‐E risk in subjects receiving 10 mg/kg biweekly Lecanemab in the Study 201 Core for the (A) overall population and the (B) ApoE4 carriers subgroup.
FIGURE 2
FIGURE 2
Kaplan‐Meier estimate of ARIA‐E risk in subjects receiving 10 mg/kg biweekly lecanemab in the Study 201 OLE for the (A) overall ole population and the (B) ApoE4 carriers subgroup.
FIGURE 3
FIGURE 3
Model‐predicted and observed ARIA‐E versus lecanemab Css,max for ApoE4 subgroups.
FIGURE 4
FIGURE 4
Observed ARIA‐E in OLE versus simulated using PK/PD model in lecanemab‐treated (any dose) subjects from the core study.
See this image and copyright information in PMC

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