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. 2023 Dec;10(12):2413-2420.
doi: 10.1002/acn3.51911. Epub 2023 Oct 7.

Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of FCGR3A polymorphism

Ho Jin Kim  1 , Orhan Aktas  2 , Kristina R Patterson  3 , Schaun Korff  3 , Amy Kunchok  4 , Jeffrey L Bennett  5 , Brian G Weinshenker  6 , Friedemann Paul  7 , Hans-Peter Hartung  2   8   9   10 , Daniel Cimbora  3 , Michael A Smith  3 , Nanette Mittereder  3 , William A Rees  3 , Dewei She  3 , Bruce A C Cree  11
Affiliations

Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of FCGR3A polymorphism

Ho Jin Kim et al. Ann Clin Transl Neurol. 2023 Dec.

Abstract

Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B-cells, is approved to treat aquaporin 4 (AQP4) IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III-A (FCGR3A) receptors on natural killer cells to maximize antibody-dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG-binding affinity and reduce rituximab (anti-CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab-treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.

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Conflict of interest statement

Ho Jin Kim has received a grant from the National Research Foundation of Korea; consultancy/speaker fees or research support from Alexion, AprilBio, Altos Biologics, Biogen, Celltrion, Daewoong Pharmaceutical, Eisai, GC Pharma, HanAll Biopharma, Handok, Horizon Therapeutics (formerly Viela Bio), Kolon Life Science, MDimune, Merck Serono, Mitsubishi Tanabe Pharma, Novartis, Roche, Sanofi Genzyme, Teva‐Handok, and UCB; and is a co‐editor for the Multiple Sclerosis Journal and an associate editor for the Journal of Clinical Neurology.

Orhan Aktas reports grants from the German Research Foundation (DFG) and the German Ministry of Education and Research (BMBF); personal fees or research support from Alexion, Almirall, Bayer HealthCare, Biogen, Horizon Therapeutics (formerly Viela Bio), Merck Serono, Novartis, Roche, Sanofi, and Teva and has received travel reimbursement from the Guthy‐Jackson Charitable Foundation.

Amy Kunchok has received compensation for consultation and scientific advisory boards for Genentech, Horizon therapeutics, and EMD Serono.

Jeffrey L. Bennett reports payment for study design/consultation from MedImmune; personal fees from AbbVie, Alexion, Antigenomycs, BeiGene, Chugai, Clene Nanomedicine, Genentech, Genzyme, Reistone Bio, Roche, Imcyse, Mitsubishi Tanabe, and TG; grants from Alexion, and the National Institutes of Health. In addition, Dr Bennett has a patent “Compositions and methods for the treatment of neuromyelitis optica.”

Brian G. Weinshenker received payments for serving as chair of attack adjudication committees for clinical trials in NMOSD for Alexion, MedImmune, UCB Biosciences, and Horizon Therapeutics; has consulted with Chugai, Genentech, Horizon Therapeutics, Mitsubishi Tanabe Pharma, Roche Pharmaceuticals and CANbridge; and has a patent for NMO‐IgG for diagnosis of neuromyelitis optica, with royalties paid by Hospices Civils de Lyon, MVZ Labor PD Dr. Volkmann und Kollegen GbR, University of Oxford, and RSR. (updated 27 January 2022).

Friedemann Paul has received research support, speaker honoraria, and travel reimbursement from Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, and Teva; is supported by the German Research Council (DFG Exc 257) and the German Competence Network for Multiple Sclerosis; has received travel reimbursement from the Guthy‐Jackson Charitable Foundation; and serves on the steering committee of the OCTIMS study, sponsored by Novartis.

Hans‐Peter Hartung has received fees for consulting, speaking, and serving on steering committees from Bayer HealthCare, Biogen Idec, Celgene Receptos, CSL Behring, GeNeuro, Genzyme, Horizon Therapeutics (formerly Viela Bio), MedDay, MedImmune, Merck Serono, Novartis, Roche, Sanofi, and TG Therapeutics with approval by the Rector of Heinrich Heine University Düsseldorf.

Kristina R. Patterson, Schaun Korff, Daniel Cimbora, Michael A. Smith, Nanette Mittereder, William A. Rees, and Dewei She are employees of Horizon Therapeutics and own stock.

Bruce A. C. Cree reports personal compensation for consulting from Alexion, Atara, Autobahn, Avotres, Biogen, Boston Pharma, EMD Serono, Gossamer Bio, Hexal/Sandoz, Horizon, Immunic AG, Neuron23, Novartis, Sanofi, Siemens, TG Therapeutics and Therini and received research support from Genentech.

Figures

Figure 1
Figure 1
Effects of long‐term inebilizumab use on CD20+ B‐cell counts and plasma cell gene signature by FCGR3A genotype. (A) Longitudinal CD20+ B‐cell count by FCGR3A genotype. *p < 0.05, **p < 0.01, ***p < 0.001. Statistical significance was assessed using the Mann–Whitney U‐test. (B) Longitudinal CD20+ plasma cell gene signature by FCGR3A genotype. *p < 0.05; **p < 0.01. Statistical significance was assessed using Mann–Whitney U‐test.
See this image and copyright information in PMC

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