Abstract Details

Title Inebilizumab Reduces Attack Risk Independent of Low Affinity IgG Fc Region Receptor III-A Gene Polymorphisms in Neuromyelitis Optica Spectrum Disorder

Topic Autoimmune Neurology

Presentation(s) P13 - Poster Session 13 (8:00 AM-9:00 AM)

Poster/Presentation
Number 6-015

Objective

To characterize the relationship between the rs396991 polymorphism and the treatment response in N-MOmentum trial participants.

Background Inebilizumab, a humanized, afucosylated IgG1 monoclonal antibody that targets CD19 for B-cell depletion, is approved to treat aquaporin 4 (AQP4) immunoglobulin G positive (IgG+) neuromyelitis optica spectrum disorder (NMOSD). Afucosylated antibodies are engineered to enhance affinity for Fc receptor III-A (FCGR3A) receptors and maximize antibody-dependent cellular cytotoxicity. The F allele of the F176V polymorphism (rs396991) is associated with decreased IgG binding affinity and reduced efficacy of rituximab in NMOSD. Data from participants with different FCGR3A genotypes were compared for disease severity and response to inebilizumab at timepoints up to ≥4 years.

Design/Methods

N-MOmentum (NCT02200770) was a double-blind, phase 2/3 trial of inebilizumab in adults with NMOSD, with a 28-week randomized controlled period (RCP); (inebilizumab 300 mg or placebo on days 1 and 15) and an optional open-label period (OLP) of ≥2 years. A total of 142 participants (inebilizumab, n=104; placebo, n=38) consented for genotyping via TaqMan qPCR assay.

Results

V-allele carriers (V-allele genotype [V/V or V/F], n=74) and F/F–allele homozygotes (n=68) did not demonstrate a significant difference in baseline demographics or disease duration. Depletion of CD20⁺ B-cells was similar in V allele vs F/F allele participants (0.6 (0.1–3.2) vs 1.3 (0.5–4.2) cells/µL at end of RCP) and was sustained in both groups throughout the duration of the study. We did not find any difference in risk of relapse (OR 0.94 (0.39, 2.24)) or Expanded Disability Status Scale worsening (OR: 1.55 (0.54, 4.70)) in V vs F/F allele participants. Annualized attack rates (Standard Error of the Mean [SEM]) for patients on inebilizumab treatment were V/V 0.00 (0.00), V/F 0.10 (0.04), and F/F 0.06 (0.03).

Conclusions Inebilizumab treated participants in the N-MOmentum trial did not demonstrate differences in clinical outcomes between those with F and V allele genotypes.

Authors/Disclosures
Brian G. Weinshenker, MD, FAAN (University of Virginia Health System) PRESENTER	Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CANbridge Pharmaceuticals. Dr. Weinshenker has received personal compensation in the range of $0-$499 for serving as a Consultant for CALIBR. Dr. Weinshenker has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Group (Chugai, Genentech, Roche). Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharmaceuticals. Dr. Weinshenker has received research support from Guthy Jackson Charitable Foundation. Dr. Weinshenker has received intellectual property interests from a discovery or technology relating to health care.
Jeffrey L. Bennett, MD, PhD, FAAN (University of Colorado School of Medicine)	Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immpact Bio. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Chugai. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Beigene. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MIAC. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CorEvitas. Dr. Bennett has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Alexion. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Vindico. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Touch IME. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Efficient LLC. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Pavich. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Marie Bush. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Marks Gray. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Knight, Nicastro, MacKay. The institution of Dr. Bennett has received research support from Alexion. The institution of Dr. Bennett has received research support from Genentech. Dr. Bennett has received intellectual property interests from a discovery or technology relating to health care. Dr. Bennett has received publishing royalties from a publication relating to health care.
Bruce A. Cree, MD, PhD, MAS, FAAN (UCSF, Multiple Sclerosis Center)	The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. The institution of Dr. Cree has received research support from Kyverna. Dr. Cree has received publishing royalties from a publication relating to health care.
Friedemann Paul (Charite Universitatsmedizin in Berlin)	Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hoffmann-La Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol-Myers Squibb GmbH & Co. KGaA (BMS. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics GmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Paul has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for F&U Confirm. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb GesmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MICE Service. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for VINDICO medical education. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Beijing Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sandoz Internation GmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Thailand. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche . Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology, Neuroimmunology&Neuroinflammation.
Ho Jin Kim, MD (National Cancer Center)	Dr. Kim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Altos Biologics, AstraZeneca, Biogen, Daewoong Pharmaceutical, Kaigene, Kolon Life Science, MDimune, Roche, and Sanofi. Dr. Kim has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion, AstraZeneca, Eisai, GC Pharma, Merck, Mitsubishi Tanabe Pharma, and Roche. Dr. Kim has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Multiple Sclerosis Journal, Journal of Clinical Neurology.
Hans-Peter Hartung, MD, FAAN (Heinrich Heine University Medical Faculty)	Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology.
Kristina R. Patterson, MD, PhD (Horizon Therapeutics)	Dr. Patterson has received personal compensation for serving as an employee of Amgen. Dr. Patterson has stock in Amgen.
	No disclosure on file
William Rees	William Rees has received personal compensation for serving as an employee of Horizon Therapeutics. William Rees has received personal compensation for serving as an employee of Viela Bio. William Rees has received stock or an ownership interest from Horizon Therapeutics. William Rees has received stock or an ownership interest from Viela Bio. William Rees has received intellectual property interests from a discovery or technology relating to health care. William Rees has received intellectual property interests from a discovery or technology relating to health care.
Dewei She	No disclosure on file
Orhan Aktas, MD (Neurologische Klinik)	Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen/Horizon. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubish Tanake. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AstraZeneca. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen/Horizon. The institution of Dr. Aktas has received research support from German Research Foundation. The institution of Dr. Aktas has received research support from German Ministry of Science. The institution of Dr. Aktas has received research support from Neuromyelitis optica Study Group (NEMOS).

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