Abstract General Information


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


Introduction: Inebilizumab, a humanized, afucosylated IgG1 monoclonal antibody that targets CD19 for efficient B-cell depletion, is approved to treat aquaporin 4 (AQP4) immunoglobulin G positive (IgG+) neuromyelitis optica spectrum disorder (NMOSD). Afucosylated monoclonal antibodies are engineered to enhance affinity for the Fc receptor III-A (FCGR3A) receptors and maximize antibody-dependent cellular cytotoxicity. The F allele of the F176V polymorphism (rs396991) of FCGR3A is associated with decreased IgG binding affinity and reduced efficacy of rituximab in NMOSD. Here we report data for the duration of the N-MOmentum trial.

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

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.

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. There was no 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.




Orhan Aktas, Jeffrey L Bennett, Brian G Weinshenker, Friedemann Paul, Ho Jin Kim, Hans-Peter Hartung, Michael A Smith, William A Rees, Dewei She, Mariana Graf, Bruce A C Cree