Results from a new analysis of the inebilizumab pivotal Phase 2/3 N-MOmentum trial were presented this year at ECTRIMS, indicating a correlation between the depth of B-cell depletion and improved NMOSD patient outcomes. Inebilizumab is the first and only FDA-approved anti-CD19 B-cell-depleting humanized monoclonal antibody for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody positive NMOSD.
“This analysis provides additional evidence that B cells play a central role in NMOSD, and that there is a link between the depth of B cell depletion in the blood and long-term clinical outcomes,” said Jeffrey Bennett, MD, PhD, University of Colorado and study author. “We found that B-cell levels at the end of the 28-week randomized, placebo-controlled period of the N-MOmentum trial were predictive of stable and deep B-cell depletion continuing through long-term exposure.”
The N-MOmentum trial included a randomized-controlled period (RCP) of up to 28 weeks, followed by an optional open-label period (OLP) of at least two years. During the trial, B-cell counts were determined using high-resolution flow cytometry (captured as cells/µL). Disease activity was measured using annualized attack rate (AAR) and the number of new or enlarging T2 lesions in the brain or spine.
Key analysis findings include (P028):
- All participants had B-cell reductions at one week from first treatment.
- At Week 4 of the RCP, median (interquartile range [IQR]) B-cell counts were 2.5 (1.0–7.6) cells/μL in the inebilizumab group and 112.3 (96.3–176.9) cells/μL in the placebo group.
- At Week 156 of the OLP, median (IQR) B-cell count was 0.33 (< LLoQ–1.0) cells/μL with inebilizumab.
- inebilizumab provided sustained B-cell depletion after 2.5 years and decreased NMOSD activity in treated patients, with a 97% reduction in AAR and a 73% reduction in new/enlarging lesions when compared to the placebo group.
- Participants with B-cell counts ≤ 4 cells/μL had persistently deeper B-cell depletion compared with those with B-cell counts > 4 cells/μL
- While all participants saw significant treatment effect, those whose B-cell counts were ≤ 4 cells/µL (n=139/200) at Week 28 had reduced rates of AAR (rate ratio 0.4) and new/enlarging lesions (0.36) versus those with B-cell counts > 4 cells/µL.
These data contribute the mechanistic understanding of NMOSD as a B-cell-mediated disease and the effect of inebilizumab on the underlying disease mechanisms known to have the greatest impact on patient outcomes.
Keep an eye out for Physician’s Weekly’s interview and podcast with study author, Jeffrey Bennett, MD, PhD.
