The N-MOmentum study (NCT02200770) is the only phase 3 clinical trial that collected MRI imaging and integrated the data into its attack adjudication criteria for neuromyelitis optica spectrum disorder (NMOSD). The MRI data from the trial showed that inebilizumab (Uplizna, Horizon Therapeutics), an anti-CD19 B-cell depleting antibody, reduced the formation of subclinical optic nerve lesions in patients with NMOSD. These findings were presented during the 49th annual meeting of the North American Neuro-Ophthalmology Society (NANOS) March 11-16, 2023, in Orlando, Florida, and provides a better understanding of inebilizumab’s effect on subclinical lesions.1
Additional findings from the trial evaluating the relationship between peripheral blood B-cell subsets and aquaporin-4 (AQP4) immunoglobulin G (IgG) titers and NMOSD attacks were presented as an abstract at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts. Results from the study showed that increased levels of B-cell subsets at time of attack were observed for those on placebo, but not in the inebilizumab-treated group, particularly in the plasma cell subset.
Jeffrey Bennett, MD, PhD, professor of neurology at the University of Colorado, sat down in an interview with NeurologyLive® to discuss the findings from the MRI imaging analysis of patients from the N-MOmentum trial, as well as how the efficacy and safety of inebilizumab compares to other treatments for NMOSD. Bennett, senior author of the study, also spoke about the future plans for inebilizumab in clinical trials and how the treatment has changed the landscape of care for patients.
NeurologyLive®: What were the major highlights of the study?
Jeffrey Bennett, MD, PhD: A high proportion of participants experienced subclinical gadolinium-enhancing (Gd+) T1-1 weighted (Gad+T1) optic nerve (ON) MRI lesions without new symptoms at the end of the randomized control period (RCP). These asymptomatic Gad+T1 lesions were shorter (median length 6 mm) than lesions associated with an optic neuritis attack (15 mm, P <.001) and did not correlate with future attack risk.
While the rate of total asymptomatic optic nerve MRI findings (Gad+T1 and new or enlarging T2-weighted lesions) were not reduced compared with placebo during the randomized control period, the number of clinical optic neuritis attacks was significantly reduced during this time period. Moreover, the formation of these subclinical MRI lesions reduced with repeated inebilizumab treatment over the course of the open label portion of the trial. The relationship of these subclinical ON MRI findings with disease activity will need to be elucidated in future studies.
Can you explain the significance of the MRI findings?
The N-MOmentum trial is the only phase 3 clinical trial in NMOSD that collected MRI data and integrated MRI into its attack adjudication criteria. This new post-hoc analysis illustrates that subclinical MRI activity may be more prevalent in patients with NMOSD than previously appreciated. Reduction of subclinical Gad+T1 MRI lesions with continued inebilizumab treatment suggests that inebilizumab directly or indirectly improves blood-brain barrier integrity.
The use of MRI in the N-MOmentum trial has helped quantify the most visible effects of NMOSD attacks, as well as changes at the subclinical level that may assist in monitoring disease activity over time.
How does inebilizumab compare to other treatments for NMOSD in terms of efficacy and safety?
Inebilizumab is an FDA-approved treatment option for adult patients with NMOSD who are anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+), and the only approved treatment that targets B-cells, including plasmablasts and plasma calls. Inebilizumab binds directly to CD19 on the surface of B cells, from early development through to the stage of antibody secretion.
In the N-MOmentum trial, which is the largest clinical trial conducted in NMOSD to date, inebilizumab demonstrated a significant reduction in the risk of an NMOSD attack with only two infusions per year, following the initial loading doses. Additionally, 89% of patients in the AQP4-IgG+ group remained attack free during the 6-month period post-treatment and more than 83% of patients who stayed on treatment for more than 4 years remained attack free for at least 4 years.
Inebilizumab also has a very good safety profile in patients with NMOSD, with serious adverse effects being lower with inebilizumab (4% of patients) compared with placebo (10%). No head-to-head clinical studies have been conducted to compare the efficacy and safety of inebilizumab to other biologic treatments.
Can you discuss any future plans for inebilizumab, such as potential expansion in further clinical trials?
Inebilizumab is being studied in a phase 3 trial for the prevention of flare in patients with IgG4-related disease as well as a phase 3 trial for improving outcomes in patients with myasthenia gravis.
How does inebilizumab change the landscape of care for patients with NMOSD?
Inebilizumab and its mechanism have made a compelling addition to the treatment landscape for NMOSD, as it targets and destroys B cells at nearly all stages of their life cycle. This is important because anti-APQ4 autoantibodies are produced by plasmablasts and plasma cells, which are central to NMOSD disease pathogenesis and not directly targeted by anti-CD20 B-cell-depleting therapies. Plasmablasts, and some plasma cells, express CD19, and their depletion may lessen inflammatory lesion formation and astrocyte damage (which present clinically as NMOSD attacks).
Inebilizumab is also the only approved NMOSD therapy with a maintenance schedule of just 2 doses per year after the initial two start-up doses.
What else do you think is important to address from the findings?
The findings helped deepen our understanding of inebilizumab not just on NMOSD attacks, but also on asymptomatic activity. Although it’s encouraging to see that continued use of inebilizumab decreased the rate of subclinical ON enhancement over time, future studies will need to be conducted to offer additional clarity on the significance of these findings and how they may contribute to overall disease burden.
Transcript edited for clarity.