Researchers for a phase III trial found that inebilizumab, a CD19+ B-cell–depleting monoclonal antibody, improved function and reduced disease severity in patients with generalized myasthenia gravis.
The randomized, placebo-controlled Myasthenia Gravis Inebilizumab Trial (MINT) included 238 participants with either acetylcholine receptor antibody–positive or muscle-specific kinase antibody–positive generalized myasthenia gravis (MG). All participants underwent a protocol-specified glucocorticoid taper during treatment.
Key Findings
At 26 weeks, participants who received inebilizumab showed greater improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores compared with placebo.
Inebilizumab also demonstrated significant benefit on the Quantitative Myasthenia Gravis (QMG) score, which was a key secondary endpoint. Specifically, participants who received inebilizumab had a greater reduction in QMG scores than those who received placebo.
According to the researchers, led by Richard J. Nowak, MD, of Yale University, improvements with inebilizumab were observed across multiple outcome measures.
Mechanism and Rationale
Autoimmune MG is characterized by autoreactive B cells that produce pathogenic autoantibodies, which disrupt postsynaptic neuromuscular transmission and cause fluctuating muscle weakness. The trial investigators noted that CD19 is expressed early in B-cell development and remains present in plasmablasts and plasma cells, which may lack CD20 expression. Therefore, targeting CD19+ B cells may be effective in depleting antibody-secreting cells in both acetylcholine receptor antibody–positive and muscle-specific kinase antibody–positive MG.
Trial Design and Population
MINT was conducted at 81 active sites across 18 countries. Eligible participants were at least 18 years old with generalized MG (Myasthenia Gravis Foundation of America classification II, III, or IV), an MG-ADL score of 6 to 10 with more than 50% attributed to nonocular items or an MG-ADL score of at least 11, and a QMG score of at least 11.
Participants were randomized 1:1 to receive intravenous inebilizumab (300 mg on days 1 and 15 for all participants and again on day 183 for those with acetylcholine receptor antibodies) or matching placebo. The treatment period was 52 weeks for participants with acetylcholine receptor antibodies and 26 weeks for those with muscle-specific kinase antibodies.
All participants underwent a protocol-defined glucocorticoid taper beginning at week 4, with the goal of reaching up to 5 mg per day by week 24.
Subgroup Analysis
In the acetylcholine receptor antibody–positive subgroup, inebilizumab was associated with significant improvements in MG-ADL and QMG scores at week 26.
In the muscle-specific kinase antibody–positive subgroup, inebilizumab was associated with significant improvement in MG-ADL scores, while the difference in QMG scores did not reach statistical significance.
Among acetylcholine receptor antibody–positive participants, improvements were sustained through week 52. The treatment difference increased from −1.8 at week 26 to −2.8 at week 52 for MG-ADL scores and from −2.5 to −4.3 for QMG scores.
Safety Profile
Adverse events occurred in 80.7% of participants in the inebilizumab group and 73.1% of those who received placebo. Events that occurred in at least 5% of the inebilizumab group included headache (15.1%), COVID-19 (10.9%), cough (6.7%), nasopharyngitis (6.7%), infusion-related reactions (5.9%), and urinary tract infections (6.7%).
Serious adverse events occurred in 8.4% of participants who received inebilizumab and 13.4% who received placebo. Three deaths were reported: one in the inebilizumab group and two in the placebo group.
Conclusion
In their New England Journal of Medicine study, the researchers concluded that inebilizumab improved patient-assessed activities of daily living and clinician-assessed disease severity compared with placebo in participants with acetylcholine receptor antibody–positive and muscle-specific kinase antibody–positive generalized MG. They noted that further data are needed to confirm the long-term safety and efficacy of inebilizumab.
Disclosures are available with the study