Inebilizumab Significantly Improves Function in Generalized Myasthenia Gravis: Phase 3 MINT Trial
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A phase 3 clinical trial found that inebilizumab, a CD19-targeting antibody that depletes B cells, significantly improved daily functioning and reduced disease severity in adults with generalized myasthenia gravis. In the MINT trial, patients treated with inebilizumab achieved nearly twice the reduction in their daily activities impairment score compared to those on placebo after 26 weeks. Published in the New England Journal of Medicine, these results add inebilizumab to a growing toolkit of therapies targeting the underlying immune drivers of myasthenia gravis.
Abstract
Generalized myasthenia gravis (gMG) is an autoimmune neuromuscular disease in which pathogenic autoantibodies, most commonly targeting the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK), disrupt neuromuscular transmission and cause fluctuating, often disabling weakness of voluntary muscles, including those that control breathing. B cells are central to the pathogenesis of both AChR-positive and MuSK-positive gMG, producing the autoantibodies that drive neuromuscular dysfunction. Inebilizumab is a humanized, afucosylated anti-CD19 monoclonal antibody that depletes a broad population of B cells and antibody-secreting plasmablasts, targeting a wider B-cell spectrum than anti-CD20 therapies.
MINT was a phase 3, randomized, double-blind, placebo-controlled trial enrolling adults with AChR-positive or MuSK-positive gMG. Participants received intravenous inebilizumab (300 mg on days 1 and 15, with an additional dose on day 183 for AChR-positive patients) or matching placebo for 26 weeks. The primary endpoint was change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score.
Participants who received inebilizumab had significantly greater reductions in MG-ADL scores compared to placebo (least-squares mean change: -4.2 vs. -2.2; adjusted difference: -1.9; 95% CI, -2.9 to -1.0; P less than 0.001). The Quantitative Myasthenia Gravis (QMG) score, a key secondary endpoint, also favored inebilizumab (-4.8 vs. -2.3; adjusted difference: -2.5; 95% CI, -3.8 to -1.2; P less than 0.001). The safety profile was acceptable, with the most common adverse events being headache, cough, nasopharyngitis, and infusion-related reactions; rates of serious adverse events were comparable between groups. These results support inebilizumab as an effective B-cell depleting therapy with a distinct mechanism targeting the full CD19-positive B-cell spectrum across gMG subtypes.