Uplizna Shows Significant Efficacy, Safety Treating Generalized Myasthenia Gravis in Phase III MINT Trial

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Findings from the Phase III MINT clinical trial (NCT04524273) show that Uplizna (inebilizumab) produced significant short-term clinical improvements in patient- and clinician-assessed outcomes with a tolerable safety profile among adults with generalized myasthenia gravis (gMG). These findings, published by The New England Journal of Medicine, indicate that Uplizna could be an effective treatment option for B-cell depletion, pending long-term data, according to the trial investigators.^1,2

“Treatment with [Uplizna], as compared with placebo, yielded clinical improvement in patient-assessed activities of daily living and in clinician-assessed disease severity in a combined population of participants with acetylcholine receptor antibody–positive and muscle-specific kinase antibody–positive [gMG] in this phase 3 trial, which included a prespecified glucocorticoid taper,” the study authors wrote. “Additional data are needed to confirm the long-term clinical benefits and safety of [Uplizna] in the treatment of patients with [gMG].”¹

Uplizna is a humanized, afucosylated IgG1 kappa monoclonal antibody that was designed to target CD19 to induce rapid, deep, and durable B-cell depletion. The medication is currently indicated to treat neuromyelitis optica spectrum disorder in adults who are anti-aquaporin-4 antibody positive.

“CD19 (rather than CD20) expression is apparent in early B-cell development. When B cells mature into plasmablastsand plasma cells, they lose some CD20 expression while retaining CD19 expression,” the study authors wrote. “For this reason, therapies that target CD19 (rather than CD20) might have therapeutic relevance to both acetylcholine receptor antibody–positive and muscle-specific kinase antibody–positive [gMG] on the basis of the depletion of relevant pathogenic antibody-secreting cells. [Uplizna], a humanized, afucosylated IgG1 kappa monoclonal antibody administered every 6 months, targets and depletes CD19+ B cells, including myasthenia gravis–specific autoantibody-producing plasmablasts and plasma cells.”¹

Trial Design

The double-blind, randomized, placebo-controlled trial enrolled 238 patients with gMG who had anti–acetylcholine receptor antibodies or anti–muscle-specific kinase antibodies. Participants were randomly assigned in a 1:1 ratio to receive Uplizna administered intravenously at a dose of 300 mg on days one and 15 for all patients in the trial, as well as on day 183 for acetylcholine receptor antibody–positive patients; or matching placebo for 52 weeks in acetylcholine receptor antibody–positive patients or 26 weeks in muscle-specific kinase antibody–positive patients. Beginning at week four, treatment with glucocorticoids was tapered to a target dose of 5 mg per day by week 24. 

The trial’s primary endpoint was change from baseline in Myasthenia Gravis Activities of Daily Living scale (MG-ADL) score at week 26 in the combined cohorts of patients who are acetylcholine receptor antibody–positive and muscle-specific kinase antibody–positive. A key secondary endpoint was change from baseline in Quantitative Myasthenia Gravis scale (QMG) score at week 26 in the combined patient population.

Results show that patients administered Uplizna experienced a higher decrease in MG-ADL score compared with the placebo cohort at week 26 (least-squares mean change, −4.2 vs. −2.2; adjusted difference, −1.9; 95% confidence interval [CI], −2.9 to −1.0; P<0.001). Patients in the Uplizna cohort also experienced a higher decrease in QMG score compared to the placebo cohort (least-squares mean change, −4.8 vs. −2.3; adjusted difference, −2.5; 95% CI, −3.8 to −1.2; P<0.001).

In terms of safety, both cohorts experienced similar incidence of treatment-related adverse events (AEs); however, a higher number of unique AEs were reported in the Uplizna cohort. The most frequently reported AEs among patients administered Uplizna were headache, cough, nasopharyngitis, infusion-related reactions, and urinary tract infections. Uplizna was not associated with a higher incidence of serious AEs.

“Our trial benefited from a large, diverse sample that is broadly representative of the overall population of patients with [gMG],” the study authors wrote. “The glucocorticoid-tapering plan of MINT was designed to address the broadly accepted clinical practice of minimizing long-term glucocorticoid exposure during treatment of patients with [gMG], given that such exposure has negative side effects and may confound measurement of the efficacy of other therapies. Not only did participants in this trial undergo successful tapering of glucocorticoids, but participants in the [Uplizna] group showed clinical improvements as compared with the placebo group.”¹

References

1. Nowak R., et al. A Phase 3 Trial of Inebilizumab in Generalized Myasthenia Gravis. N Engl J Med 2025. DOI: 10.1056/NEJMoa2501561.

2. Myasthenia Gravis Inebilizumab Trial (MINT). ClinicalTrials.gov. Updated February 20, 2025. Accessed April 17, 2025. https://clinicaltrials.gov/study/NCT04524273