A Phase 3 Trial of Inebilizumab in Generalized Myasthenia Gravis

Nowak, Richard J. M.D.
Benatar, Michael M.D., Ph.D.
Ciafaloni, Emma M.D.
Howard, James F. Jr. M.D.
Leite, Isabel M. M.D.
Utsugisawa, Kimiaki M.D., Ph.D.
Vissing, John M.D., Ph.D.
Rojavin, Mikhail Ph.D.
Li, Qing M.D., Ph.D.
Tang, Fengming Ph.D.
Wu, Yanping Ph.D.
Rampal, Nishi M.D.
Cheng, Sue M.D., Ph.D.

^¹Yale University, New Haven, CT
^²University of Miami Miller School of Medicine, Miami
^³University of Rochester, Rochester, NY
^⁴University of North Carolina, Chapel Hill
^⁵University of Oxford, Oxford, United Kingdom
^⁶Hanamaki General Hospital, Hanamaki, Japan
^⁷Rigshospitalet, University of Copenhagen, Copenhagen
^⁸Amgen, Thousand Oaks, CA

Dr. Nowak can be contacted at [email protected] or at the Department of Neurology, Program for Clinical and Translational Neuromuscular Research, Yale School of Medicine, P.O. Box 208018, New Haven, CT 06520.

^*A complete list of the MINT investigators is provided in the Supplementary Appendix, available at NEJM.org.

This article was published on April 8, 2025, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Supported by Amgen.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank the participants, their families, and the trial site personnel, whose dedication to contributing to science made this trial possible; Yun Li for statistical support; and Hilary Durbano (Red Nucleus) for medical writing and editorial support with an earlier version of the manuscript.

New England Journal of Medicine 392(23):p 2309-2320, June 19, 2025. | DOI: 10.1056/NEJMoa2501561

Abstract

Background

Autoimmune generalized myasthenia gravis is a disease that manifests with fluctuating muscle weakness. Inebilizumab is a monoclonal antibody that depletes CD19+ B cells, which are central to disease pathogenesis.

Methods

In this phase 3, double-blind, randomized, placebo-controlled trial, we enrolled participants with myasthenia gravis who had anti-acetylcholine receptor antibodies or anti-muscle-specific kinase antibodies. Participants were randomly assigned, in a 1:1 ratio, to receive intravenous inebilizumab (300 mg administered on days 1 and 15 for all, and additionally on day 183 for participants who were acetylcholine receptor antibody-positive) or matching placebo for 52 weeks (in participants who were acetylcholine receptor antibody-positive) or 26 weeks (in those who were muscle-specific kinase antibody-positive). Glucocorticoid therapy was tapered, starting at week 4, to a target of 5 mg per day by week 24. The primary end point was the change from baseline in the score on the Myasthenia Gravis Activities of Daily Living scale (MG-ADL; scores range from 0 to 24, with higher scores indicating greater disease activity) at week 26 in the combined acetylcholine receptor antibody-positive and muscle-specific kinase antibody-positive trial populations. A key secondary end point was the change from baseline in the score on the Quantitative Myasthenia Gravis scale (QMG; scores range from 0 to 39, with higher scores indicating greater disease activity) at week 26 in the combined population. Safety was assessed.

Results

A total of 238 participants underwent randomization (119 per group). Participants who received inebilizumab had a greater reduction in the MG-ADL score than those who received placebo (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) at week 26. Participants who received inebilizumab had a greater reduction in the QMG score than those who received placebo (least-squares mean change, −4.8 vs. −2.3; adjusted difference, −2.5; 95% CI, −3.8 to −1.2; P<0.001). The most common adverse events with inebilizumab were headache, cough, nasopharyngitis, infusion-related reactions, and urinary tract infections. Inebilizumab was not associated with a higher incidence of serious adverse events.

Conclusions

In participants with acetylcholine receptor antibody-positive or muscle-specific kinase antibody-positive generalized myasthenia gravis, inebilizumab improved function and reduced disease severity. (Funded by Amgen; MINT ClinicalTrial.gov number, NCT04524273.)