Phase 3 Myasthenia Gravis Inebilizumab Trial (MINT): Efficacy and Safety Results in Patients with Generalized MG

Topic:

Clinical Trials

Poster Number: P360

Author(s):

Richard Nowak, MD, Yale University, Kimiaki Utsugisawa, MD, PhD, Hanamaki General Hospital, Michael Benatar, MD, PhD, University of Miami, Miller School of Medicine, Emma Ciafaloni, MD, University of Rochester, M. Isabel Leite, MD, DPhil, University of Oxford, John Vissing, MD, University of Copenhagen, Fengming Tang, PhD, Amgen Inc., Yanping Wu, PhD, Amgen Inc., Mikhail Rojavin, PhD, Amgen Inc., Sue Cheng, MD, Amgen Inc., James F. Howard Jr., MD, University of North Carolina

OBJECTIVE
To investigate the efficacy and safety of inebilizumab, a monoclonal antibody targeting CD19+ B-cells, in generalized myasthenia gravis (gMG).

BACKGROUND
Autoimmune gMG, a disorder of postsynaptic neuromuscular transmission, characterized by production of antibodies against acetylcholine receptor (AChR+), muscle-specific kinase (MuSK+), and less frequently against other proteins, and where autoreactive B-cells are pivotal in upstream pathogenesis.

DESIGN/METHODS
MINT, a phase 3 clinical study (NCT04524273) was conducted in adult gMG patients and included a protocol-required steroid taper. The complete randomized control period (RCP) was 52-weeks (AChR+ population) and 26-weeks (MuSK+ population). Participants were randomized (1:1) to 300 mg of intravenous inebilizumab or placebo, administered on RCP Day-1 and Day-15 and at Week-26 (AChR+ only). The primary endpoint was the change from baseline in MG-ADL score at Week-26 in the combined population. Key secondary endpoints included change in QMG score from baseline to Week-26 in the combined population, and changes from baseline to Week-26 in MG-ADL and QMG-scores in the AChR+ and MuSK+ populations separately.

RESULTS
Total of 238 patients were randomized: inebilizumab 119 (95 AChR+, 24 MuSK+), placebo 119 (95 AChR+, 24 MuSK+). The primary endpoint was achieved demonstrating a clinically meaningful improvement in MG-ADL score change in the inebilizumab group (-4.2) as compared to placebo (-2.2) at Week-26 [difference, -1.9; 95% CI: -2.9, -1.0; p<0.001]. Key secondary endpoint for the combined population demonstrated greater improvement in the QMG score in the inebilizumab group (-4.8) as compared to placebo (-2.3) at Week-26 [difference, -2.5; 95% CI: -3.8, -1.2; p<0.001]. Adverse events occurred in 80.7% inebilizumab and 73.1% placebo-treated participants. Serious adverse events occurred in 8.4% inebilizumab and 13.4% placebo-treated participants. CONCLUSIONS This study provides evidence that inebilizumab is effective and safe for patients with AChR+ or MuSK+ gMG. Targeting an upstream immunopathogenic mechanism may be an effective tool in reducing disease severity and steroid burden.