BACKGROUND
Autoreactive B-cells are central to upstream immunopathogenesis of generalized Myasthenia Gravis (gMG) through the production of autoantibodies. MINT met its primary efficacy endpoint, demonstrating a significant improvement in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at Week-26.
OBJECTIVE
To evaluate the efficacy andpharmacodynamicsof inebilizumab, a monoclonal antibody targeting CD19+ B-cells, in acetylcholine receptor antibody-positive (AChR+) gMG.
METHODS
MINT (NCT04524273), a phase 3 clinical trial in adults with gMG, included a protocol-specified steroid taper. The randomized control period (RCP) was 52-Weeks for the AChR+ cohort and included additional secondary/exploratory endpoints: change from baseline (CFB) in MG-ADL and Quantitative Myasthenia Gravis (QMG) scores at Week-52, CD20+ B-cell count, and anti-drug antibodies (ADA). AChR+ participants were randomized (1:1) to receive 300mg of intravenous inebilizumab/placebo on RCP Day-1, Day-15, and Day-183.
RESULTS
Of 238 randomized participants, 190 were AChR+ (inebilizumab: 95/placebo: 95). MG-ADL score showed improvement with inebilizumab vs. placebo at Week-52 (adjusted difference, −2.8; 95% CI, −3.9 to −1.7; nominal p<0.001). Similarly, CFB in QMG score was greater in the inebilizumab group vs. placebo at Week-52 (adjusted difference, −4.3; 95% CI, −5.9 to −2.8; nominal p<0.001).
CD20+ B-cell counts fell by 93.3% from baseline two weeks after the initial dose and remained low throughout treatment period in the AChR+ subpopulation. ADA prevalence for inebilizumab vs. placebo-treated participants was 4.2% vs. 2.1% in AChR+ subpopulation.
CONCLUSIONS
Inebilizumab leads to targeted depletion of B-cells and provides durable improvement in the AChR+ gMG subpopulation through Week-52.