Inebilizumab shows benefit in patients with gMG

Treatment with inebilizumab significantly improved generalized myasthenia gravis (gMG) symptoms, as shown by a greater reduction in MG-Activities of Daily Living (MG-ADL) scores, among patients who were acetylcholine receptor antibody-positive (AChR-Ab+) or muscle-specific kinase antibody-positive (MuSK-Ab+), according to the phase III MINT* trial presented at AAN 2025.

The MINT trial met its primary endpoint of achieving a significant reduction in MG-ADL scores at week 26 with inebilizumab compared with placebo in the combined AChR-Ab+ and MuSK-Ab+ populations, said lead author Dr Richard Nowak from Yale School of Medicine in New Haven, Connecticut, US.

This phase III, double-blind trial analysed 238 adults (mean age 47.5 years, 61 percent female) diagnosed with gMG, of whom 190 were AChR-Ab+ and 48 were MuSK-Ab+. Participants were randomized in a 1:1 ratio to receive intravenous inebilizumab** or placebo (n=95 each [AChR-Ab+ cohort] and n=24 each [MuSK-Ab+ cohort]).

From week 4, participants on >5 mg of glucocorticoids, specifically prednisone, were tapered down to 5 mg per day by week 24. The MuSK-Ab+ cohort was followed for 26 weeks, while the AChR-Ab+ cohort was followed for up to 52 weeks.

At baseline, the mean MG-ADL score was 9.1 and Quantitative Myasthenia Gravis (QMG) score was 17, with higher scores indicating greater disease activity.

In the combined population, patients who received inebilizumab had significantly reduced MG-ADL scores at week 26 compared with those on placebo (least squares [LS] mean change from baseline, –4.2 vs –2.2; adjusted difference, –1.9; p<0.001). [Nowak, et al, AAN 2025]

Moreover, the QMG score was significantly reduced by 4.8 in the inebilizumab group compared with 2.3 in the placebo group for the combined population (adjusted difference, -2.5; p<0.001).

When antibody subtypes were assessed individually, the AChR-Ab+ cohort treated with inebilizumab vs placebo experienced significant reductions in MG-ADL (LS mean change from baseline, –4.2 vs –2.4; adjusted difference, –1.8; p<0.05) and QMG (LS mean change from baseline, –4.4 vs –2; adjusted difference, –2.5; p<0.05) scores at week 26.

A similar trend was observed in the MuSK-Ab+ cohort, with the inebilizumab group achieving a significant decrease in MG-ADL (LS mean change from baseline, –3.9 vs –1.7; adjusted difference, –2.2; p<0.05) and QMG (LS mean change from baseline, –5.2 vs –3; adjusted difference, –2.3; p=0.13) scores, though the latter finding did not reach statistical significance.

In terms of safety, the rates of treatment-emergent adverse events were comparable between the inebilizumab and placebo groups (80.7 percent vs 73.1 percent).

The overall safety findings were consistent with the known safety profile of inebilizumab, Nowak noted.

In this first phase III trial, “treatment with inebilizumab, 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 AChR-Ab+ and MuSK-Ab+ gMG,” said the researchers. [N Engl J Med 2025;doi:10.1056/NEJMoa2501561]

AChR-Ab+ cohort shows sustained benefit at week 52

In another phase III study of MINT, AChR-Ab+ gMG patients treated with inebilizumab showed a continued improvement in MG-ADL and QMG scores (adjusted difference, –2.8; p=0.001 and –4.3; p=0.001, respectively), through week 52 compared with placebo. [Nowak, et al, AAN 2025]

Significantly more inebilizumab-treated patients also achieved a ≥3-point improvement in MG-ADL (72.3 percent vs 45.2 percent; p<0.001) and QMG (69.2 percent vs 41.6 percent; p<0.001) scores at week 52 than placebo-treated patients.

“Overall, clinically meaningful improvements in MG-ADL and QMG scores were observed in inebilizumab-treated patients with AChR-Ab+ gMG through week 52 with a protocol-specified steroid taper,” Nowak said.

“This prespecified analysis of MINT supports continued improvement and the efficacy of inebilizumab in patients with AChR-Ab+ gMG through week 52,” he added.