Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces pathogenic autoantibody and total IgG levels through neonatal Fc receptor blockade. Patients with anti-acetylcholine receptor antibody–negative (AChR-Ab–) generalized myasthenia gravis (gMG) comprise 15%-20% of the gMG population and have limited approved treatment options owing to historical exclusion from clinical trials.
Objectives: To evaluate long-term safety and efficacy of efgartigimod in AChR-Ab– patients using data pooled from the phase 3 ADAPT study and ongoing long-term extension, ADAPT+.
Methods: ADAPT evaluated the safety and efficacy of efgartigimod versus placebo in AChR-Ab+ (n=129) and Ab– (n=38; 6 MuSK-Ab+) patients with gMG. This integrated analysis includes data from 37 AChR-Ab– patients (5 MuSK-Ab+) who received ≥1 dose of efgartigimod in ADAPT/ADAPT+ through October 2020 (median[range] follow-up: 453[85-721] days). Efficacy was assessed using Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Responder status was defined as ≥2-point (MG-ADL) and ≥3-point (QMG) improvement for ≥4 consecutive weeks (with first improvement ≤1 week after last infusion).
Results: Among AChR-Ab– patients in ADAPT, 68.4% (13/19) of patients treated with efgartigimod were MG-ADL responders (placebo, 63.2% [12/19]), and 52.6% (10/19) were QMG responders (placebo, 36.8% [7/19]) in cycle 1. In cycle 1 of the integrated analysis, AChR-Ab– patients (including 18 placebo patients who received efgartigimod during ADAPT+) improved from cycle baseline in both MG-ADL (≥2- to ≥7-point improvements of 87.9%–35.1%, respectively) and QMG (≥3- to ≥9-point improvements of 86.5%–27.0%). Consistently similar improvements in both efficacy measures occurred through at least 7 cycles. Safety and efficacy outcomes in AChR-Ab– patients were similar to those observed in AChR-Ab+ patients.
Conclusion: Long-term treatment (median >1 year) with efgartigimod was associated with clinically meaningful improvements in MG-ADL/QMG scores in AChR-Ab– patients in ADAPT/ADAPT+.