Long-term safety, tolerability, and efficacy of efgartigimod in patients with generalized myasthenia gravis: Concluding analyses from the ADAPT+ study

Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total IgG levels (including pathogenic autoantibodies) through neonatal Fc receptor blockade. ADAPT, a 26-week, global, randomized, controlled, phase 3 trial, evaluated efgartigimod in adult patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT were eligible to enroll in the ADAPT+ open-label extension study. Efgartigimod (10 mg/kg IV) was administered in cycles of once-weekly infusions for 4 weeks, with subsequent cycles initiated based on clinical evaluation. Primary objectives in ADAPT+ were to evaluate long-term safety and tolerability of efgartigimod in adult patients with gMG. Long-term efficacy was assessed using the Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Ninety percent of patients (151/167) from ADAPT entered ADAPT+, and 145 (111 anti-AChR-Ab+/34 anti-AChR-Ab-) received ≥1 cycle as of January 2022. With 229 patient-years of follow-up (mean duration per patient: 610 days), the most common adverse events were headache (25%), COVID-19 infection (16%), nasopharyngitis (14%), diarrhea (10%), and urinary tract infection (9%), which were mostly mild-moderate and did not increase in frequency in subsequent cycles. AChR-Ab+ patients with ≥1 year of follow-up across ADAPT/ADAPT+ (n=103) received a median (range) 5.2 (0.5-7.5) cycles per year. All anti-AChR-Ab+ patients (n=111), showed consistent and repeatable improvements in MG-ADL (mean [SE] change week 3 of cycle 1: -5.0 [0.33]; ≤11 cycles) and QMG (-4.7 [0.41]; ≤7 cycles) during each cycle, mirroring repeatable reductions in total IgG (mean [SE] reduction; ≤7 cycles: -55.9% [1.15]) and anti-AChR autoantibody levels (-56.1% [1.43]). Similar results were seen in AChR-Ab- patients. These analyses suggest long-term efgartigimod treatment is well tolerated and results in consistent, repeatable improvements in clinical outcomes (MG-ADL and QMG) in adult patients with gMG. Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total IgG levels (including pathogenic autoantibodies) through neonatal Fc receptor blockade. ADAPT, a 26-week, global, randomized, controlled, phase 3 trial, evaluated efgartigimod in adult patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT were eligible to enroll in the ADAPT+ open-label extension study. Efgartigimod (10 mg/kg IV) was administered in cycles of once-weekly infusions for 4 weeks, with subsequent cycles initiated based on clinical evaluation. Primary objectives in ADAPT+ were to evaluate long-term safety and tolerability of efgartigimod in adult patients with gMG. Long-term efficacy was assessed using the Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Ninety percent of patients (151/167) from ADAPT entered ADAPT+, and 145 (111 anti-AChR-Ab+/34 anti-AChR-Ab-) received ≥1 cycle as of January 2022. With 229 patient-years of follow-up (mean duration per patient: 610 days), the most common adverse events were headache (25%), COVID-19 infection (16%), nasopharyngitis (14%), diarrhea (10%), and urinary tract infection (9%), which were mostly mild-moderate and did not increase in frequency in subsequent cycles. AChR-Ab+ patients with ≥1 year of follow-up across ADAPT/ADAPT+ (n=103) received a median (range) 5.2 (0.5-7.5) cycles per year. All anti-AChR-Ab+ patients (n=111), showed consistent and repeatable improvements in MG-ADL (mean [SE] change week 3 of cycle 1: -5.0 [0.33]; ≤11 cycles) and QMG (-4.7 [0.41]; ≤7 cycles) during each cycle, mirroring repeatable reductions in total IgG (mean [SE] reduction; ≤7 cycles: -55.9% [1.15]) and anti-AChR autoantibody levels (-56.1% [1.43]). Similar results were seen in AChR-Ab- patients. These analyses suggest long-term efgartigimod treatment is well tolerated and results in consistent, repeatable improvements in clinical outcomes (MG-ADL and QMG) in adult patients with gMG.