2023 American Academy of Neurology Abstract Website

Mamatha Pasnoor¹, Vera Bril², Chafic Karam³, Stojan Peric⁴, Jan De Bleecker⁵, Hiroyuki Murai⁶, Andreas Meisel⁷, Said Beydoun⁸, Tuan Vu⁹, Peter Ulrichts¹⁰, Benjamin Van Hoorick¹⁰, Caroline T'joen¹⁰, Kimiaki Utsugisawa¹¹, Jan Verschuuren¹², Renato Mantegazza¹³, James Howard¹⁴, in collaboration with the ADAPT Investigator Study Group
¹University of Kansas Medical Center, ²Ellen & Martin Prosserman Centre for Neuromuscular Diseases, University Health Network, ³Penn Neuroscience Center, University of Pennsylvania, ⁴Neurology Clinic, Clinical Center of Serbia, University of Belgrade, ⁵Ghent University Hospital, ⁶Department of Neurology, School of Medicine, International University of Health and Welfare, ⁷Charité – Universitätsmedizin Berlin, ⁸Keck School of Medicine, University of Southern California, ⁹Department of Neurology, University of South Florida, Morsani College of Medicine, ¹⁰argenx, ¹¹Department of Neurology, Hanamaki General Hospital, ¹²Department of Neurology, Leiden University Medical Center, ¹³Department of Neuroimmunology and Neuromuscular Diseases, Fondazione Istituto Neurologico Carlo Besta, ¹⁴Department of Neurology, The University of North Carolina

Objective:

To evaluate long-term safety and efficacy of efgartigimod.

Background:

Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total IgG and pathogenic IgG autoantibody levels through neonatal Fc receptor blockade. ADAPT was a 26-week, global, multicenter, randomized, controlled, phase 3 trial evaluating efgartigimod in patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT were eligible to enroll in the ADAPT+ open-label extension study.

Design/Methods:

Efgartigimod (10 mg/kg IV) was administered in cycles of once-weekly infusions for 4 weeks, with subsequent cycles initiated based on clinical evaluation. The primary objective in ADAPT+ was to evaluate long-term safety and tolerability of efgartigimod in patients with gMG. Long-term efficacy was also assessed utilizing Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scales.

Results:

90% of patients (151/167) from ADAPT entered ADAPT+ and 145 (111 anti-AChR-Ab+/34 anti-AChR-Ab-) have received ≥1 cycle as of January 2022. With 217.5 patient-years of follow-up (mean duration per patient: 548 days), the most common adverse events were headache (25%), concomitant COVID-19 infection (15%), nasopharyngitis (14%), diarrhea (10%), and urinary tract infections (9%) which were mostly mild-moderate and did not increase in frequency with subsequent cycles. AChR-Ab+ patients with ≥1 year of follow-up across ADAPT/ADAPT+ (n=95) received a median (range) 5.0 (0.4–7.6) cycles per year. In all anti-AChR-Ab+ patients (n=111), consistent improvements in MG-ADL (mean[SE] change week 3 of cycle 1: -5.0[0.33]; up to 14 cycles) and QMG (-4.7[0.41]; up to 7 cycles) scores were observed during each cycle, mirroring repeatable reductions in total IgG (mean[SE] reduction: -55.9%[1.15]; up to 7 cycles) and anti-AChR autoantibody levels (-56.1%[1.43]; up to 7 cycles).

Conclusions:

These analyses of ADAPT+ suggest long-term efgartigimod treatment is well-tolerated and results in consistent and repeatable reductions in IgG antibody levels and clinical outcomes (MG-ADL and QMG) in patients with gMG.