Long-term Safety, Tolerability, and Efficacy of Efgartigimod in Patients With Generalized Myasthenia Gravis: Interim Results of the ADAPT+ Study
James Howard1, Vera Bril2, Tuan Vu3, Chafic Karam4, Stojan Peric5, Jan De Bleecker6, Hiroyuki Murai7, Andreas Meisel8, Said Beydoun9, Mamatha Pasnoor10, Antonio Guglietta11, Peter Ulrichts11, Caroline T'joen11, Kimiaki Utsugisawa12, Jan Verschuuren13, Renato Mantegazza14
1Department of Neurology, The University of North Carolina, 2Krembil Neuroscience Centre, University Health Network, 3Department of Neurology, University of South Florida, Morsani College of Medicine, 4Penn Neuroscience Center, University of Pennsylvania, 5Neurology Clinic, Clinical Center of Serbia, 6Ghent University Hospital, 7Department of Neurology, School of Medicine, International University of Health and Welfare, 8Charité Universitaetsmedizin Berlin, 9Keck School of Medicine, University of Southern California, 10University of Kansas Medical Center, 11argenx, 12Department of Neurology, Hanamaki General Hospital, 13Department of Neurology, Leiden University Medical Center, 14Department of Neuroimmunology and Neuromuscular Diseases, Fondazione Istituto Neurologico Carlo Besta
Objective:
Evaluate the safety, tolerability, and efficacy of efgartigimod in patients with generalized myasthenia gravis (MG) enrolled in the ADAPT+ long-term extension study.
Background:
Treatment with efgartigimod, a human IgG1 antibody Fc-fragment that blocks neonatal Fc receptor, resulted in clinically meaningful improvement (CMI) in MG-specific outcome measures in the ADAPT study. All patients who completed ADAPT were eligible to enroll in its ongoing open-label, 3-year extension study, ADAPT+.
Design/Methods:
Efgartigimod (EFG), 10 mg/kg, was administered intravenously in cycles of once-weekly infusions for 4 weeks, with subsequent cycles initiated based on predefined criteria. Efficacy was assessed during each cycle utilizing Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scales. 
Results:
Ninety-one percent of ADAPT patients (151/167) entered ADAPT+. As of February 2021, 106 AChR-Ab+ and 33 AChR-Ab– had received at least 1 dose of open-label efgartigimod (including 66 ADAPT placebo [PBO] patients). The mean(SD) study duration was 363(114) days, resulting in 138 patient-years of observation. Similar rates of the most common adverse events (AEs) were seen in the EFG-EFG and PBO-EFG arms: headache (15.1%/30.3%), nasopharyngitis (8.2%/13.6%), and diarrhea (6.8%/10.6%). Five deaths (acute myocardial infarction, COVID-19 pneumonia/septic shock, bacterial pneumonia/MG crisis, malignant lung neoplasm, and unknown [multiple cardiovascular risk factors identified on autopsy]) occurred; none were considered related to efgartigimod by the investigator. AEs were predominantly mild or moderate. CMI was observed in AChR-Ab+ patients during each cycle (up to 10 cycles) at magnitudes comparable to improvements observed at week 3 of cycle 1 (mean[SE] improvements: MG-ADL, –5.1[0.34]; QMG, –4.7[0.41]). Clinical improvements mirrored maximal reductions in total IgG and AChR-Abs across all cycles. Similar results were observed in AChR-Ab– patients. 
Conclusions:
This analysis suggests long-term treatment with efgartigimod was well-tolerated and efficacious, regardless of antibody status. Despite being conducted during the COVID-19 pandemic, before vaccine availability, no new safety signals were identified.