Long-term Safety, Tolerability, and Efficacy of Subcutaneous Efgartigimod PH20 in Participants with Generalized Myasthenia Gravis: Interim Results of the ADAPT-SC+ Study
James Howard1, Yuebing Li2, Tuan Vu3, Denis Korobko4, Sophie Steeland5, Benjamin Van Hoorick5, Jana Podhorna5, Moana Hodari5, Kimiaki Utsugisawa6, Francesco Sacca7, Heinz Wiendl8, Jan De Bleecker9, Renato Mantegazza10
1Department of Neurology, The University of North Carolina, Chapel Hill, North Carolina, 2Cleveland Clinic, Cleveland, Ohio, 3Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, Florida, 4State Budgetary Healthcare Institution of Novosibirsk Region "State Novosibirsk Regional Clinical Hospital," Novosibirsk, Russia, 5argenx, Ghent, Belgium, 6Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan, 7NRSO Department, Federico II University of Naples, Naples, Italy, 8Department of Neurology, University of Münster, Münster, Germany, 9Ghent University Hospital, Ghent, Belgium, 10Department of Neuroimmunology and Neuromuscular Diseases, Fondazione Istituto Neurologico Carlo Besta, Milan, Italy
Objective:

Evaluate long-term safety, tolerability, and efficacy of subcutaneous (SC) efgartigimod PH20 (coformulated with recombinant human hyaluronidase PH20) in participants with generalized myasthenia gravis (gMG) enrolled in the ADAPT-SC+ open-label extension (OLE) study.

Background:

In the ADAPT-SC study, efgartigimod PH20 SC was shown to have noninferior total IgG reduction to efgartigimod IV, resulting in similar clinical improvement in participants with gMG. Participants completing ADAPT-SC or enrolled in ADAPT+ (efgartigimod IV OLE) were eligible for the ongoing ADAPT-SC+ OLE.

Design/Methods:

Efgartigimod PH20 SC 1000 mg was administered in cycles of 4 once-weekly injections. Subsequent cycles were initiated ≥28 days from the last dose based on clinical evaluation. Myasthenia Gravis Activities of Daily Living (MG-ADL) score assessed clinical efficacy. 

Results:

As of December 2022, 179 participants received ≥1 dose of efgartigimod PH20 SC, with an average of ≈6 treatment cycles over a mean (SD) study duration of 413 (105) days, resulting in 193 patient-years of observation. Adverse events (AEs) were predominantly mild/moderate. Most frequent AEs were injection site erythema (29.1%), COVID-19 (22.3%), and headache (20.1%). Injection site reactions were mild/moderate, did not lead to treatment discontinuation, and decreased in incidence with subsequent cycles from 34.6% (n=62/179) in Cycle 1 to 11.5% (n=14/122) in Cycle 6. Improvement from cycle baseline (mean [SE] improvement at Week 4) was observed in Cycle 1 in MG-ADL total score (-4.1 [0.27]), Myasthenia Gravis Quality of Life 15-Item Questionnaire, Revised (MG-QoL15r) (-5.1 [0.44]), and EuroQoL 5-Dimension, 5-Level (EQ-5D-5L) (13.8 [1.54]), with consistent and repeatable improvements seen through Cycle 9. Observed improvements were similar to those seen with efgartigimod IV during ADAPT/ADAPT+.

Conclusions:

Treatment with multiple cycles of efgartigimod PH20 SC was well tolerated and efficacious, consistent with efgartigimod IV in ADAPT/ADAPT+.

10.1212/WNL.0000000000206401