Overview of the Safety Profile from Efgartigimod Clinical Trials in Participants with Diverse IgG-mediated Autoimmune Diseases
Tuan Vu1, Kelly Gwathmey2, Catherine Broome3, Matthias Goebeler4, Hiroyuki Murai5, Zsuzsanna Bata-Csörgo6, Adrian Newland7, Peter Ulrichts8, Rene Kerstens8, Jeffrey T. Guptill8, Sofiane Agha8, Ming Jiang8, James Howard9
1Department of Neurology, University of South Florida, 2Department of Neurology, Virginia Commonwealth University, 3Department of Medicine, Georgetown University, 4Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, 5Department of Neurology, International University of Health and Welfare, 6Department of Dermatology and Allergology, University of Szeged, 7Centre for Haematology, Barts and the London School of Medicine and Dentistry, 8argenx, 9Department of Neurology, The University of North Carolina, Dept of Neurology, CB 7025
Objective:

To assess the safety profile of efgartigimod across different IgG-mediated disorders.

Background:

Efgartigimod is a first-in-class, human IgG Fc fragment that inhibits the neonatal Fc receptor (FcRn) and outcompetes endogenous IgG binding. This results in reduced recycling and increased degradation of IgGs, including pathogenic IgG autoantibodies. FcRn inhibition by efgartigimod is a rational therapeutic option for IgG-mediated autoimmune disorders.

Design/Methods:

Intravenous (IV) efgartigimod safety was assessed in generalized myasthenia gravis (gMG) in phase 2, phase 3 (ADAPT) trials, and a 3-year open-label extension (ADAPT+) trial. It was also evaluated in primary immune thrombocytopenia (ITP) in a phase 3 trial (ADVANCE) and a 4-year open-label extension (ADVANCE+) as well as in an open-label phase 2 trial in pemphigus (vulgaris and foliaceus). These studies examined different dosing regimens (10-25 mg/kg) of efgartigimod, including cyclical dosing in gMG and continuous weekly dosing in ITP and pemphigus.

Results:

Across all indications and doses studied, efgartigimod demonstrated a consistent safety profile, with comparable treatment emergent adverse event (TEAE) rates to placebo (ADAPT 77.4% efgartigimod/84.3% placebo; ADVANCE 93.0% efgartigimod/95.6% placebo; 85% of participants in the open label pemphigus study). Most TEAEs across studies were mild to moderate in severity. Discontinuation rates due to adverse events were consistently low across studies (3.6% efgartigimod group/3.6% placebo in ADAPT; 3.5% efgartigimod/2.2% placebo in ADVANCE; and 3% of pemphigus study participants). Efgartigimod was well tolerated in ADAPT+ and ADVANCE+, with no increase in TEAE incidence rates or infections with repeated treatment. Efgartigimod treatment did not reduce albumin levels or increase cholesterol levels.

Conclusions:

Efgartigimod is well tolerated across indications and doses studied. Most TEAEs, including infections, were mild or moderate in severity and did not increase in frequency with recurrent dosing.

10.1212/WNL.0000000000206331