2023 American Academy of Neurology Abstract Website

Kelly Gwathmey¹, Catherine Broome², Matthias Goebeler³, Hiroyuki Murai⁴, Zsuzsanna Bata-Csorgo⁵, Adrian Newland⁶, Peter Ulrichts⁷, Rene Kerstens⁷, Jeffrey Guptill⁷, Sofiane Agha⁷, Ming Jiang⁷, James Howard⁸
¹Department of Neurology, Virginia Commonwealth University, ²Department of Medicine, Georgetown University, ³Department of Dermatology, Venereology and Allergology, University Hospital Wϋrzburg, ⁴Department of Neurology, School of Medicine, International University of Health and Welfare, ⁵Department of Dermatology and Allergology, University of Szeged, ⁶Centre for Haematology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, ⁷argenx, ⁸Department of Neurology, The University of North Carolina at Chapel Hill

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 a phase 3 trial (ADVANCE) in primary immune thrombocytopenia (ITP) and 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+, with no increase in TEAE incidence rates or infections with repeated efgartigimod cycles (up to 19). 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.