Overview of the Safety Profile from Efgartigimod Clinical Trials in Participants with Diverse IgG-Mediated Autoimmune Diseases (P1-5.001)

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. Disclosure: Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Strongbridge. Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Gwathmey has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. Dr. Gwathmey has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals. Dr. Broome has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Broome has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Broome has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Broome has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Incyte. The institution of Dr. Broome has received research support from Argenx. The institution of Dr. Broome has received research support from Sanofi. The institution of Dr. Broome has received research support from Incyte. The institution of Dr. Broome has received research support from Rigel. Prof. Goebeler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Almirall. The institution of Prof. Goebeler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Prof. Goebeler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GSK. Prof. Goebeler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GSK. Prof. Goebeler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Prof. Goebeler has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lilly. The institution of Prof. Goebeler has received research support from Argenx. Prof. Goebeler has received personal compensation in the range of $0-$499 for serving as a travel expenses with UCB. Dr. Murai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Murai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Murai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Murai has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Chugai Pharmaceutical. The institution of Dr. Murai has received research support from Japan Blood Products Organization. Prof. Bata-Csorgo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme Hungary. The institution of Prof. Bata-Csorgo has received research support from NKFI Hungary. Prof. Bata-Csorgo has received publishing royalties from a publication relating to health care. Prof. Newland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for OakHill Bio. Prof. Newland has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Prof. Newland has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Angle PLC. Prof. Newland has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Taylor and Francis. Prof. Newland has received personal compensation in the range of $10,000-$49,999 for serving as a Chair, Clinical Board with BMI Healthcare. Peter Ulrichts has received personal compensation for serving as an employee of argenx. Peter Ulrichts has stock in argenx. Mr. Kerstens has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Argenx. Dr. Guptill has received personal compensation for serving as an employee of argenx. Dr. Guptill has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Guptill has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Guptill has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Toleranzia. Dr. Guptill has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Guptill has stock in argenx. The institution of Dr. Guptill has received research support from NIH. The institution of Dr. Guptill has received research support from MGFA. The institution of Dr. Guptill has received research support from PCORI. The institution of Dr. Guptill has received research support from Verily. The institution of Dr. Guptill has received research support from UNC. Dr. Guptill has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Agha has received personal compensation for serving as an employee of argenx. Mrs. Jiang has received personal compensation for serving as an employee of argenx BV. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for arenx BVBA. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Regeneron Pharmaceuticals. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunivant. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ra Pharma (now UCB Biosciences). Dr. Howard has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio (Horizon Therapeutics). Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi US. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Academic CME. Dr. Howard has stock in General Electric dividends. Dr. Howard has stock in Johnson & Johnson dividends. Dr. Howard has stock in Pfizer dividends. An immediate family member of Dr. Howard has stock in GlaxoSmithKline dividends. The institution of Dr. Howard has received research support from Alexion Pharmaceuticals. The institution of Dr. Howard has received research support from argenx BVBA. The institution of Dr. Howard has received research support from Ra Pharma (now UCB Biosciences). The institution of Dr. Howard has received research support from NIH. The institution of Dr. Howard has received research support from Centers for Disease Control/Research Triangle Institute. The institution of Dr. Howard has received research support from Duke University (DCRI). The institution of Dr. Howard has received research support from Millenium Pharmaceuticals. The institution of Dr. Howard has received research support from Cartestian Therapeutics. Dr. Howard has a non-compensated relationship as a Scientific Advisiory Board member, Committee member with Myasthenia Gravis Foundation of America that is relevant to AAN interests or activities. Dr. Howard has a non-compensated relationship as a Committee member with American Assoc Neuromuscular and Electrodiagnostic Medicine that is relevant to AAN interests or activities.