Overview of the Safety Profile From Efgartigimod Clinical Trials in Participants With Diverse IgG-Mediated Autoimmune Diseases

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Michelle Sholzberg
Kelly Gwathmey
Catherine M. Broome
Matthias Goebeler
Hiroyuki Murai
Zsuzsanna Bata-Csörgo
Adrian Newland
Peter Ulrichts
Rene Kerstens
Jeffrey T. Guptill
Sofiane Agha
Ming Jiang
James F. Howard Jr


Efgartigimod, FcRn, Pemphigus, Myasthenia Gravis, Generalized Myasthenia Gravis, Primary Immune Thrombocytopenia



Efgartigimod is a first-in-class, human immunoglobulin-G (IgG) Fc fragment that inhibits the neonatal Fc receptor (FcRn) and outcompetes endogenous IgG binding. FcRn inhibition by efgartigimod is a rational therapeutic option for IgG-mediated autoimmune disorders, including immune thrombocytopenia (ITP).


To determine the safety profile of efgartigimod for a variety of IgG-mediated autoimmune disorders, including ITP.


Intravenous efgartigimod safety was assessed in a phase 3 (ADVANCE) trial in ITP. It was also evaluated in generalized myasthenia gravis (gMG) in phase 2 and 3 (ADAPT) trials and a 3-year open-label extension (ADAPT+) along with an open-label phase 2 trial in pemphigus. Varying dosing regimens of efgartigimod (10-25 mg/kg) were used, including cyclical (gMG) and continuous weekly dosing (ITP, pemphigus).


Across all indications and doses studied, efgartigimod demonstrated a consistent safety profile, with comparable treatment emergent adverse event (TEAE) rates to placebo (ADVANCE 93.0% efgartigimod vs. 95.6% placebo; ADAPT 77.4% efgartigimod vs. 84.3% placebo; 85% of participants in open label pemphigus study). Most TEAEs across studies were mild to moderate in severity. Discontinuation rates due to adverse events were low across studies (3.5% efgartigimod vs. 2.2% placebo in ADVANCE; 3.6% efgartigimod vs. 3.6% placebo in ADAPT; 3% in pemphigus). No increase in TEAE incidence rates or infections with repeated efgartigimod cycles (up to 19) in ADAPT+ was observed. In ADVANCE, no thromboembolic TEAEs were reported. Efgartigimod did not impair participant ability to generate new specific IgG responses to non-live vaccines, regardless of the timing of vaccinations however, there were transient reductions in specific IgG titers observed.


Efgartigimod was generally 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. Non-live vaccine responsiveness was preserved. There were no thromboembolic events in those treated for ITP.


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