In a new analysis of clinical trials assessing efgartigimod (Vyvgart; Argenx), the therapy was found to be well tolerated across indications and doses studied, with most treatment-related adverse events (TEAEs), including infections, being mild or moderate in severity and not dose-dependent.1 These findings suggest that efgartigimod is a safe therapy across different patient populations and different dosages in autoimmune diseases.
Efgartigimod demonstrated a consistent safety profile, with TEAE rates that were comparable with placebo and mild to moderate in severity. In the phase 3 ADAPT trial (NCT03669588), 77.4% of efgartigimod-treated patients reported TEAEs vs 84.3% in the placebo group. In the phase 3 ADVANCE trial (NCT04188379), 93.0% reported TEAEs when treated with efgartigimod vs 95.6% of those on placebo. Lastly, 85% efgartigimod-treated patients reported TEAEs in a phase 2 pemphigus trial (NCT03334058).
Clinical Takeaways
- Efgartigimod demonstrated a consistent safety profile and tolerability across various autoimmune diseases, making it a promising therapy for patients with IgG-mediated disorders.
- The therapy showed comparable rates of treatment-related adverse events with placebo in trials for myasthenia gravis, primary immune thrombocytopenia, and pemphigus, indicating its favorable tolerability.
- Efgartigimod's mechanism of action as an Fc fragment inhibitor offers a novel therapeutic approach for reducing pathogenic IgG autoantibodies in autoimmune disorders, making it a potential treatment option for these conditions.
These findings were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held November 1-4, in Phoenix, Arizona, by lead author Kelly Gwathmey, MD, associate professor of neurology, director of the ALS Clinic and chief of neuromuscular division at Virginia Commonwealth University, and colleagues. The safety of intravenous (IV) efgartigimod was assessed among patients with generalized myasthenia gravis (gMG) in the phase 2 and 3 ADAPT trials and a 3-year open-label extension ADAPT+ trial. The therapy was also assessed in patients with primary immune thrombocytopenia (ITP) in the ADVANCE trial, and in pemphigus (vulgaris and foliaceus) in an open-label trial. All of these studies investigated different dosing regimens of efgartigimod (10–25 mg/kg), including cyclical dosing in gMG and continuous weekly dosing in ITP and pemphigus.
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The discontinuation rates because of AEs were consistently low among the patients. In the ADAPT trial, 3.6% of patients in the efgartigimod group discontinued the treatment and 3.6% discontinued placebo. Among the patients in the ADVANCE trial, 3.5% discontinued when treated with efgartigimod with only 2.2% discontinued the placebo group. In total, 3% of participants from the pemphigus study discontinued efgartigimod. The therapy was well tolerated in ADAPT+, with no increase in TEAE incidence rates, which included infections, with repeated efgartigimod treatment for up to 19 cycles. The authors also noted that efgartigimod treatment did not reduce albumin levels or increase cholesterol levels.
Efgartigimod, a human IgG1 antibody Fc-fragment, blocks the neonatal Fc receptor and reduces IgG autoantibody levels. The treatment was originally approved in December 2021 based on significant findings from ADAPT. In the original analysis, the agent was shown to be well-tolerated and efficacious, meeting its primary end point of improvement in Myasthenia Gravis–Activities of Daily Living (MG-ADL) item scores relative with the placebo (67.7% vs 29.7%; P <.0001). Additionally, 40.0% of efgartigimod-treated patients who were anti-acetylcholine receptor (AChR) antibody positive achieved minimal or no symptoms compared with 11.1% treated with placebo.2
