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
Efgartigimod outperformed placebo on a number of secondary end points, including MG-ADL responders in the overall population, as well as both AChR-Ab+ and AChR– patients (P <.0001). It showed significant effects on time on trial in clinically meaningful improvement, defined as an MG-ADL improvement of 2 points or greater (P = .0001). Additionally, AChR-Ab+ patients, efgartigimod-treated patients showed significant differences compared with placebo in terms of fast onset of response on MG-ADL score, defined as onset observed in first 2 weeks (P = .0004). A sustained response was observed in 88.6% AChR-Ab+ patients who met the primary end point for at least 6 weeks, 56.8% for at least 8 weeks, and 34.1% for at least 12 weeks. Furthermore, 70.6% of AChR-Ab+ patients received a second treatment cycle, compared to only 25.6% of placebo patients.3
Of those in the treatment group 77% (n = 65) experienced TEAEs, while 84% (n = 70) of the placebo group did. The most frequent AEs reported were headache (efgartigimod: 29% [n = 24]; placebo: 28% [n = 23]) and nasopharyngitis (efgartigimod: 12% [n = 10]; placebo: 18% [n = 15]). Five percent (n = 4) of efgartigimod-treated patients and 8% (n = 7) patients in the placebo group had a serious TEAE, and each group had 3 patients (4%) discontinue treatment during the study.
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REFERENCES
1. Gwathmey K, Goebeler M, Broome CA, et al. Overview of the Safety Profile from Efgartigimod Clinical Trials in Participants With Diverse Immunoglobulin G-Mediated Autoimmune Diseases. Presented at: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting; November 1-4, 2023; Phoenix, AZ. Abstract 44.
2. FDA Approves New Treatment for Myasthenia Gravis. News release. FDA. December 17, 2021. Accessed Novemeber 2, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-myasthenia-gravis
3. Howard JF, Bril V, Vu T, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021;20(7):526-536. doi:10.1016/S1474-4422(21)00159-9
