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argenx BVBA.

ObjectiveTo investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment.MethodsA phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity.ResultsOf the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement.ConclusionsEfgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG.Classification of evidenceThis study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.

ObjectiveTo evaluate the safety and efficacy of efgartigimod in patients with generalized myasthenia gravis (MG) enrolled in the ADAPT+ long-term extension study.BackgroundTreatment with efgartigimod, a human IgG1 antibody Fc-fragment that blocks neonatal Fc receptor, resulted in clinically meaningful improvement (CMI) in MG-specific outcome measures in the ADAPT phase 3 clinical trial. All patients who completed ADAPT were eligible to enroll in its ongoing open-label, 3-year extension study, ADAPT+.Design/MethodsEfgartigimod (10 mg/kg IV) was administered in cycles of once-weekly infusions for 4 weeks, with subsequent cycles initiated based on clinical evaluation. Efficacy was assessed during each cycle utilizing Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scales.ResultsNinety-one percent of ADAPT patients (151/167) entered ADAPT+. As of February 2021, 106 AChR-Ab+ and 33 AChR-Ab– patients had received at least 1 dose of open-label efgartigimod (including 66 ADAPT placebo [PBO] patients). The mean (SD) study duration was 363 (114) days, resulting in 138 patient-years of observation. Similar incidence rates per patient year (IR/PY) of serious adverse events were seen in ADAPT (efgartigimod: 0.11; placebo: 0.29) compared to ADAPT+ (0.25). Five deaths (acute myocardial infarction, COVID-19 pneumonia/septic shock, bacterial pneumonia/MG crisis, malignant lung neoplasm, and unknown [multiple cardiovascular risk factors identified on autopsy]) occurred; none were considered related to efgartigimod by the investigator. AEs were predominantly mild or moderate. CMI was observed in AChR-Ab+ patients during each cycle (up to 10 cycles) at magnitudes comparable to improvements observed at week 3 of cycle 1 (mean[SE] improvements: MG-ADL, –5.1[0.34]; QMG, –4.7[0.41]). Clinical improvements mirrored maximal reductions in total IgG and AChR-Abs across all cycles.ConclusionsThis analysis suggests the efficacy of long-term treatment with efgartigimod was consistent across multiple cycles. No new safety signals were identified, despite being conducted before vaccine availability during the COVID-19 pandemic.

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