Efgartigimod in myasthenia gravis: Phase 3 trial design

Introduction: Myasthenia gravis (MG), an autoimmune disease causing debilitating muscle weakness, is mediated by IgG autoantibodies. Neonatal Fc receptor (FcRn) recycles IgG extending its half-life. Efgartigimod, a human IgG1 antibody Fc-fragment engineered for optimal blocking of FcRn, outcompetes endogenous IgG-binding, prevents IgG recycling, reducing IgG and autoantibody levels. Methods: This 26-week, randomised double-blind, placebo-controlled Phase 3 trial of efgartigimod evaluates efficacy, safety, and quality of life in patients (age >18 years) diagnosed with generalized MG class II, III, and IV on stable concomitant standard of care MG therapy. Inclusion criteria are MG-ADL score of ≥5 points (>50% non-ocular). A maximum of 20% of acetylcholine receptor antibody (AChR-Ab) seronegative patients will be allowed in the trial. Following screening, eligible patients receive 4 weekly doses of IV 10mg/kg. Subsequent treatment is tailored according to clinical condition, based on MG-ADL score. Results: 167 patients enrolled at 51 sites in 15 countries. Efficacy endpoint is the percentage of AChR-Ab seropositive patients whose MG-ADL decreases within the first treatment cycle by at least 2 points from baseline for ≥4 consecutive weeks. 2ndary endpoints include additional MG-ADL and QMG assessments. Conclusion: Efficacy and safety findings will be reported at the conclusion of the trial.