Recently, the United States (US) Food and Drug Administration (FDA) has approved a novel treatment for generalized myasthenia gravis (MG).¹ Efgartigimod is the first of a new class of medication for this rare autoimmune neuromuscular disease.¹ Recent finding published in the Lancet Neurology suggested that the safety, efficacy and tolerability of efgartigimod were more favorable in treating generalized MG patients than the existing therapies.²

Generalized MG is a rare chronic autoimmune disorder that can occur at any age.³ It is characterized by debilitating weakened skeletal muscles which may result in impaired respiratory, speech, motility function, trouble swallowing, and drooping eyelids.^1,3 Autoreactive immunoglobulin G (IgG) plays a pivotal role in generalized MG pathology.5 The neonatal Fc receptor (FcRn) binds IgG autoantibodies and extends its half-life and recycles it back into circulation.⁴ In other words, FcRn sustains the availability of pathogenic IgG antibodies in autoantibody-mediated generalized MG.^2,4 Therefore, inhibiting the abundant IgG autoantibodies from binding to the FcRn would be a beneficial targeted treatment for generalized MG.⁴

Efgartigimod (ARGX-113) is an engineered human-derived Fc antibody fragment which possesses a high affinity for the FcRn.^1,2,5 Howard et al. conducted a multicenter, randomized, placebo-controlled, phase 3 trial (ADAPT) trial to evaluate the safety, tolerability and efficacy of efgartigimod in generalized MG patients.² In this study, participants (n=167; 84 in the efgartigimod group; 83 in the placebo group) were recruited from 56 academic and community centers over 15 countries across North America, Europe, and Japan, and the study lasted for a period of 26 weeks in 2018-2019.² Of the total number of participants, 129 (77%) were acetylcholine receptor antibody-positive and 38 (23%) were acetylcholine receptor antibody-negative.² Patients were at least 18 years of age, with or without acetylcholine receptor antibodies, and had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5, and were on a stable dose of at least 1 treatment for generalized GM before and throughout the study.² Patients were given 10mg/kg of efgartigimod in the test group and matching placebo in the control group as 4 infusions per cycle (1 infusion per week) with at least 5 weeks of follow-up after each cycle.²

Efficacy was assessed with the MG-ADL scale, Quantitative Myasthenia Gravis (QMG) score, Myasthenia Gravis Composite (MGC) scale, 15-item revised version of the Myasthenia Gravis Quality of Life (MG-QoL15r) questionnaire, and EQ5D quality of life scale.² These assessments were performed weekly for 8 weeks after the start of each cycle, then every 2 weeks up to 26 weeks.²

The primary endpoint for efficacy was the proportion of acetylcholine receptor antibody-positive patients who were the MG-ADL responders in the initial treatment cycle.² The MG-ADL responders were those who achieved at least a 2-point reduction in score, lasting for at least 4 consecutive weeks.² Results showed that treatment with efgartigimod had a significant improvement on the MG-ADL scale compared with no treatment (68% vs. 30%; p<0.0001).² The treatment group also demonstrated greater total mean score improvements in the QMG, MGC and MG-QoL15r in cycle 1 vs. the placebo group.²

Safety was assessed by alterations in clinical laboratory values, vital signs, echocardiograms, as well as the development of adverse events (AEs).² About 77% of the efgartigimod-treated group showed AEs in contrast to 84% of the placebo group.² The observed AEs included headaches, nasopharyngitis, nausea, diarrhea, upper respiratory tract infections, and urinary tract infections.² There were no significant changes in hematology or chemistry parameters, electrocardiogram, or vital signs in either group.² No deaths occurred during the trial.²  

The current therapies adopted for generalized MG are corticosteroids, anticholinesterase medications and immunosuppressants. Yet, they may have undesirable side effects and are at high costs.⁵ Efgartigimod provides an alternative treatment by ways of reducing pathogenic IgG autoantibodies and blocking the FcRn receptor.⁵ The ADAPT trial demonstrated that efgartigimod could be a novel, efficacious and well-tolerated treatment for generalized MG patients.²