Efgartigimod newly gains FDA approval for Treating generalized MG

25 Feb 2022

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

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