Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study

Abstract

Background and purpose: Generalized myasthenia gravis (gMG) is a rare, chronic, neuromuscular autoimmune disease mediated by pathogenic immunoglobulin G (IgG) autoantibodies. Patients with gMG experience debilitating muscle weakness, resulting in impaired mobility, speech, swallowing, vision and respiratory function. Efgartigimod is a human IgG1 antibody Fc fragment engineered for increased binding affinity to neonatal Fc receptor. The neonatal Fc receptor blockade by efgartigimod competitively inhibits endogenous IgG binding, leading to decreased IgG recycling and increased degradation resulting in lower IgG concentration.

Methods: The safety and efficacy of efgartigimod were evaluated in the ADAPT study. Key efficacy outcome measures included Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Efgartigimod demonstrated significant improvement in both the MG-ADL and QMG scores. This post hoc analysis aimed to determine whether all subdomains of MG-ADL and QMG improved with efgartigimod treatment. Individual items of MG-ADL and QMG were grouped into four subdomains: bulbar, ocular, limb/gross motor and respiratory. Change from baseline over 10 weeks in each subdomain was calculated for each group.

Results: Greater improvements from baseline were seen across MG-ADL subdomains in participants treated with efgartigimod compared with placebo. These improvements were typically observed 1 to 2 weeks after the first infusion and correlated with reductions in IgG. Similar results were observed across most QMG subdomains.

Conclusions: These post hoc analyses of MG-ADL and QMG subdomain data from ADAPT suggest that efgartigimod is beneficial in improving muscle function and strength across all muscle groups, leading to the observed efficacy in participants with gMG.

Keywords: ADAPT; efgartigimod; generalized myasthenia gravis; immunoglobulin G; neonatal Fc receptor.

FIGURE 1

Percentage change from baseline in MG‐ADL subdomains over 10 weeks across cycles 1 and 2 in AChR‐Ab+ participants. Differences between treatment arms were noted across most MG‐ADL subdomains as early as 1–2 weeks after treatment. Each cycle consisted of 4 weekly infusions occurring at weeks 0, 1, 2 and 3 (yellow triangles) of either efgartigimod (10 mg/kg) or matching placebo. AChR‐Ab+, acetylcholine receptor antibody positive; MG‐ADL, Myasthenia Gravis Activities of Daily Living; SE, standard error. *p < 0.05 (two‐sample t test).

FIGURE 2

Percentage change from baseline in QMG subdomains over 10 weeks across cycles 1 and 2 in AChR‐Ab+ participants. As with MG‐ADL, differences between treatment arms were noted across most QMG subdomains as early as 1–2 weeks after treatment. Each cycle consisted of 4 weekly infusions occurring at weeks 0, 1, 2 and 3 (yellow triangles) of either efgartigimod (10 mg/kg) or matching placebo. AChR‐Ab+, acetylcholine receptor antibody positive; MG‐ADL, Myasthenia Gravis Activities of Daily Living; QMG, Quantitative Myasthenia Gravis; SE, standard error. *p < 0.05 (two‐sample t test).