Data from: Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis

Objective: To 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. Methods: A 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. Results: Of 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. Conclusions:
Efgartigimod 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.