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

Authors

James F. Howard, University of North Florida
Vera Bril, University of North Florida
Ted M. Burns, University of North Florida
Renato Mantegazza, University of North Florida
Malgorzata Bilinska, University of North Florida
Andrzej Szczudlik, University of North Florida
Said Beydoun, University of North Florida
Francisco Javier Rodriguez De Rivera Garrido, University of North Florida
Fredrik Piehl, University of North Florida
Mariarosa Rottoli, University of North Florida
Philip Van Damme, University of North Florida
Tuan Vu, University of North Florida
Amelia Evoli, University of North Florida
Miriam Freimer, University of North Florida
Tahseen Mozaffar, University of North Florida
E. Sally Ward, University of North Florida
Torsten Dreier, University of North Florida
Peter Ulrichts, University of North Florida
Katrien Verschueren, University of North Florida
Antonio Guglietta, University of North Florida

Document Type

Article

Publication Date

6-4-2019

Abstract

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. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.

Publication Title

Neurology

Volume

92

Issue

23

First Page

e2661

Last Page

e2673

Digital Object Identifier (DOI)

10.1212/WNL.0000000000007600

PubMed ID

31118245

E-ISSN

1526632X

Citation Information

Howard, J.F., Bril, V., Burns, T.M., Mantegazza, R., Bilinska, M., Szczudlik, A., Beydoun, S., De Rivera Garrido, F. J. R., Piehl, F., Rottoli, M., Van Damme, P., Vu, T., Evoli, A., Freimer, M., Mozaffar, T., Ward, E.S., Dreier, T., Ulrichts, P., Verschueren, K., Guglietta, A. (2019) Randomized Phase 2 Study of FcRn Antagonist Efgartigimod in Generalized Myasthenia Gravis. Neurology, 92(23), e2661-e2673.