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

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.

• Authors: James F Howard Jr, Vera Bril, Ted M Burns, Renato Mantegazza, Malgorzata Bilinska, Andrzej Szczudlik, Said Beydoun, Francisco Javier Rodriguez De Rivera Garrido, Fredrik Piehl, Mariarosa Rottoli, Philip Van Damme, Tuan Vu, Amelia Evoli, Miriam Freimer, Tahseen Mozaffar, E Sally Ward, Torsten Dreier, Peter Ulrichts, Katrien Verschueren, Antonio Guglietta, Hans de Haard, Nicolas Leupin, Jan J G M Verschuuren, Efgartigimod MG Study Group
• Journal: Neurology (Neurology) Vol. 92 Issue 23 Pg. e2661-e2673 (06 04 2019) ISSN: 1526-632X [Electronic] United States
• PMID: 31118245 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 American Academy of Neurology.

Chemical References

• Adrenal Cortex Hormones
• Autoantibodies
• Cholinesterase Inhibitors
• Histocompatibility Antigens Class I
• Immunoglobulin Fc Fragments
• Immunologic Factors
• Immunosuppressive Agents
• Receptors, Cholinergic
• Receptors, Fc
• Fc receptor, neonatal

Topics

• Activities of Daily Living
• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Aged
• Autoantibodies (immunology)
• Cholinesterase Inhibitors (therapeutic use)
• Double-Blind Method
• Female
• Histocompatibility Antigens Class I
• Humans
• Immunoglobulin Fc Fragments (therapeutic use)
• Immunologic Factors (therapeutic use)
• Immunosuppressive Agents (therapeutic use)
• Male
• Middle Aged
• Myasthenia Gravis (drug therapy, immunology)
• Receptors, Cholinergic (immunology)
• Receptors, Fc (antagonists & inhibitors)
• Treatment Outcome
• Young Adult