Efgartigimod: A First-in-class Investigational Antibody Fragment for the Treatment of Generalized Myasthenia Gravis

Myasthenia gravis (MG) is a rare autoimmune disorder characterized by fatigue and muscle weakness. About 85–90% of patients with generalized MG display pathogenic immunoglobulin (Ig)G antibodies against the skeletal muscle nicotinic acetylcholine receptor (AChR), the muscle-specific tyrosine kinase or the lipoprotein receptor-related protein, which all exert their effect by disrupting neuromuscular transmission. Therapy for MG includes immunomodulation and non-specific immunosuppression; the latter comprises corticosteroids and non-steroidal immunosuppressive therapies, which non-selectively suppress the immune system and are frequently accompanied by burdensome side effects. This, together with the fact that up to 20% of patients are refractory to immunosuppressive therapy, highlights a compelling unmet need for more effective and better-tolerated therapies. Efgartigimod, a humanized IgG1-derived fragment crystallizable region that competitively blocks the neonatal fragment crystallizable receptor, holds great promise in meeting this need, having good tolerability and a more targeted effect. Efgartigimod has been recently approved by the US Food and Drug Administration (FDA) for the treatment of AChR-positive patients with generalized MG, making it the first FDA-approved neonatal fragment crystallizable receptor antagonist. This review focuses on the clinical development of efgartigimod, which offers an encouraging new therapeutic option for generalized MG.