Efgartigimod: A Comprehensive Clinical and Pharmacological Monograph

Section 1: Introduction to Efgartigimod and the Neonatal Fc Receptor (FcRn) Pathway

1.1 The Pathogenic Role of Immunoglobulin G (IgG) in Autoimmune Disease

A vast and heterogeneous group of debilitating conditions, collectively known as autoimmune diseases, are characterized by an aberrant immune response directed against self-antigens. In a significant subset of these disorders, the primary drivers of pathology are autoantibodies of the immunoglobulin G (IgG) isotype.[1] These pathogenic IgGs erroneously target and bind to critical proteins, receptors, or cellular components, disrupting normal physiological processes and leading to inflammation, tissue damage, and organ dysfunction. For instance, in generalized myasthenia gravis (gMG), autoantibodies attack components of the neuromuscular junction, most commonly the acetylcholine receptor (AChR), which impairs neuromuscular transmission and results in profound muscle weakness.[2] Similarly, in chronic inflammatory demyelinating polyneuropathy (CIDP), there is increasing evidence that IgG autoantibodies target proteins on peripheral nerves, leading to demyelination, progressive weakness, and sensory loss.[4]

The therapeutic challenge in managing these conditions has historically been the difficulty of selectively neutralizing or removing these pathogenic IgG molecules without inducing broad, non-specific immunosuppression. Traditional therapies often involve corticosteroids or other immunosuppressants that carry a substantial burden of side effects and may not be sufficiently effective for all patients.[3] This has created a significant unmet medical need for targeted therapies that can precisely address the underlying autoimmune mechanism with a more favorable safety profile.[1]

1.2 The Neonatal Fc Receptor (FcRn): A Master Regulator of IgG Homeostasis