Abstract-Text (inkl. Referenzen)

Introduction IgG autoantibodies are key in autoimmune disease pathogenesis and neurological conditions.

Methods Efgartigimod (EFG), an FcRn antagonist, is a human IgG1-derived Fc-fragment that reduces recycling and increases IgG degradation, including all IgG subtypes, without impacting other immunoglobulins or albumin.

Results Based on the ADAPT study, EFG is approved for treatment of adult patients with AChR-Ab+ generalized myasthenia gravis in several countries. Ongoing studies: phase 3 study in immune thrombocytopenia (ITP; ADVANCE SC), pemphigus vulgaris and foliaceus (ADDRESS), and phase 2/3 studies in chronic inflammatory demyelinating polyneuropathy (ADHERE), bullous pemphigoid (BALLAD), and myositis (ALKIVIA). ADVANCE primary endpoint met with higher, sustained platelet response with IV EFG vs placebo in ITP. Across all completed studies to date, EFG reduced total IgG, including pathogenic IgG, corresponding to clinical improvements in each population. EFG safety is consistent, with comparable treatment emergent adverse event (TEAE) rates to placebo (ADAPT 77.4% EFG/84.3% placebo; ADVANCE 93.0% EFG/95.6% placebo; 85% patients open-label pemphigus study). Most TEAEs were mild to moderate in severity. EFG was well tolerated in ADAPT+ extension study, with no increase in TEAE rates or infections with up to 19 treatment cycles.

Summary FcRn inhibition by EFG is a promising therapeutic option for autoimmune diseases mediated by pathogenic IgG autoantibodies.