Clinical & Regimen Controls
Regimen Active
Endosomal FcRn Blockade Flux
Blockade: 88%
■ Efgartigimod (Fc-fragment) out-competes endogenous ● Pathogenic IgG for FcRn binding at pH 6.0, shunting free IgG into lysosomal catabolism.
Total IgG Clearance & Clinical Total Improvement Score (TIS)
Total IgG
Pathogenic Autoantibody
TIS Score
Peak IgG Reduction
64.2%
Nadir: 4.4 g/L
Autoantibody Half-Life (t½)
3.8 days
Normal IgG t½: 21.0 d
Degradation Flux Increase
3.2x
Target Occupancy: 88%
Predicted TIS (Week 8)
42.6
Moderate Improvement (≥40)
Comparative Mechanism Benchmark (Myositis)
| Modality | Target Mechanism | Onset Speed | IgG Depletion | Infection Risk |
|---|---|---|---|---|
| Efgartigimod (FcRn) | Selective IgG recycling blockade | Rapid (1–2 wks) | ~65% selective | Low (IgA/M spared) |
| IVIg (High Dose) | FcRn saturation + scavenging | Moderate (2–4 wks) | Indirect (~30%) | Moderate (Volume load) |
| Rituximab (Anti-CD20) | B-cell lineage depletion | Delayed (8–16 wks) | De novo synthesis | Elevated (Prolonged) |
| Pulsed Steroids | Broad NF-κB transcription block | Rapid (Days) | Non-specific | High (Metabolic/Infect.) |
Clinical Trial Dossier & Kinetic Summary
Source Context: Grounded in Argenx's Phase 2/3 idiopathic inflammatory myopathy trial readouts across Dermatomyositis (DM), Polymyositis (PM), and Necrotizing Myopathy (IMNM).
Pathophysiological Note: Accelerating IgG catabolism by clearing the neonatal Fc receptor reduces pathogenic autoantibodies (anti-Mi-2, anti-Jo-1, anti-SRP) without triggering generalized immunosuppression.