Report on additional analyses from a randomized, double-blind phase 2 study of efgartigimod in generalized Myasthenia Gravis (gMG)

gMG is mediated by pathogenic IgG autoantibodies causing acetylcholine receptor (AChR) blockade, accelerated receptor degradation and complement activation.

The neonatal Fc receptor (FcRn) recycles IgG, rescues it from degradation, and is therefore responsible for the long half-life of IgGs.  Blocking FcRn function to reduce IgG autoantibody levels is a logical potential therapeutic approach for MG.

Efgartigimod is a human IgG1 antibody Fc-fragment, a natural ligand of FcRn, engineered for increased, pH-dependent, FcRn affinity. Efgartigimod outcompetes endogenous IgG binding, preventing recycling, increasing IgG degradation.

24 patients with gMG, MG-ADL ≥ 5, were randomized to receive 4 weekly IV infusions of 10mg/kg efgartigimod, or placebo, plus their established MG therapy. The primary endpoint was safety; secondary endpoints included change in MG-ADL, QMG, and pharmacodynamics.

Efgartigimod resulted in targeted reduction of all IgG subtypes, reduced AChR-antibodies, without impacting levels of other immunoglobulin isotypes or albumin.

Clinically meaningful and sustained improvements in symptoms across four MG scales were seen with efgartigimod. 75% of efgartigimod patients achieved ≥2-point reduction in MG-ADL for ≥6 consecutive weeks versus 25% for placebo (p=0.039).

Further analyses found 6/12 efgartigimod patients maintained clinically meaningful improvement of MG-ADL score 8 weeks after last dose (end of study), suggesting sustained effect beyond IgG reduction. Minimum Symptom Expression (MG-ADL 0 or 1) at any time during study was achieved by 5/12 (42%) efgartigimod and 1/12 (8%) placebo.

No safety concerns identified.   Additional pharmacodynamic, safety and efficacy data will be presented.

Efgartigimod reduced IgG and AChR-antibodies, and improvement in gMG symptoms was sustained to end of study with no safety concerns identified. It may be an innovative approach to gMG management.  A global phase 3 study is ongoing.