Abstract Details

Nipocalimab is a fully human, aglycosylated, effectorless IgG1 anti-FcRn monoclonal antibody that targets the neonatal Fc receptor (FcRn) with high affinity, resulting in lowering of total IgG and IgG pathogenic antibodies in autoimmune disease. In the Vivacity Phase 2 study, nipocalimab was evaluated in generalized myasthenia gravis (gMG) patients with inadequate disease control.   

To evaluate the relationship between clinical improvement in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores and the pharmacodynamic effects of IgG and autoantibody lowering induced by nipocalimab in the Vivacity Phase 2 gMG study.

The relationship between both the reduction in total IgG and in acetylcholine-receptor (AChR)- and Muscle-Specific-Tyrosine-Kinase (MuSK)- autoantibodies with improvement in MG-ADL scores were explored across the four nipocalimab dosing arms in the Vivacity Phase 2 gMG Study. 

Of the 68 patients enrolled, 54 were randomized to one of the four nipocalimab dosing arms. 51 (94%) were seropositive for anti-AChR, 3 (6%) for anti-MuSK. Nipocalimab was well-tolerated and achieved substantial, dose-dependent and rapid reductions in serum total IgG, including all IgG subtypes and anti-AChR autoantibodies. These reductions were associated with dose-dependent, durable and rapid MG-ADL responses in all nipocalimab-treated groups. Though the sample of anti-MuSK-positive patients was small, a similar trend in IgG reduction was noted in those patients. 

The results of this analysis support both the centrality of anti-neuromuscular junction protein IgG autoantibodies in the pathogenesis of gMG as well as the rapid, dose-dependent and predictable effect of nipocalimab in lowering these pathogenic autoantibodies and induction of clinical improvement in patients with gMG.  In addition, the close correlation between serum IgG, anti-AChR and clinical response suggest the potential of using serial serum IgG levels as a biomarker of drug effect in management of gMG patients treated with nipocalimab; this will be further tested in the ongoing Vivacity Phase 3 gMG trial.