VIVACITY-MG: a PHASE 2, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, EFFICACY, PHARMACOKINETICS, PHARMACODYNAMICS, AND IMMUNOGENICITY OF NIPOCALIMAB ADMINISTERED TO ADULTS WITH GENERALIZED MYASTHENIA GRAVIS

Background. The objective of this study is to evaluate the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of nipocalimab vs. placebo in patients with generalized myasthenia gravis (gMG) who have had an insufficient response to ongoing, standard‐of‐care therapy. Nipocalimab (M281) is a fully human, aglycosylated, effectorless IgG1 anti‐FcRn monoclonal antibody that targets the IgG binding site on FcRn with high affinity, thereby interfering with the binding of IgG. IgG that is not bound to FcRn cannot be recycled and thus undergoes lysosomal degradation. This is expected to reduce serum levels of total IgG and pathogenic IgG autoantibodies that cause MG and ameliorate the disease. Methods. 68 patients were randomized 1:1:1:1:1 to 4 treatment groups or a placebo group. To maintain study blinding, all patients received an intravenous infusion (either nipocalimab or placebo) every other week for a total of 5 infusions during the 8‐week treatment period. After completion of the follow‐up period, patients could enroll in a separate open‐label extension study and receive treatment with nipocalimab. Results. There were no discontinuations due to treatment‐emergent adverse events (AEs), severe AEs, or related serious AEs with nipocalimab. The incidence of infections and headaches with nipocalimab were comparable to placebo. Nipocalimab was well‐tolerated and achieved substantial, dose‐dependent and rapid reductions in serum total IgG, including all IgG subtypes and anti‐AChR autoantibodies. Treatment with nipocalimab resulted in a robust and significantly greater mean improvement from baseline in MG activities of daily living (MG‐ADL) scores across all continuous dosing arms vs. placebo at the end of the treatment period. A greater proportion of patients treated with nipocalimab exhibited rapid improvement (within two weeks of treatment) in MG‐ADL across all 4 dosing arms vs. placebo. 51.9% of patients who received nipocalimab (all doses) reported a durable MG‐ADL response vs. 15.4% of those who received placebo (p=0.017). Conclusions. Nipocalimab was well‐tolerated, safe, and efficacious in patients with gMG.