Background: Nipocalimab is a fully-human, high-affinity, aglycosylated, effectorless monoclonal antibody designed to selectively block neonatal fragment-crystallizable receptor, thereby lowering IgG levels, including pathogenic autoantibodies. In the phase 3 Vivacity-MG3 study (NCT04951622), nipocalimab treatment demonstrated rapid, substantial and sustained lowering of total IgG.
Objectives: To evaluate the impact of nipocalimab on pre-existing clinically relevant anti-vaccine antibodies and humoral response to SARS-CoV-2 challenge in Vivacity-MG3 participants in the double-blind period. Participants received nipocalimab (30 mg/kg loading dose followed by 15 mg/kg afterwards) or placebo intravenously every 2 weeks for 24 weeks. Serum IgG antibody levels against tetanus toxoid (TT) and varicella zoster virus (VZV) were measured at baseline and post-treatment samples in a subset of participants. In participants with available samples and documented SARS-CoV-2 vaccination or infection during the study, antibodies against different epitopes of SARS-CoV-2 were measured.
Results: Nipocalimab reduced pre-existing anti-TT and anti-VZV antibodies similarly to total IgG (observed median pre-dose/minimal reduction at week 24: 69%). The majority of nipocalimab-treated participants who were immune to TT (n=18) and VZV (n=19) at baseline maintained protective antibody levels during the double-blind treatment period. One nipocalimab-treated participant received TT vaccination during treatment and exhibited increased and sustained anti-TT levels above the protective threshold post-vaccination. In nipocalimab-treated participants, SARS-CoV-2 vaccination (n=12) during treatment increased anti-spike antibodies, while SARS-CoV-2 infection (n=9) led to increased anti-spike and anti-nucleocapsid antibodies.
Conclusion: Nipocalimab-treated patients largely remained protected for TT and VZV and demonstrated preserved humoral responses to TT vaccination and SARS-CoV-2 infection/vaccination, supporting compatibility with recommended vaccination schedules.