WCN26-1872 PRESERVATION OF HUMORAL IMMUNITY AND RESPONSE TO VACCINATION AND INFECTION IN FELZARTAMAB-TREATED PATIENTS WITH IgA NEPHROPATHY: DATA FROM THE PHASE 2 IGNAZ STUDY

Introduction: Depletion of B lineage cells, including plasma cells, is a promising therapeutic strategy for immune-mediated diseases but can potentially reduce humoral immunity.Felzartamab, a fully human anti-CD38 monoclonal antibody targeting CD38+ plasmablasts and plasma cells, is under investigation in multiple immune-mediated diseases including immunoglobulin A nephropathy (IgAN) and primary membranous nephropathy (PMN).Results in PMN demonstrated preservation of vaccine immunity among felzartamab-treated patients.This analysis examined humoral responses in felzartamab-treated patients with IgAN.Methods: In the Phase 2 IGNAZ study (NCT05065970), 48 patients with IgAN were randomized 1:1:1:1 in Part 1 to placebo or intravenous felzartamab (2 doses in 15 days, 5 doses in 2 months, or 9 doses in 5 months).In Part 2, 6 Japanese patients received the open-label 9-dose regimen.Serum samples were collected during on-and off-treatment periods and assessed using the Elecsys Anti-SARS-CoV-2 S Assay (Roche Diagnostics) and VaccZyme Anti-Tetanus Toxoid (TT) IgG Enzyme Immunoassay (MK010).Results: Of 54 patients enrolled, 46/53 with available data had protective anti-TT titers at baseline and 45/48 had positive anti-SARS-CoV-2 titers.Baseline anti-TT immunity was maintained throughout the study; 4 patients (1 placebo) decreased to below protective titer (<0.1 U/mL) during the study; however, all had low baseline titers and reductions were minimal with titers staying >0.08 U/mL.Similarly, patients maintained positive baseline titers of anti-SARS-CoV-2 during the study.Across arms, 16 patients received $1 SARS-CoV-2 vaccination on study and 17 patients experienced acute SARS-CoV-2 infections.Seven of 8 patients with data pre-and post-vaccination mounted a vaccine response regardless of treatment arm.Similarly, 5/6 patients generated antibody responses to SARS-CoV-2 infection while receiving treatment.Conclusion: Patients with IgAN receiving felzartamab demonstrated preservation of humoral immunity, which may contribute to a favorable safety profile versus other B-cell targeting therapies.These findings are consistent with those previously observed in PMN.