B-Cell Therapy in IgAN: APRIL, BAFF, and the VISIONARY and ORIGIN Trials

This episode, "B-Cell Therapy in IgAN: APRIL, BAFF, and the VISIONARY and ORIGIN Trials," features the panel examining a class that changed the field.

Dr. Parikh introduces sibeprenlimab, an APRIL-neutralizing antibody approved in November 2025, and atacicept, a dual BAFF/APRIL antagonist approved in July 2026. He asks why the field succeeded with these targets after failing with anti-CD20. Dr. Rovin recalls that he and Dr. Fervenza published a negative anti-CD20 trial years ago. He explains the rationale for APRIL and BAFF rests on their role in B-cell class switching. Inhibiting APRIL prevents class switching into IgA, a likely mechanism of success. Dr. Rovin notes these agents hit the first three hits of the multi-hit hypothesis, the pathogenic immunologic core. Phase 2 and phase 3 data, he says, support IgA nephropathy as a B-cell-mediated disease. Dr. Parikh asks whether anti-CD20 failed because long-lived plasma cells lack CD20 expression. Dr. Rovin agrees this is plausible and says he would consider anti-CD19 over another anti-CD20, since CD19 reaches most plasma cells except the long-lived marrow-resident ones. He notes CD38 is also emerging as a target. Dr. Rovin reviews the VISIONARY data on sibeprenlimab. The nine-month approval data showed a proteinuria decline, and the GFR analysis at ERA showed placebo declining about six milliliters annualized versus three on drug. The absolute GFR change was flat in the sibeprenlimab group. He reports roughly 80% hematuria reduction and expected declines in IgA and galactose-deficient IgA1, with a good safety profile and monthly dosing. Dr. Parikh adds that the ORIGIN study of atacicept showed similar proteinuria reduction, with GFR data still pending. He notes the phase 2 atacicept study showed an 81% hematuria reduction, with sibeprenlimab around 70%.

Up next, in "Dual vs Single B-Cell Inhibition in IgAN: Duration and Safety Questions," the panel debates dual versus single B-cell inhibition and the open questions of treatment duration and long-term safety.