Additional Emerging BAFF and APRIL Inhibitors in IgAN

In this segment, the panel reviews the emerging clinical data for two additional BAFF/APRIL–pathway inhibitors: sibeprenlimab and povetacicept. They first discuss sibeprenlimab, noting that phase 2 data demonstrated dose-dependent reductions in proteinuria along with sustained suppression of serum galactose-deficient IgA1 levels, supporting the mechanism of targeting upstream production of pathogenic IgA. The panel highlights that these effects were observed without broad immunosuppression, which may offer a favorable safety profile compared with systemic corticosteroids. The discussion then moves to povetacicept, which also targets BAFF and APRIL but with a slightly different binding and receptor engagement profile. Early trial data similarly show meaningful proteinuria reductions, and the panel emphasizes interest in how response durability and tolerability compare across molecules in this therapeutic class. They note that ongoing phase 3 and extension studies for both agents will be crucial for determining optimal patient selection, sequencing, and real-world adoption.