Phase 2b and Phase 3 ORIGIN Trials of Atacicept in IgAN

This segment centers on the clinical development of atacicept, a BAFF/APRIL–pathway inhibitor designed to reduce the upstream production of galactose-deficient IgA1. The panel first reviews the phase 2b ORIGIN trial, which showed significant and sustained reductions in proteinuria alongside consistent suppression of disease-relevant immunologic biomarkers. These results helped confirm the mechanistic rationale for targeting the mucosal B-cell activation pathway and supported advancement to phase 3 evaluation. The discussion then transitions to the phase 3 ORIGIN data, recently presented at ASN Kidney Week 2025, which reinforced the proteinuria-lowering effects observed in phase 2b. The panel notes that the proteinuria findings are clinically meaningful and align with the current understanding of proteinuria as a predictor of long-term disease risk. They highlight that longer-term follow-up and extension analyses will be important to understand durability and safety.