Approved therapies in the IgA nephropathy armamentarium: a summary of the evidence

Historically, IgA nephropathy (IgAN) was managed using supportive care, with a suggested 6 months of immunosuppressive therapy considered for patients at high risk of progressive kidney function decline (proteinuria, >0.75-1 g/d) despite ≥90 days of optimized supportive care. The evolving treatment landscape includes agents that target immunologic aspects of IgAN or better preserve kidney function, or both. Recent approvals include Nefecon, sparsentan, iptacopan, atrasentan, and sibeprenlimab. Nefecon, a targeted-release formulation of budesonide, is the only US Food and Drug Administration and European Medicines Agency fully approved agent that is designed to target the primary source of IgAN: galactose-deficient IgA1 production in the gut mucosa. Phase 3 data showed that Nefecon slowed estimated glomerular filtration rate decline and decreased proteinuria versus placebo, with an acceptable safety profile. Sparsentan, a fully US Food and Drug Administration- and European Medicines Agency-approved dual endothelin A/angiotensin II receptor antagonist, affects the generic responses to IgAN-induced nephron loss, potentially including glomerular inflammation and fibrosis. Sparsentan demonstrated a significant reduction in proteinuria and estimated glomerular filtration rate decline compared with irbesartan. Iptacopan inhibits complement factor B and has received accelerated US Food and Drug Administration approval. Interim phase 3 study data have shown that iptacopan significantly reduces proteinuria when compared with placebo. The endothelin A receptor antagonist atrasentan and A proliferation binding ligand inhibitor sibeprenlimab have also received accelerated US Food and Drug Administration approval, based on interim phase 3 results showing significant proteinuria reduction versus placebo in patients with IgAN. This expanded clinical armamentarium offers clinicians and patients greater choice and improved disease control in IgAN management.