Since the 2025 IgA nephropathy (IgAN) guideline update, three major therapies have reshaped the treatment landscape. Atrasentan, an endothelin A receptor antagonist, received accelerated approval for patients at high risk of progression (uPCR ≥1.5 g/g) based on the ALIGN trial. Added on top of RAS inhibition, it achieved a 38.1% reduction in proteinuria versus 3.1% with placebo, a significant 36.1% treatment difference.
Later in 2025, sibeprenlimab, an anti-APRIL monoclonal antibody targeting B-cell–mediated IgA production, was approved following the VISIONARY trial. It demonstrated a 50.2% reduction in proteinuria versus a 2.1% increase with placebo (difference 51.2%). Importantly, it also showed robust biologic effects, reducing pathogenic Gd-IgA1 by ~70% along with significant reductions in total IgA, IgM, and IgG.
Most recently, iptacopan, a complement factor B inhibitor, showed strong long-term outcomes. Over two years, it significantly slowed eGFR decline and reduced kidney failure events (HR 0.57), with an overall safety profile similar to placebo, though with higher rates of serious infections.
Together, these therapies target distinct pathways—hemodynamic, immunologic, and complement—marking a new era of mechanism-driven IgAN treatment.
Here is the most recent KDIGO update
Above cartoon was created using AI for illustrating a battle of the new class of agents for IgAN treatment
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