Kidney Compass: New 2-Year APPLAUSE-IgAN Data for Iptacopan at WCN 2026

The treatment landscape for IgA nephropathy (IgAN) continues to evolve at a rapid pace, and new data presented at the World Congress of Nephrology (WCN) in Yokohama, Japan, suggest a potential shift in how clinicians approach disease modification in high-risk patients. In this episode of Kidney Compass, hosts Shikha Wadhwani, MD, MS, and Brendon Neuen, MBBS, PhD, spoke with Vlado Perkovic, MBBS, PhD, about newly presented 2-year eGFR slope data from the phase 3 APPLAUSE-IgAN trial evaluating iptacopan.

Perkovic explained that the trial built on previously published findings in the New England Journal of Medicine showing a 38% reduction in proteinuria at 9 months, but emphasized that the key question remained whether this would translate into long-term kidney protection. As he noted during the discussion, the study enrolled a particularly high-risk population, with median proteinuria around 1.7 g/g and rapid progression in the placebo arm—where eGFR declined by more than 6 mL/min/1.73 m² per year. Both hosts highlighted how this rate of decline reinforced the urgency for new therapies.

According to Perkovic, treatment with iptacopan slowed that decline to just over 3 mL/min/1.73 m² annually, representing an approximately 50% reduction compared with placebo and a treatment effect that exceeded initial expectations. Wadhwani and Neuen both pointed to this magnitude of benefit as especially compelling, particularly given that the trial was powered for a much smaller difference. Perkovic further noted that the key secondary composite endpoint, 30% eGFR decline or kidney failure, was reduced by 43%, which the hosts emphasized as evidence that the slope findings are likely to translate into meaningful clinical outcomes.

Safety was another focal point of the conversation. Perkovic noted that adverse events, serious adverse events, and discontinuations were comparable between groups, with no deaths reported. While he acknowledged a numerical increase in infections with iptacopan, he emphasized that all cases were manageable and resolved with treatment, and there was no concerning signal for severe or encapsulated infections.

The discussion then shifted to how iptacopan might fit into an increasingly complex treatment paradigm. Wadhwani raised the question of where complement inhibition would sit alongside existing therapies and evolving guideline recommendations, prompting Perkovic to stress that foundational treatments such as renin-angiotensin system inhibitors and SGLT2 inhibitors remain essential. However, he noted that patients receiving SGLT2 inhibitors in the trial still derived clear additional benefit, supporting the idea of combination therapy.

Neuen also highlighted the importance of understanding eGFR slope dynamics, asking whether acute versus chronic effects might influence interpretation of treatment benefit. In response, Perkovic explained that, unlike some other therapies, iptacopan did not appear to have an acute hemodynamic effect on eGFR, resulting in a more linear and interpretable slope over time, a point both hosts noted could simplify comparisons across agents.

Looking ahead, all three speakers emphasized the likelihood that combination approaches will be necessary, particularly for patients with high baseline proteinuria. As Perkovic pointed out during the exchange, achieving guideline-recommended targets may require multiple therapies with complementary mechanisms. Wadhwani further stressed the importance of earlier diagnosis and intervention, while Perkovic suggested that evolving data may prompt clinicians to reconsider biopsy thresholds and treatment timing.

Editors’ Note: Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and others. Relevant disclosures for Wadhwani include Boehringer Ingelheim, Calliditas Therapeutics, GSK, Otsuka Pharmaceutical Co., Travere Therapeutics, and others. Relevant disclosures for Perkovic include Boehringer Ingelheim,AbbVie, Inc., Bristol-Myers Squibb, servier, Astellas Pharma US, Merck, Janssen Pharmaceuticals, GSK, and others.