The most consequential number arriving at ERA 2026 is not a p-value — it is 2.5 years. That is how long the ALIGN trial tracked eGFR trajectories under atrasentan in IgA nephropathy, and the late-breaking oral presentation on June 4 will show whether the proteinuria reductions that earned Vanrafia its approval translate into durable kidney-function preservation at a duration regulators and nephrologists actually care about. Short-term urine protein-to-creatinine ratio improvements are mechanistically plausible; sustained eGFR slope attenuation over 30 months is the harder, more clinically meaningful claim.
The APPLAUSE-IgAN final data for iptacopan add a second stress test to the same question. Complement pathway inhibition via the alternative route has a coherent rationale in IgAN, but the prespecified subgroup analysis being presented — framed around near-normal kidney function decline — signals that Novartis is pushing beyond aggregate trial-level effects into identifying which patients get the most benefit. That granularity matters enormously for label negotiations and real-world prescribing guidance. IgAN is a heterogeneous disease; a subgroup signal that survives final-data scrutiny could reshape how nephrologists sequence iptacopan relative to atrasentan rather than treating the two as interchangeable.
Zigakibart, Novartis’s anti-APRIL investigational antibody, reaches 124 weeks of Phase I/II follow-up — an unusually extended window for an asset still in early-stage development. Anti-APRIL sits upstream of the IgA glycosylation cascade that drives mesangial deposition, making it mechanistically distinct from both endothelin-A antagonism and complement inhibition. At 124 weeks, the critical question is whether the effect on galactose-deficient IgA1 levels and proteinuria is durable or attenuates with prolonged treatment. The farabursen Phase III design disclosure for ADPKD rounds out a portfolio that now spans four distinct mechanistic classes across two rare kidney diseases — an unusual breadth for a single sponsor at a single congress.
The single marker worth tracking from these ERA presentations is the eGFR slope data from ALIGN at 2.5 years. If atrasentan demonstrates a statistically and clinically meaningful preservation of kidney function — not just proteinuria reduction — at that duration, it substantially strengthens the case for early intervention in IgAN before irreversible fibrosis accumulates, and will directly pressure competitor programs to match that endpoint bar in their own registrational designs.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
