The most consequential number arriving at ERA 2026 is not a p-value but a duration: 2.5 years of eGFR data from the ALIGN trial of atrasentan in IgA nephropathy. Longitudinal kidney function trajectories are the functional currency of nephrology — short-term proteinuria responses are mechanistically plausible but regulatorily insufficient, and a 2.5-year eGFR slope in a hard-to-enroll immune-mediated disease is the kind of evidence that moves prescribing behavior and informs label negotiations simultaneously.
The APPLAUSE-IgAN final data for iptacopan carry comparable weight, specifically the prespecified subgroup analysis showing near-normal kidney function decline. Subgroup findings in Phase III are usually exploratory noise, but when they are prespecified and consistent with the agent’s complement-targeting mechanism, they function as precision-medicine scaffolding — identifying which patients experience durable stabilization rather than transient biochemical shifts. That matters enormously for payers constructing prior-authorization criteria and for clinicians deciding between iptacopan and atrasentan in a disease where two approved mechanistically distinct agents now compete head-to-head in clinical practice without a randomized comparison.
Zigakibart’s 124-week Phase I/II data extend the anti-APRIL story into genuine durability territory. Most anti-APRIL and BAFF-targeting programs in IgAN have shown steep early responses in proteinuria that flatten or regress; 124 weeks of safety and efficacy data will reveal whether zigakibart sustains its effect or follows that pattern. The APPRISE-C3G real-world platform for iptacopan in C3 glomerulopathy and the farabursen Phase III design disclosure in ADPKD both underscore that Novartis is constructing a portfolio-level presence across rare complement-driven nephropathies rather than defending a single franchise — a structurally different competitive posture than any single-asset player in this space.
The one marker that will define the clinical narrative emerging from Glasgow is the absolute eGFR slope in the ALIGN 2.5-year data. If atrasentan demonstrates a slope meaningfully superior to historical standard-of-care benchmarks — roughly minus 1.5 to 2 mL/min/1.73m² per year in treated IgAN cohorts — it shifts the endpoint conversation for every subsequent nephrology trial from proteinuria surrogates toward function preservation as the primary efficacy standard.
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.
