IgAN data in The Lancet show clinically meaningful slowing of kidney function decline with Vanrafia (atrasentan) over 2.5 years – Novartis
Novartis reported final 2.5-year Phase III ALIGN results showing slower kidney function decline with Vanrafia (atrasentan) versus placebo in adults with IgA nephropathy (IgAN). Results were published in The Lancet and presented at the European Renal Association (ERA) Congress. Estimated glomerular filtration rate (eGFR) change from baseline favored Vanrafia, alongside sustained reductions of protein in the urine through end of treatment. Benefits were consistent across different measures of kidney function and in patients additionally receiving sodium-glucose co-transporter-2 (SGLT2) inhibitors.
“These results provide robust evidence of clinically meaningful slowing of kidney function decline over more than two years of treatment, reinforcing findings from the earlier analysis of proteinuria reduction,” said Richard Lafayette, MD, FACP, Professor of Medicine, Nephrology, Director of the Glomerular Disease Center at Stanford University Medical Center, and ALIGN Study Investigator and Steering Committee Member. “They highlight the role of a highly selective endothelin A receptor antagonist as part of an evolving treatment approach for IgAN.”
“ALIGN reinforces Vanrafia’s potential as a foundational IgAN therapy and our commitment to advancing long-term kidney protection through continued innovation,” said Ruchira Glaser, MD, MS, Global Head, Cardiovascular, Renal and Metabolic Development, Novartis. “Together with our broader portfolio, these data strengthen confidence in an evidence-based approach to managing this progressive disease.”
Safety was consistent with prior studies, with adverse events similar to placebo and no new signals observed.
Vanrafia received accelerated approval in the U.S. and China for reduction of proteinuria in adults with IgAN in 2025. Novartis intends to use these data to support submission for traditional approval in 2026.
About ALIGN
The ALIGN study (NCT04573478) is a global, randomized, multicenter, double-blind, placebo-controlled Phase III clinical trial comparing the efficacy and safety of Vanrafia vs placebo in patients with IgAN at risk of progressive loss of kidney function. In total, 340 patients with biopsy-proven IgAN with baseline total proteinuria ≥1 g/day despite optimized renin-angiotensin system (RAS) inhibitor treatment were randomized to receive once-daily, oral Vanrafia (0.75 mg) or placebo for approximately 132 weeks. Patients continue receiving a maximally tolerated and stable dose of a RAS inhibitor as supportive care. An additional cohort of 64 patients receiving an SGLT2 inhibitor in addition to RAS inhibitor for at least 12 weeks was also enrolled. The primary efficacy endpoint for the interim analysis (in 270 patients) was change in protein in urine, as measured by 24-hour UPCR from baseline to 36 weeks. The key secondary endpoint for the final analysis is the change from baseline to 136 weeks in kidney function as measured by eGFR. Other secondary efficacy endpoints as well as safety and tolerability are also assessed.
Citation: Atrasentan in patients with IgA nephropathy (ALIGN): final 2·5-year results from a randomised, double-blind, placebo-controlled, phase 3 trial. Authors: Prof Hiddo J L Heerspink, PhDa ∙ Prof Meg J Jardine, PhDb, ∙ Prof Donald E Kohan, MD et al. The Lancet. Published online June 4, 2026. DOI: 10.1016/S0140-6736(26)00960-8
