Novartis ALIGN data show Vanrafia slows IgAN kidney decline by 34%
Novartis has reported final Phase III results from its ALIGN study of Vanrafia (atrasentan) in IgA nephropathy (IgAN), showing a clinically meaningful slowing of kidney function decline over 132 weeks of treatment. The data were published simultaneously in The Lancet and presented at the European Renal Association Congress in Glasgow on 4 June 2026.
The headline efficacy figure from the supportive eGFR slope analysis showed an approximately 34% reduction in the annualised rate of kidney function decline with Vanrafia versus placebo (−2.7 vs −4.1 mL/min/1.73 m²/year; p=0.003). On the key secondary endpoint — change from baseline in eGFR at end of treatment (Week 132) — Vanrafia patients lost 6.9 mL/min/1.73 m² compared with 9.5 mL/min/1.73 m² in the placebo arm, a difference of 2.6 (p=0.039). The primary end-of-study comparison at Week 136, which included a four-week off-treatment follow-up, did not reach nominal significance (p=0.057), a nuance that investors and clinicians will note when reading the full dataset.
Clinical detail and subgroup findings
Proteinuria reduction, measured by urine protein-to-creatinine ratio (UPCR), showed a 38.3% relative reduction with Vanrafia versus placebo at nine months, sustained through to Week 132 at a 28.4% relative reduction. In a separate cohort of 64 patients who were also receiving SGLT2 inhibitors alongside standard renin-angiotensin system (RAS) inhibitor therapy, the benefit was more pronounced: an eGFR change of −1.5 versus −10.6 mL/min/1.73 m² in favour of Vanrafia at Week 136 (p=0.004). The consistency of effect across background therapies is likely to feature prominently in Novartis's regulatory submission.
Richard Lafayette, Professor of Medicine at Stanford University Medical Center and an ALIGN steering committee member, said the 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."
Safety was consistent with earlier studies; adverse event rates were similar to placebo and no new signals were identified. Novartis said Vanrafia does not require a Risk Evaluation and Mitigation Strategy programme, which simplifies prescribing logistics compared with some other endothelin receptor antagonists in the class.
Regulatory path and competitive landscape
Vanrafia received accelerated approval in the United States and China in 2025 on the basis of proteinuria reduction. Novartis intends to use the ALIGN final data to support a traditional approval submission in the US in 2026, a conversion that would remove the requirement for a post-marketing confirmatory trial and solidify the product's commercial position.
The IgAN treatment landscape has expanded significantly in the past three years, moving from a field dominated by supportive care — RAS inhibitors and corticosteroids — to one with multiple targeted agents. Novartis's own portfolio also includes Fabhalta (iptacopan), a complement pathway inhibitor that received approval for IgAN in 2025 on Phase III data published in the New England Journal of Medicine. Separately, Calliditas Therapeutics' targeted-release budesonide (Tarpeyo/Kinpeygo) and HZNP-linked sparsentan are among the agents reshaping standard of care. The emergence of SGLT2 inhibitors as a backbone therapy — supported by the ALIGN subgroup findings — adds further complexity to treatment sequencing decisions.
IgAN affects an estimated 25 people per million worldwide annually. Up to half of patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis. With few historically approved options and a growing evidence base, the indication is attracting sustained industry investment, and further combination-therapy data across the approved and investigational agents are expected over the next 12 to 18 months.