Novartis Reports Final Phase 3 ALIGN Kidney Function Data for Vanrafia in IgA Nephropathy

Novartis on February 13 reported final results from the Phase 3 ALIGN study of Vanrafia (atrasentan) in IgA nephropathy, saying the data support a slowing of kidney function decline, and that it plans to seek traditional FDA approval for the drug this year, according to the company's release.

At Week 136, four weeks after study treatment ended, patients on Vanrafia showed a difference of 2.39 ml/min/1.73m2 in estimated glomerular filtration rate (eGFR) change from baseline compared with placebo, with a two-sided p-value of 0.057. The results are company-reported; Novartis did not describe the Week 136 result as statistically significant.

What the trial measured

ALIGN is a global, randomized, double-blind, placebo-controlled Phase 3 trial that randomized 340 adults with biopsy-proven IgA nephropathy and at least 1 g a day of protein in the urine, despite optimized treatment with a renin-angiotensin system inhibitor, to once-daily oral Vanrafia 0.75 mg or placebo for about 132 weeks. A separate cohort of 64 patients also taking an SGLT2 inhibitor was enrolled.

The study's primary endpoint, measured at an interim analysis, was the change in proteinuria at 36 weeks. That result was the basis for the FDA's accelerated approval of Vanrafia in April 2025 for reducing proteinuria in adults with primary IgA nephropathy at risk of rapid progression. In its release on that approval, Novartis reported a 36.1% reduction in proteinuria versus placebo and said it had not been established whether the drug slows kidney function decline. It said continued approval might depend on the eGFR results at Week 136, which it then expected in 2026 to support traditional approval.

Change in eGFR from baseline to Week 136 is the key secondary endpoint of the final analysis. At the end of treatment, at Week 132, the difference versus placebo was 2.59 ml/min/1.73 m2, which Novartis reported with a nominal two-sided p-value of 0.039. The company said results favored Vanrafia across multiple timepoints and measures of kidney function, and in the exploratory group of patients also receiving SGLT2 inhibitors. Novartis said safety was consistent with previous findings.

Regulatory plans

"We are pleased with today's Phase III ALIGN results, which add to the growing evidence of Vanrafia as a potential foundational therapy to slow kidney function decline," said Ruchira Glaser, global head of Novartis' cardiovascular, renal and metabolic development unit.

Vanrafia, a selective endothelin A receptor antagonist, received accelerated approval in the U.S. and China in 2025. Novartis said ALIGN provides the longest follow-up period of any pivotal Phase 3 study in IgA nephropathy. The company is also developing Fabhalta (iptacopan) and the investigational antibody zigakibart for the disease.

IgA nephropathy is a progressive autoimmune kidney disease. Novartis said up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis.