In a phase III trial, atrasentan reduced proteinuria by 36.1% in adults with immunoglobulin A nephropathy. Effects were observed as early as week 6 and were sustained through week 36.
The FDA has granted accelerated approval to atrasentan, a selective endothelin A receptor antagonist, for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for rapid disease progression, Novartis reported in a press release today. The therapy is indicated for patients with a urine protein-to-creatinine ratio of 1.5 g/g or more and is designed to be administered once daily in combination with standard supportive care, including renin-angiotensin system (RAS) inhibition, with or without a sodium-glucose co-transporter-2 (SGLT2) inhibitor. Vanrafia does not require a Risk Evaluation Mitigation Strategy program.
Accelerated approval was based on an interim analysis of the phase III ALIGN study. At week 36, patients who were randomized to atrasentan experienced a 36.1% reduction in proteinuria compared with those who received placebo (P < .0001). Reductions were observed by week 6 and were sustained through the primary analysis period. The treatment effect was consistent across key subgroups, including age, sex, race, baseline estimated glomerular filtration rate (eGFR), and proteinuria levels. In an additional cohort who received both an RAS inhibitor and an SGLT2 inhibitor, the proteinuria reduction with atrasentan was 37.4% vs placebo.
The safety profile of atrasentan was generally favorable and aligned with previous findings. Adverse events that occurred in 2% or more of patients and more frequently than with placebo included peripheral edema, anemia, and elevations in liver transaminases. Given the potential for hepatotoxicity, liver enzyme testing is recommended prior to initiation and periodically during treatment when clinically indicated. Atrasentan is contraindicated in pregnancy due to teratogenic risk.
Continued approval may depend on verification of clinical benefit in the ongoing ALIGN study, which is evaluating eGFR decline through week 136. These data are expected in 2026 and are intended to support traditional FDA approval.
IgAN is a chronic, immune-mediated glomerular disease with significant heterogeneity in progression. Persistent proteinuria is a key prognostic marker: up to 50% of patients progress to kidney failure within 10 to 20 years of diagnosis. The availability of disease-specific therapies may enable more targeted management approaches based on individual risk profiles.