FDA Approves Atrasentan for Proteinuria Reduction in Primary IgA Nephropathy

Patients requiring treatment for proteinuria reduction in primary immunoglobulin A (IgA) nephropathy now have a solution, with the FDA's accelerated approval of atrasentan (Vanrafia; Novartis)..1 Atrasentan is a selective endothelin A (ETA) receptor antagonist that can be taken orally once per day in addition to other supportive care.

Primary IgA nephropathy is a disease where IgA protein builds up in the kidneys, damaging them.2 The condition can be diagnosed through urine tests, where elevated protein may be found. The condition affects approximately 13 of every 1 million people living in the US. Persistent proteinuria can cause kidney failure within 10 to 20 years of diagnosis in up to 50% of those diagnosed with IgA nephropathy. This makes proteinuria reduction a key method of helping to preserve the kidneys, along with controlling blood pressure and cholesterol.

Astrasentan aims to cover this aspect of treatment for individuals living with primary IgA nephropathy by inhibiting the binding of endothelin A to the endothelin system, as endothelin is found to be increased in various kidney diseases. The treatment aims to reverse the methods by which endothelin contributes to proteinuria.3

This approval comes as a result of the phase 3 ALIGN (NCT04573478) study that aimed to measure proteinuria in patients using atrasentan vs a placebo. The global, randomized, double-blind, multicenter trial included patients with IgA nephropathy who were at risk of losing their kidney function. Patients with total proteinuria of 1 or more grams per day who had proven IgA nephropathy were included in the study and randomized to either the placebo or oral atrasentan 0.75 mg once daily.

Atrasentan will help patients with primary IgA nephropathy manage their proteinuria | Image credit: Crystal light - stock.adobe.com

There were 340 patients who were randomized 1:1 into these 2 groups and an additional 64 patients who were receiving an sodium-glucose cotransporter-2 (SGLT2) inhibitor for at least 12 weeks who were also enrolled. Change in proteinuria acted as the primary objective with change in kidney function acting as the secondary end point.

Patients who were taking atrasentan saw a reduction of their proteinuria by 36.1% compared with placebo through 36 weeks. These results were consistent across all subgroups. Patients who were taking SGLT2 inhibitors also saw a 37.4% reduction in proteinuria compared with placebo. Peripheral edema, anemia, and liver transaminase were all reported adverse effects of atrasentan and were reported in approximately 2% of the participants.

"Today's approval marks an important milestone for people living with IgA nephropathy, offering a new option that can be seamlessly integrated into their existing treatment plan, with no REMS requirement,"Richard Lafayette, MD, FACP, professor of medicine, Nephrology; director of the Glomerular Disease Center at Stanford University Medical Center; and Vanrafia ALIGN study investigator and steering committee member, said in a statement.1

References

1. Novartis receives FDA accelerated approval for Vanrafia (atrasentan), the first and only selective endothelin A receptor antagonist for proteinuria reduction in primary IgA nephropathy (IgAN). News release. Novartis; April 3, 2025. Accessed April 3, 2025. https://www.novartis.com/us-en/news/media-releases/novartis-receives-fda-accelerated-approval-vanrafia-atrasentan-first-and-only-selective-endothelin-receptor-antagonist-proteinuria-reduction-primary-iga-nephropathy-igan
2. Immunoglobulin A nephropathy. Johns Hopkins Medicine. Accessed April 3, 2025. https://www.hopkinsmedicine.org/health/conditions-and-diseases/immunoglobulin-a-iga-nephropathy
3. Martínez-Díaz I, Martos N, Llorens-Cebrià C, et al. Endothelin receptor antagonists in kidney disease. Int J Mol Sci. 2023;24(4):3427. doi:10.3390/ijms24043427