Novartis Secures FDA Accelerated Approval for Vanrafia, a Novel Treatment for Proteinuria in IgA Nephropathy

Novartis has received accelerated approval from the U.S. Food and Drug Administration (FDA) for Vanrafia (atrasentan), a highly selective endothelin A (ETA) receptor blocker designed to lower proteinuria in individuals with primary immunoglobulin A nephropathy (IgAN). This medication serves as an additional therapy to standard supportive care and does not require a Risk Evaluation and Mitigation Strategy (REMS) program.

A Phase III clinical trial demonstrated that atrasentan led to a 36.1% reduction in proteinuria compared to a placebo. Improvements became evident as early as six weeks into treatment and were sustained through 36 weeks, all while maintaining a favorable safety profile.

IgAN is a progressive and uncommon kidney disorder. Among patients who continue to experience high protein levels in their urine, up to half may advance to kidney failure within one to two decades after diagnosis.

This approval marks the third time in under a year that the FDA has cleared a Novartis renal treatment, reinforcing the company's leadership in transforming kidney disease management.

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Atrasentan is an oral, non-steroidal treatment taken once daily. It is intended for patients with IgAN who are at risk of rapid disease progression, typically characterized by a urine protein-to-creatinine ratio (UPCR) of 1.5 g/g or higher. It can be administered alongside renin-angiotensin system (RAS) inhibitors, with or without sodium-glucose co-transporter-2 (SGLT2) inhibitors.

The FDA granted accelerated approval based on an interim analysis from the ongoing Phase III ALIGN study, which assessed the medication’s ability to reduce proteinuria over 36 weeks. While the long-term impact on kidney function is yet to be confirmed, the drug’s continued approval will depend on further clinical trials demonstrating its effectiveness in slowing disease progression. Final results on estimated glomerular filtration rate (eGFR) changes are expected in 2026, which could support full FDA approval.

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IgAN is an autoimmune condition where the immune system mistakenly damages the kidneys, often leading to inflammation and proteinuria. Approximately 13 in every million people in the U.S. are diagnosed with this disease annually, making it one of the most prevalent autoimmune kidney disorders. The disease course varies among individuals, and many patients who do not respond adequately to treatment may require long-term dialysis or kidney transplantation.

Findings from the ALIGN study indicated that patients using atrasentan in combination with RAS inhibitors experienced significant proteinuria reductions of 36.1% compared to placebo, with improvements observed as early as week six and continuing through week 36.

The drug’s impact was consistent across demographic and clinical subgroups, including age, sex, race, baseline kidney function, and proteinuria levels.

In another study group where patients received both a RAS inhibitor and an SGLT2 inhibitor, atrasentan achieved a 37.4% reduction in proteinuria compared to placebo.

Safety data from the ALIGN trial suggest that atrasentan is well tolerated, aligning with prior research. The most frequently reported side effects (occurring in at least 2% of patients and more often than in the placebo group) included peripheral swelling, reduced red blood cell count, and increased liver enzymes. Since certain endothelin receptor blockers have been associated with liver enzyme elevations and, in rare cases, liver failure, healthcare providers are advised to monitor liver function before and during treatment as necessary. Additionally, atrasentan carries a risk of serious birth defects and should be used with caution in women of childbearing potential. Unlike some similar medications, atrasentan does not require a REMS program.

With its latest FDA approval, Novartis continues to advance its renal portfolio, providing new options for patients with IgAN and reinforcing its commitment to innovation in kidney disease management.