FDA Approves Novartis’ Vanrafia for Primary Immunoglobulin A Nephropathy

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The FDA approved Novartis' Vanrafia® (atrasentan), a selective endothelin A receptor antagonist, for reducing proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression. This once-daily, non-steroidal oral treatment can be added to supportive care, including renin-angiotensin system (RAS) inhibitors with-or-without sodium-glucose co-transporter-2 (SGLT2) inhibitors. The approval was granted based on data from the Phase III ALIGN study, which demonstrated that Vanrafia significantly reduced proteinuria at 36 weeks.¹

“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,” said Richard Lafayette, MD, FACP, professor of medicine, nephrology, director, Glomerular Disease Center at Stanford University Medical Center, and Vanrafia ALIGN study investigator and steering committee member, in a press release. “Vanrafia is a selective ETA receptor antagonist that effectively reduces proteinuria, a major risk factor in IgAN. Taking early, decisive action is critical to help improve outcomes for these patients who too often progress toward kidney failure.”

The global, randomized, multicenter, double-blind, placebo controlled, ALIGN study compared the efficacy and safety of Vanrafia versus placebo in 340 patients with biopsy-proven IgAN with baseline total proteinuria ≥1 g/day for an estimated 132 weeks. For the interim analysis, the primary endpoint is change in proteinuria as measured by 24-hour urine protein-to-creatinine ratio (UPCR) from baseline to 36 weeks. Secondary endpoints include evaluating the change in kidney function from baseline to 136 weeks.

Results found that Vanrafia achieved a 36.1% proteinuria reduction compared to placebo. Results were reported to be seen as early as week six and were sustained through week 36. Additionally, a group of patients treated with both a RAS inhibitor and an SGLT2 inhibitor demonstrated a 37.4% reduction in UPCR compared to placebo. However, the impact on kidney function decline has not yet been established, and continued approval is contingent upon confirming clinical benefits in the ongoing study.

Vanrafia demonstrated a favorable safety profile, which was consistent with previously reported data. Adverse events (AEs) were reported in over 2% of patients treated with Vanrafia, which was more frequent than placebo. The most common AEs included peripheral edema, anemia, and liver transaminase elevation.¹

According to Medscape, IgAN is found in approximately 10% of all biopsies in the United States. However, the prevalence in the United States is much lower than in Asia, where IgAN is found in 40% of all biopsies performed for glomerular disease. Additionally, the same is found in 20% of biopsies for glomerular disease in Europe. The highest prevalence rates have been reported in Singapore, Japan, Australia, Hong Kong, Finland, and southern Europe. The lowest rates have been reported in the United Kingdom, Canada, and the United States.²

“My son was diagnosed with IgA nephropathy long before there were any medicines approved to treat this condition, so the availability of multiple treatment options is incredibly meaningful for this community,” said Bonnie Schneider, director, co-Founder, IgA Nephropathy Foundation, in the press release. “The approval of Vanrafia broadens the treatment landscape and expands the opportunity to tailor care in a disease that can impact each patient so differently.”

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). Novartis. April 3, 2025. Accessed April 3, 2025. https://www.novartis.com/news/media-releases/novartis-receives-fda-accelerated-approval-vanrafia-atrasentan-first-and-only-selective-endothelin-receptor-antagonist-proteinuria-reduction-primary-iga-nephropathy-igan
2. IgA Nephropathy. Medscape. Accessed April 3, 2025. https://emedicine.medscape.com/article/239927-overview#a6