FDA Accelerated Approval for Vanrafiaatrasentan

This is generally defined as a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.  Vanrafia is a once-daily, non-steroidal, oral treatment that can be added onto supportive care, including a renin-angiotensin system (RAS) inhibitor with or without a sodium-glucose co-transporter-2 (SGLT2) inhibitor. 

Vanrafia was granted accelerated approval based on a prespecified interim analysis of the Phase III ALIGN study measuring the reduction of proteinuria at 36 weeks compared to placebo. It has not been established whether Vanrafia slows kidney function decline in patients with IgAN. The continued approval of Vanrafia may be contingent upon the verification of clinical benefit from the ongoing Phase III ALIGN study evaluating whether Vanrafia slows disease progression as measured by estimated glomerular filtration rate (eGFR) decline at week 136. The eGFR data are expected in 2026 and intended to support traditional FDA approval.

“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, M.D., F.A.C.P., Professor of Medicine, Nephrology and Director of the Glomerular Disease Center at Stanford University Medical Center, and Vanrafia ALIGN Study Investigator and Steering Committee Member. “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 towards kidney failure.

IgAN is a progressive, rare kidney disease in which the immune system attacks the kidneys, often causing glomerular inflammation and proteinuria. With almost 13 out of every million people in the US diagnosed per year, it is one of the most common autoimmune kidney diseases, and each person’s journey is unique. Up to 50% of IgAN patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis, often requiring maintenance dialysis and/or kidney transplantation, and response to treatment can vary.. Effective, targeted therapies with different mechanisms of action can help physicians select the most appropriate treatment for patients.

Data supporting approval; In the ongoing Phase III ALIGN study, patients receiving Vanrafia in combination with a RAS inhibitor achieved clinically meaningful and statistically significant proteinuria reduction of 36.1% (P<0.0001) compared to placebo, with results seen as early as week 6 and sustained through week 36. The effect of Vanrafia on UPCR was consistent across subgroups, including age, sex, race, and baseline disease characteristics, such as eGFR and proteinuria levels, in the main study cohort.. A similar treatment effect of Vanrafia was seen in an additional group of patients treated with both a RAS inhibitor and an SGLT2 inhibitor (37.4% reduction in UPCR vs. placebo).

The ALIGN study showed that Vanrafia has a favorable safety profile consistent with previously reported data. Adverse events reported in ≥2% of patients treated with Vanrafia, and more frequently than placebo, include peripheral edema, anemia, and liver transaminase elevation. Because some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity, and liver failure, clinicians should obtain liver enzyme testing before initiating Vanrafia and during treatment when clinically indicated. Vanrafia may cause serious birth defects. Vanrafia does not require a REMS program.