Atrasentan (Vanrafia) Receives Accelerated Approval in IgA Nephropathy

The US Food and Drug Administration (FDA) has granted accelerated approval to atrasentan (Vanrafia), a once-daily, non-steroidal, oral treatment, for reducing proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression.

Announced by Novartis on April 02, 2025, the decision marks the FDA’s first approval for a selective endothelin A receptor antagonist for reducing protein in IgAN—adding to nephrology’s growing armamentarium of therapies. The approval also comes just 12 days after Novartis announced the historic approval of iptacopan (Fabhalta) as the first therapy approval for C3G glomerulopathy.1,2

“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, professor of medicine in Nephrology and director of the Glomerular Disease Center at Stanford University Medical Center, and Vanrafia ALIGN Study Investigator and Steering Committee Member.1 “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.”

According to labeling information, atrasentan can be added to a renin-angiotensin system (RAS) inhibitor with or without a sodium-glucose co-transporter-2 (SGLT2) inhibitor. Additionally, there is no requirement for a Risk Evaluation Mitigation Strategy (REMS) program for use.1

The accelerated approval is based on 36-week data from the ongoing ALIGN trial—a global phase 3 study evaluating the efficacy and safety of atrasentan in patients with IgA nephropathy at high risk of kidney function loss. The 132-week trial enrolled 340 patients who received either atrasentan (0.75 mg daily) or placebo alongside their baseline medications, which included maximally tolerated RAS inhibitors and could include SGLT2 inhibitors.1,3
The trial’s primary outcome of interest was the change in urine protein to creatinine ratio (UPCR), based on 24-hour urine collection, from baseline.3

Primary results indicated use was associated with a 36.1% (95% CI, -44.6 to -26.4; P < .0001) reduction in UPCR at week 36 relative to placebo therapy, with reductions as early as the first 6 weeks of treatment. Data published in the New England Journal of Medicine detail a geometric mean UPCR of 1450.2 mg/g at baseline to 882.2 mg/g (-38.1%; 95% CI, -43.9 to -31.7) in the atrasentan group. In comparison, the placebo group experienced a reduction from 1484.3 mg/g to 1374.8 mg/g (-3.1%; 95% CI, -12.4 to 7.3).3

In the approval announcement, Novartis noted eGFR data are expected in 2026 and intended to support traditional FDA approval.1

“We are proud to expand the treatment landscape in IgA nephropathy with today’s FDA accelerated approval of Vanrafia. IgAN is a heterogenous condition that requires differentiated therapies with unique mechanisms of action, and with our multi-asset kidney disease portfolio, we are well positioned to support a broad patient population and advance care for this disease,” said Victor Bultó, president of Novartis US.1

References:

1. Novartis. 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 United States of America. Published April 2, 2025. Accessed April 2, 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. Novartis. Novartis receives third FDA approval for oral Fabhalta® (iptacopan) – the first and only treatment approved in C3 glomerulopathy (C3G). GlobeNewswire. March 20, 2025. Accessed March 20, 2025. https://www.globenewswire.com/news-release/2025/03/20/3046800/0/en/Novartis-receives-third-FDA-approval-for-oral-Fabhalta-iptacopan-the-first-and-only-treatment-approved-in-C3-glomerulopathy-C3G.html.

3. Heerspink HJL, Jardine M, Kohan DE, et al. Atrasentan in Patients with IgA Nephropathy. N Engl J Med. 2025;392(6):544-554. doi:10.1056/NEJMoa2409415