FDA

Vanrafia approved for IgA nephropathy

April 9, 2025

Brand name: Vanrafia

Generic name: atrasentan

Manufacturer: Novartis

Approval date: April 3, 2025

FDA granted accelerated approval to Vanrafia (atrasentan) for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression (generally defined as a urine protein-to-creatinine ratio [UPCR] ≥1.5 g/g).

According to a manufacturer press release, Vanrafia is a once-daily, non-steroidal oral treatment that can be added to supportive care, including a renin-angiotensin system (RAS) inhibitor with or without an SGLT2 inhibitor.

Efficacy

Accelerated approval was based on data from the randomized, double-blind, placebo-controlled ALIGN trial (NCT04573478), which enrolled adults with biopsy-proven primary IgAN, an eGFR ≥30mL/min/1.72m², and a urine protein of ≥1g/day on a stable dose of maximally tolerated RAS inhibitor. The study included two cohorts: a main cohort of 340 patients and an exploratory cohort of 64 patients who were also on a stable dose of an SGLT2 inhibitor at baseline. Patients with CKD due to another condition in addition to IgAN or those who’d been recently treated with systemic immunosuppressants were excluded. Patients were randomized (1:1) to receive either Vanrafia 0.75 mg or placebo once daily. RAS inhibitor therapy was continued throughout the study. Rescue immunosuppressive treatment could be initiated per investigator discretion during the trial.

The efficacy analysis included the first 270 patients in the main cohort who reached the week 36 visit. The primary endpoint was the percent reduction in UPCR at week 36 relative to baseline. Participants receiving Vanrafia in combination with a RAS inhibitor achieved a statistically significant proteinuria reduction of 36.1% (P<0.0001) compared with placebo. The effect on UPCR was consistent across subgroups, including age, sex, race, and baseline disease characteristics, as well as in the exploratory SGLT1 inhibitor cohort (37.4% reduction in UPCR vs. placebo).

Safety

The most common adverse reactions (incidence ≥5%) were peripheral edema and anemia.

Recommended dose

The recommended dosage of Vanrafia is 0.75 mg PO once daily with or without food.

Sources:

Vanrafia (atrasentan) [package insert]. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219208s000lbl.pdf Revised April 2025. Accessed April 8, 2025.

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]. 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