One-Year Results of the AFFINITY Study of Atrasentan in Patients With IgAN

The AFFINITY study (NCT04573920) is a phase 2, open-label basket trial of atrasentan in patients with kidney disease. The primary study end point was change in 24-hour urine protein-to-creatinine ratio (UPCR) from baseline to week 12. Atrasentan is a potent, selective endothelin A receptor antagonist used to treat IgA nephropathy (IgAN) and other kidney diseases. Researchers reported 1-year results during the National Kidney Foundation Spring Clinical Meetings 2025.

The study cohort included adults with biopsy-proven IgAN. Eligible participants had estimated glomerular filtration rate of 30 mL/min/1.73 m² or greater and urine protein-creatinine ratio (UPCR) 0.5 g/g or greater and less than 1 g/g, measured at the first morning void at screening and were receiving maximum tolerated/stable renin-angiotensin system inhibitors for 12 weeks or more. Patients received 0.785 mg oral atrasentan daily for 52 weeks.

Among 20 patients with IgAN, median age was 44.5 years, 50% were women, 45% were White, and 45% were Asian. Median 24-hour UPCR was 0.8 g/g; 12 patients had baseline UPCR of less than 1 g/g.

By week 6, there was an evident reduction in UPCR, which was sustained through week 52. In patients with baseline UPCR less than 1 g/g and in those with UPCR 1 g/g or greater, there were clinically meaningful reductions in UPCR through week 52. At baseline, week 12, and week 24, 5% (1 of 20), 60% (12 of 20), and 68% (13 of 19) of patients, respectively, had UPCR less than 0.5 g/g.

One patient discontinued treatment at week 13 due to a headache considered to be treatment related. No treatment-related serious adverse events or deaths were reported.

In summary, the researchers said, “Atrasentan was well tolerated and resulted in a stable, clinically meaningful reduction in proteinuria over 1 year of treatment, comparable between patients with baseline UPCR less than <1 and ≥1 g/g.”

Source: Barratt J, Vo ND, Lee S, et al. AFFINITY study: 1y results of atrasentan in IgAN in patients with UPCR <1 and ≥1g/g. Abstract #G-447. Presented at the National Kidney Foundation Spring Clinical Meetings 2025; April 10-13, 2025; Boston, MA. doi:10.1053/j.ajkd.2025.02.448