Long-term kidney protection in IgA nephropathy with atrasentan

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Clinical drug development in IgA nephropathy (IgAN) has expanded rapidly, and new drug classes being tested in clinical trials include endothelin receptor A (ETA) antagonists. Long-term data from the ALIGN clinical trial, presented at the 63rd European Renal Association Congress in Glasgow, confirm the renoprotective potential and safety of the selective endothelin receptor antagonist atrasentan as a non-immunosuppressive treatment in IgAN.

An interim analysis of the main cohort of 340 patients had shown no difference in eGFR between groups at 36 weeks, which also demonstrated that atrasentan did not cause an acute reduction in eGFR. However, over the full trial period, eGFR declined by 7.5 ml/min/1.73 m2 in the atrasentan group versus 9.9 ml/min/1.73 m2 in the placebo group. The difference between the two groups was clinically meaningful (2.4 ml/min/1.73 m2), although not statistically significant (P = 0.057). In the SGLT2 subgroup, the change in eGFR from baseline at week 136 was –1.5 ml/min/1.73 m2 in the treatment group and –10.6 ml/min/1.73 m2 in the placebo group. Of note, in this subgroup, the average baseline eGFR was higher in the atrasentan group (57.4 ml/min/1.73 m2) than in the placebo group (48.6 ml/min/1.73 m2).