Interim Analysis Finds Atrasentan Reduces Proteinuria in IgA Nephropathy

Results of a prespecified interim analysis of the phase 3 ALIGN study of atrasentan presented at the 61st European Renal Association Congress found that the drug demonstrated a statistically significant 36.1% (P<.0001) proteinuria reduction compared with placebo and supportive care with a renin-angiotensin system (RAS) inhibitor at 36 weeks in patients with IgA nephropathy (IgAN).

The ALIGN study includes 340 patients with biopsy-proven IgAN with baseline total proteinuria ≥1 g/day despite optimized RAS inhibitor treatment. Participants were randomized to receive oral atrasentan (0.75 mg) once daily or placebo for approximately 2.5 years (132 weeks). Participants continue to receive a maximally tolerated and stable dose of a RAS inhibitor as supportive care (unless they cannot tolerate RAS inhibitor therapy). An additional group of 64 enrolled patients receiving a stable dose of sodium-glucose cotransporter 2 (SGLT2) inhibitor as background care for at least 12 weeks have also been enrolled. The primary end point is change in proteinuria as measured by 24-hour urine protein-to-creatinine ratio from baseline to 36 weeks.

ALIGN will continue in a blinded manner, and final results are expected in 2026. These results will include the secondary endpoint, which is change from baseline in estimated glomerular filtration rate at 136 weeks, and the exploratory SGLT2 cohort.

Atrasentan is an investigational oral endothelin A (ETA) receptor antagonist. Activation of the ETA receptor contributes to elevated proteinuria, which is associated with kidney damage, fibrosis, and loss of kidney function in IgAN. Atrasentan is currently in phase 3 development for IgAN and in early-stage development for other rare kidney diseases. Drug maker Novartis plans to submit atrasentan for US Food and Drug Administration approval during the first half of 2024.

Source: Heerspink HJL, Jardine M, Kohan D, et al. ALIGN phase 3 primary endpoint analysis: atrasentan shows significant reduction in proteinuria in patients with IgA nephropathy. Presented at the 61st European Renal Association Congress; May 23-26, 2024; Stockholm, Sweden.