Final 2.5-Year Phase 3 ALIGN Results Show Atrasentan Slows Kidney Function Decline in IgA Nephropathy

Final 2.5-Year Phase 3 ALIGN Results Show Atrasentan Slows Kidney Function Decline in IgA Nephropathy

On June 4, 2026, final 2.5-year data from the landmark Phase 3 ALIGN (NCT04573478) trial was published in The Lancet and presented at the 63rd European Renal Association (ERA) Congress. The results demonstrate that Novartis's Vanrafia (atrasentan)—a highly selective oral endothelin A (ETA) receptor antagonist—significantly slows the decline of kidney function in adults with immunoglobulin A nephropathy (IgAN) who are at high risk of progressive kidney failure.

Atrasentan previously received accelerated approval in the United States and China in 2025 based on positive 36-week interim data showing a robust reduction in proteinuria.¹ Novartis intends to use these final 2.5-year results to support submissions for full (traditional) regulatory approval in late 2026.

Study Design and Patient Population

The ALIGN trial enrolled 340 patients with biopsy-proven IgAN and baseline total proteinuria ≥1 g/day despite receiving optimized, maximally tolerated stable doses of renin-angiotensin system (RAS) inhibitors. Participants were randomized 1:1 to receive either once-daily oral atrasentan (0.75 mg) or placebo for 132 weeks, followed by a 4-week off-treatment safety follow-up.

An additional cohort of 64 patients who were already receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors in addition to RAS inhibitors was also evaluated, demonstrating that atrasentan's therapeutic benefits are additive and consistent even in patients on modern combination regimens.

Key Efficacy Findings

The primary endpoint of the interim analysis (proteinuria reduction) was previously met. The key secondary endpoint of the final analysis was the change in kidney function, measured by estimated glomerular filtration rate (eGFR) from baseline to week 136:

• eGFR Decline at Week 136: In the atrasentan arm, the change from baseline in eGFR was –7.5 mL/min/1.73 m² (95% CI: –9.2 to –5.8), compared to –9.9 mL/min/1.73 m² (95% CI: –11.7 to –8.1) in the placebo arm.
• Between-Group Difference: The difference favored atrasentan by 2.4 mL/min/1.73 m² (95% CI: –0.1 to 4.8; p-value = 0.057).
• Treatment End Difference (Week 132): At the end of the active 132-week treatment period, the between-group difference in eGFR change from baseline was 2.6 mL/min/1.73 m² (95% CI: 0.5 to 4.7).
• eGFR Slope: The difference in total eGFR slope (from baseline to week 136) was 1.4 mL/min/1.73 m² per year, demonstrating a clinically meaningful preservation of long-term kidney function.

Safety and Tolerability

The safety and tolerability profile of atrasentan was highly favorable and consistent with previous analyses. The active and placebo arms were well-balanced in treatment-emergent adverse events, with no new safety signals or unexpected toxicities observed.

"These results provide robust evidence of clinically meaningful slowing of kidney function decline over more than two years of treatment, reinforcing findings from the earlier analysis of proteinuria reduction. They highlight the role of a highly selective endothelin A receptor antagonist as part of an evolving treatment approach for IgAN." — Dr. Richard Lafayette, Stanford University Medical Center and ALIGN Study Investigator