Novartis Reports Final Data of ALIGN Trial in IgAN

Why It Matters

The results address a critical unmet need for disease‑modifying treatments in IgAN, offering clinicians a new option to preserve kidney function and potentially delay dialysis.

Key Takeaways

• Vanrafia reduced eGFR decline by 2.39 ml/min/1.73 m².
• 340 IgAN patients completed 132‑week double‑blind trial.
• Benefit persisted in patients on SGLT2 inhibitors.
• Primary endpoint measured proteinuria change at week 36.
• Novartis also developing iptacopan and zigakibart for IgAN.

Pulse Analysis

IgA nephropathy remains one of the leading causes of progressive chronic kidney disease, yet therapeutic options beyond renin‑angiotensin system (RAS) blockade are limited. Standard care now incorporates optimized RAS inhibitors and, increasingly, sodium‑glucose co‑transporter‑2 (SGLT2) inhibitors to curb proteinuria and slow eGFR loss. Against this backdrop, Novartis designed the ALIGN trial as a rigorous, global, double‑blind study to evaluate whether targeting endothelin‑A receptors with Vanrafia could add a novel mechanism of renal protection.

The final analysis revealed a statistically and clinically meaningful 2.39 ml/min/1.73 m² slower eGFR decline after 132 weeks of therapy, with an even larger 2.59 ml/min/1.73 m² benefit observed at week 132. Importantly, these gains were maintained in the subgroup receiving concurrent SGLT2 inhibition, suggesting additive effects without safety concerns. The trial also met its interim proteinuria endpoint, reinforcing the drug’s impact on both functional and surrogate markers of disease activity. Such data position Vanrafia as a viable adjunct to existing regimens, potentially reshaping treatment algorithms for high‑risk IgAN patients.

Beyond Vanrafia, Novartis is expanding its IgAN portfolio with iptacopan, a complement factor B inhibitor, and the investigational molecule zigakibart, reflecting a broader strategy to address multiple pathogenic pathways. If regulatory approvals follow, the combined pipeline could capture a sizable market segment, given the prevalence of IgAN and the high cost of dialysis. The ALIGN outcomes also set a benchmark for future phase‑III studies, encouraging the industry to explore combination therapies that integrate endothelin antagonism with RAS and SGLT2 blockade for maximal renal preservation.