Novartis’ Phase III ALIGN trial data show Vanrafia® (atrasentan) slows eGFR decline by 2.39 mL/min/1.73m² in IgAN patients, supporting full approval filings in 2026 after 2025 accelerated nod.
Written By: Samiksha Jadhav BPharm
Reviewed By: Pharmacally Editorial Team
Novartis announced final results from the Phase III ALIGN study, demonstrating that Vanrafia® (atrasentan) supports slowing the decline in kidney function among adults with IgA nephropathy (IgAN). According to Novartis, this endothelin receptor antagonist showed a clinically meaningful difference in estimated glomerular filtration rate (eGFR) compared to placebo.
As per Novartis ALIGN trial (NCT04573478) was a randomized, double-blind, placebo-controlled Phase III study involving 340 patients with biopsy-confirmed IgAN and proteinuria ≥1 g/day despite optimized renin-angiotensin system (RAS) inhibitor therapy.
Novartis reports that patients received once-daily oral Vanrafia 0.75 mg or placebo for about 132 weeks, alongside stable RAS inhibitors; a subgroup also used SGLT2 inhibitors.
Novartis states the primary endpoint from interim analysis was proteinuria reduction at week 36, previously met with a 36.1% decrease. According to Novartis, the key secondary endpoint for final analysis eGFR change from baseline to week 136 (4 weeks post-treatment) favored Vanrafia by 2.39 mL/min/1.73m² versus placebo (p=0.057).
Novartis further reports additional benefits at week 132 (2.59 mL/min/1.73m² difference, p=0.039) and across subgroups on SGLT2 inhibitors.
Ruchira Glaser, M.D., Global Head of Cardiovascular, Renal & Metabolic Development at Novartis stated “Progressive diseases like IgAN urgently need therapies targeting multiple drivers; Vanrafia integrates seamlessly into existing regimens with a consistent safety profile.”
According to Novartis, the safety data aligned with prior studies, reinforcing Vanrafia’s potential as a foundational IgAN therapy alongside Novartis’ portfolio including Fabhalta® (iptacopan) and investigational zigakibart. Clinicians should monitor liver enzymes before and during Vanrafia due to potential hepatotoxicity risks with endothelin antagonists; Vanrafia also carries warnings for serious birth defects.
Vanrafia (atrasentan) is a potent, highly selective endothelin A (ETA) receptor antagonist targeting the endothelin system, a key driver in IgAN progression. It is the first and only selective ETA antagonist approved for primary IgAN a once-daily oral therapy that integrates seamlessly with existing supportive care (e.g., RAS inhibitors with or without SGLT2 inhibitors) without titration or a REMS program.
Vanrafia gained accelerated approval in the US and China in 2025 for reducing proteinuria in IgAN adults. Novartis plans 2026 submissions for traditional (full) approvals based on these Phase III findings, despite not fully meeting the primary eGFR statistical threshold.
IgAN, a leading glomerular disease, drives 40% of end-stage kidney disease cases globally, highlighting the need for disease-modifying options.
References
Novartis Vanrafia® Phase III data support slowing of kidney function decline in patients with IgA nephropathy, 13 February 2026, Novartis Vanrafia® Phase III data support slowing of kidney function decline in patients with IgA nephropathy | Novartis
Atrasentan in Patients with IgA Nephropathy (ALIGN), ClinicalTrials.gov ID NCT04573478, Study Details | NCT04573478 | Atrasentan in Patients with IgA Nephropathy | ClinicalTrials.gov