Novartis Vanrafia Phase III Data Show Slowing of Kidney Function Decline in IgA Nephropathy

Novartis announced final results from the Phase III ALIGN study on February 13, 2026, showing that Vanrafia (atrasentan) slowed kidney function decline in adults with IgA nephropathy (IgAN). Vanrafia showed a difference of 2.39 ml/min/1.73m² in estimated glomerular filtration rate (eGFR) change from baseline versus placebo (2-sided p = 0.057) at Week 136, four weeks after the end of study treatment.

Clinically meaningful results were observed with Vanrafia compared to placebo in eGFR change from baseline at the end of study treatment at Week 132, and in the prespecified exploratory group of patients additionally receiving sodium-glucose co-transporter-2 (SGLT2) inhibitors. At the end of treatment at Week 132, the eGFR change from baseline compared to placebo was 2.59 ml/min/1.73 m² (nominal 2-sided p = 0.039).

The ALIGN study is a global, randomized, multicenter, double-blind, placebo-controlled trial evaluating the efficacy and safety of Vanrafia versus placebo in patients with IgA nephropathy at risk of progressive kidney function decline. The study evaluated 340 patients and provides the longest follow-up period in pivotal Phase III studies for IgAN. Safety was consistent with previous findings. The most common adverse reactions reported with atrasentan in clinical trials were peripheral edema and anemia.

Vanrafia received accelerated approval in the United States and China in April 2025 for the reduction of proteinuria in adults with IgAN. In April 2025, it had not been established whether Vanrafia slows kidney function decline in patients with IgAN. The continued approval of Vanrafia was contingent upon verifying clinical benefit from the ongoing Phase III ALIGN study evaluating whether Vanrafia slows disease progression as measured by eGFR decline at week 136. Following the positive trial results, Novartis plans to submit for traditional approval in 2026.

IgA nephropathy is a progressive autoimmune kidney disease with approximately 25 per million people newly diagnosed worldwide each year. IgAN is caused by the buildup of immunoglobulin A (IgA) protein in the glomeruli, causing inflammation and reducing the kidneys' ability to filter waste. The condition leads to glomerular inflammation (when the small filters in the kidneys are inflamed), proteinuria (excess protein in urine), and a gradual decline in eGFR. Up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis, often requiring dialysis or kidney transplantation as part of long-term disease management.

People living with IgAN often face mental, social, and economic challenges. Supportive care has not addressed the underlying causes of the disease and often fails to slow disease progression, reinforcing the need for more targeted therapies for IgAN.

Vanrafia (atrasentan) is a potent and highly selective endothelin A (ETA) receptor antagonist, which is part of the endothelin system, a key system involved in the progression of IgAN. Vanrafia is the first and only selective ETA receptor antagonist approved for primary IgAN, a once-daily, oral treatment that can be seamlessly added to, or used alongside, existing supportive care (e.g. renin-angiotensin system (RAS) inhibitor with or without SGLT2 inhibitor) without the need for titration. Vanrafia does not require a Risk Evaluation and Mitigation Strategy (REMS) program.

Novartis gained Vanrafia as part of its $2.5 billion acquisition of biopharma Chinook Therapeutics in June 2023. Alongside Vanrafia, Novartis continues to advance its multi-asset IgAN portfolio, which also includes Fabhalta (iptacopan) and investigational compound zigakibart.

Fabhalta is an oral, Factor B inhibitor of the alternative complement pathway. Fabhalta is approved in the United States and the EU for treating adults with paroxysmal nocturnal hemoglobinuria. The therapy also received accelerated approval in the United States in August 2024 and China in September 2025 to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression. In 2025, Fabhalta further gained approvals in the United States, European Union, China and Japan for the treatment of adults with C3 glomerulopathy, becoming the first approved therapy for this condition. Fabhalta generated sales of $155 million in the fourth quarter and $505 million in 2025.

Zigakibart is an anti-APRIL monoclonal antibody for IgAN that was also included in the acquisition of Chinook. Zigakibart has shown potential as a more tolerable treatment to broader-acting lymphocyte-depleting therapies and is currently in phase III clinical trials.