Novartis bolsters the case for Vanrafia’s full approvals in IgA nephropathy

Novartis has released late-stage data for Vanrafia (atrasentan) that show the endothelin A (ETA) receptor antagonist could slow kidney function decline in adults with IgA nephropathy (IgAN).

The drug became the first of its kind to be approved for primary IgAN through accelerated approvals in the US and China and Novartis plans to file it for traditional approvals later this year.

The pharma company’s ALIGN phase III trial of the oral ETA receptor evaluated 340 patients and has the longest follow-up in pivotal phase III studies for IgAN.

It found Vanrafia enabled a clinically meaningful change in estimated glomerular filtration rate (eGFR) of 2.59 ml/min/1.73 m²at the study’s end, Week 132. These changes were also observed in patients who additionally received sodium-glucose co-transporter-2 (SGLT2) inhibitors.

Comparatively, at four weeks post-treatment in Week 136, this difference was 2.39 ml/min/1.73m² from baseline versus placebo.

Dr Ruchira Glaser, Global Head, Cardiovascular, Renal & Metabolic Development Unit, Novartis, said: “Progressive and complex diseases such as IgAN present an urgent need for medicines that can target the different drivers of the disease.

“We are pleased with today’s phase III ALIGN results, which add to the growing evidence of Vanrafia as a potential foundational therapy to slow kidney function decline.”
Novartis gained Vanrafia as part of its £2.5 billion acquisition of biopharma Chinook Therapeutics in June 2023 and the drug was subsequently approved by the US Food and Drug Administration (FDA) as once-daily treatment for the autoimmune kidney disease last April.

This new data from Novartis bolsters its ambitions for Vanrafia, which is one element of its renal/IgAN ambitions. The pharmaceutical company is also continuing to advance its Factor B inhibitor Fabhalta (iptacopan), which won its first US and Europe approvals in December 2023 and May 2024 respectively. Clinical findings announced in April 2024, showed its potential as the first IgAN treatment to specifically target the alternative complement pathway, Investigator Professor Dana Rizk shared at the time.

Novartis’ pipeline also includes zigakibart, an anti-APRIL monoclonal antibody (mAb) for IgAN that was also included in its 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.