It’s déjà vu all over again. Just as the kidney disease space becomes increasingly competitive, Novartis has found itself intending to turn a statistical miss into a regulatory win.
Despite the phase 3 Align trial narrowly failing to hit its kidney function endpoint, Novartis announced Friday that it will pursue traditional FDA approval for Vanrafia (atrasentan) in IgA nephropathy (IgAN).
The Swiss pharma wouldn’t be the first to try to convince the FDA of a full IgAN nod following a phase 3 kidney function miss. Travere’s Protect phase 3 trial had previously failed to show a statistically significant advantage for Filspari on kidney function as measured by the estimated glomerular filtration rate (eGFR) after two years. But the FDA still converted Filspari’s accelerated approval in IgAN into a full nod in 2024.
For its part, Novartis is leaning on a “positive difference” with Vanrafia versus placebo in eGFR change from baseline at Week 136, as well as a “clinically meaningful” improvement for the drug at Week 132, when study treatment ended.
The difference at Week 136, a key secondary endpoint of the Align trial, arrived at 2.39ml/min/1.73m2, with a p-value of 0.057 that missed statistical significance. At Week 132, the difference in eGFR change was 2.59ml/min/1.73m2, with a nominal p-value of 0.039, Novartis said Friday.
“Progressive and complex diseases such as IgAN present an urgent need for medicines that can target the different drivers of the disease. Vanrafia can be seamlessly integrated into patients’ existing treatment plans, with a consistent safety profile,” Ruchira Glaser, M.D., Novartis’ global head of cardiovascular, renal and metabolic development, said in a Feb. 13 statement. “We are pleased with today’s phase 3 Align results, which add to the growing evidence of Vanrafia as a potential foundational therapy to slow kidney function decline.”
Vanrafia gained its FDA accelerated approval in April 2025. As part of Novartis’ 2023 acquisition of Chinook Therapeutics, Vanrafia was Novartis’ second IgAN drug to cross the FDA finish line. The selective endothelin A receptor antagonist (ERA) does not come with the burden of an FDA-mandated REMS safety program, which sets it apart from Filspari.
Besides Vanrafia, Novartis has Fabhalta, a complement inhibitor that showed statistically significant superiority compared with placebo in slowing IgAN progression measured by eGFR changes over two years. Novartis announced the positive final analysis from the phase 3 Applause-IgAN study in October and plans regulatory submissions this year.
Originally approved by the FDA in December 2023 for the treatment of paroxysmal nocturnal hemoglobinuria, Fabhalta added an accelerated approval in IgAN in 2024 and then became the first FDA-approved therapy for C3 glomerulopathy in March 2025. The drug nearly tripled sales last year to $505 million, and Novartis has put its peak sales potential across multiple indications at above $3 billion.
IgAN is a progressive autoimmune kidney disease that sees about 25 million new diagnoses each year worldwide, according to Novartis.
To tackle the disease from a third angle, Novartis is testing its anti-APRIL antibody zigakibart in the phase 3 Beyond trial. The company recently amended the study’s protocol to focus on eGFR to potentially directly support a full approval. An interim eGFR readout is expected in the first half of 2027.