Novartis’ Atrasentan Meets Primary Endpoint in Phase 3 Study for Treatment of IgAN

Rare Daily Staff

Novartis reported positive topline results from the interim analysis of the ongoing pivotal phase 3 ALIGN study of atrasentan in patients with IgA nephropathy.

The study met its primary efficacy endpoint at the 36-week interim analysis, with atrasentan demonstrating superiority versus placebo with a clinically meaningful and highly statistically significant reduction in proteinuria (protein in urine) in patients with IgAN receiving supportive care. In the study, the safety profile of atrasentan was consistent with previously reported data from the phase 2 AFFINITY study IgAN. Based on the results from this interim proteinuria endpoint analysis, Novartis plans to submit an application in 2024 for possible accelerated approval in the United States.

“These positive topline phase 3 data showcase the potential of atrasentan to improve outcomes for patients with IgAN by demonstrating clinically meaningful proteinuria reduction,” said Shreeram Aradhye, president of development and chief medical officer, Novartis. “Along with investigational iptacopan, which recently also showed positive topline phase 3 results, and investigational zigakibart, our development portfolio of three highly differentiated late-stage therapies in IgAN has the potential to provide much-needed treatment options for people living with this debilitating disease.”

IgAN is a progressive, rare kidney disease that mostly affects young adults. In IgAN, autoimmune reaction to an abnormal form of IgA results in formation of immune complexes that deposit in the kidney. These immune complexes trigger an inflammatory response leading to progressive kidney damage and loss of kidney function. Up to 30 percent of people who have IgAN with persistent higher levels of proteinuria (≥1 g/day) progress to kidney failure within 10 years. There is a need for effective therapies for IgAN that can help slow progression to kidney failure.

Atrasentan, an investigational oral endothelin A receptor antagonist in development for IgAN and other rare kidney diseases, was added to the Novartis portfolio through the recent acquisition of Chinook Therapeutics for $3.2 bilion.

The ALIGN study continues in a blinded manner to evaluate the change in kidney function over 136 weeks as measured by estimated glomerular filtration rate (eGFR), with topline results from the confirmatory endpoint analysis expected in the first quarter of 2026.

Photo: Shreeram Aradhye, president of development and chief medical officer, Novartis