Novartis atrasentan Phase III data show clinically meaningful proteinuria reduction further advancing company's IgA nephropathy (IgAN) portfolio
Novartis presented results from a pre-specified interim analysis of the Phase III ALIGN study of atrasentan, an investigational oral selective endothelin A (ETA) receptor antagonist, in patients with IgA nephropathy (IgAN).
Patients treated with atrasentan, in addition to supportive care (maximally tolerated and stable dose of a renin-angiotensin system [RAS] inhibitor), achieved a 36% (p<0.0001) reduction in proteinuria (as measured by 24-hour urine protein to creatinine ratio [UPCR]) at 36 weeks when compared to placebo on top of supportive care.
The results were presented during a late-breaking clinical trials session at the European Renal Association (ERA) Congress. The study also showed atrasentan has a favorable safety profile consistent with previously reported data.
Proteinuria reduction is a recognized surrogate marker correlating with delaying progression to kidney failure and has been used as an endpoint in IgAN clinical trials to support accelerated regulatory approvals. US FDA submission for atrasentan in IgAN is on track for the first half of 2024.
The ALIGN study continues in a blinded manner, and therefore only limited interim analysis results can be presented. The final analysis, including the key secondary endpoint of change from baseline in estimated glomerular filtration rate (eGFR) at 136 weeks, and the results in participants receiving a sodium-glucose co-transporter-2 (SGLT2) inhibitor as background care in an exploratory cohort, is expected in 2026.
Atrasentan is an investigational potent and selective oral ETA receptor antagonist, currently in Phase III development for IgAN and early-stage development for other rare kidney diseases. Activation of the ETA receptor contributes to elevated proteinuria, which is associated with kidney damage, fibrosis and loss of kidney function in IgAN. Atrasentan has potential to be added to current supportive therapy to reduce persistent proteinuria and preserve kidney function for a broad patient population. Preclinical models have also suggested that atrasentan may reduce inflammation and fibrosis in IgAN.
May 27, 2024
