October 30, 2023
Novartis' Atrasentan Shows Promise in Phase 3 Study for IgA Nephropathy Treatment
Novartis reported encouraging results from the Phase 3 ALIGN study, illustrating the effectiveness of atrasentan in patients diagnosed with IgA nephropathy (IgAN). Atrasentan demonstrated a significant decrease in proteinuria compared to the placebo during the 32-week interim analysis.
Atrasentan functions as an oral endothelin A receptor antagonist (ERA) specifically designed for IgA nephropathy. Novartis aims to pursue accelerated approval for atrasentan by 2024, with the final outcome of the trial is anticipated in 2026.
IgA nephropathy stands as a significant contributor to chronic kidney disease and subsequent kidney failure. About 30% of individuals affected by IgA nephropathy progress to kidney failure.
Atrasentan is an oral endothelin A receptor, a crucial component in Novartis' product range, which became part of their portfolio following the acquisition of Chinook Therapeutics. Additionally, there is ongoing development of zigakibart, a subcutaneous form of the drug, developed for IgA nephropathy.
October 02, 2023
Novartis's iptacopan met the primary endpoint of proteinuria reduction in patients with IgA nephropathy.
Novartis has announced that iptacopan met the primary endpoint in patients with IgA nephropathy (IgAN), a kidney disease with significant clinical impact. The Phase III trial, APPLAUSE-IgAN (NCT04578834), achieved its pre-determined interim analysis primary endpoint, demonstrating that iptacopan outperformed a placebo in reducing proteinuria in patients with IgAN. Iptacopan is a novel oral factor B inhibitor that targets the complement system's alternative pathway, a vital aspect of IgAN pathogenesis.
IgAN is a kidney disease primarily affecting young adults, leading to chronic kidney disease and kidney failure worldwide. Novartis is now planning to share these interim results with the FDA to secure accelerated approval for iptacopan potentially. The study will continue, with the final data set to be collected over 24 months, with results expected in 2025.
IgAN presents a significant health challenge, affecting approximately 25 people per million annually, with up to 30% of those with persistently high proteinuria at risk of kidney failure within a decade. Current treatment approaches offer some support, but they need to address a crucial aspect of IgAN progression - the activation of the complement system.
Iptacopan, developed by Novartis, seeks to tackle this issue by inhibiting factor B, an essential protease in the alternative complement pathway. Following positive Phase III results for paroxysmal nocturnal hemoglobinuria (PNH), the drug is already under regulatory review. Moreover, iptacopan is undergoing Phase III investigations for other complement-mediated diseases, including C3 glomerulopathy, atypical hemolytic uremic syndrome, and immune complex membranoproliferative glomerulonephritis.
The APPLAUSE-IgAN study is a Phase III trial involving 470 adult primary IgAN patients. It employs a double-blind, placebo-controlled design to assess the safety and efficacy of iptacopan, administered orally twice daily at a 200mg dose. The study's primary endpoints, for both interim and final analyses, are the reduction of proteinuria at nine months (measured using the urine protein to creatinine ratio or UPCR) and the annualized total estimated glomerular filtration rate (eGFR) slope over 24 months. These results offer hope for a potential breakthrough in the treatment of IgAN and provide optimism for patients suffering from this debilitating kidney disease.
Novartis has recently expanded its renal portfolio by acquiring Chinook Therapeutics, further strengthening its commitment to addressing IgAN.