Novartis receives FDA accelerated approval for Fabhalta (iptacopan), the first and only complement inhibitor for the reduction of proteinuria in primary IgA nephropathy (IgAN)

Ad hoc announcement pursuant to Art. 53 LR

• Fabhalta achieved a 44% proteinuria reduction from baseline in Phase III APPLAUSE-IgAN interim analysis, compared with 9% in placebo arm, demonstrating a clinically meaningful reduction of 38% vs. placebo (p<0.0001)¹
  
• Fabhalta is an inhibitor of the alternative complement pathway, activation of which is thought to contribute to the pathogenesis of IgAN^1-4
  
• Despite current standard of care, up to 50% of IgAN patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis^5-11
  
• This marks the first approval from Novartis’ renal pipeline, which also includes atrasentan and zigakibart
  

Basel, August 8, 2024 – Novartis today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Fabhalta (iptacopan), a first-in-class complement inhibitor for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. This is generally defined as a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g¹. Fabhalta specifically targets the alternative complement pathway of the immune system. When overly activated in the kidneys, the complement system is thought to contribute to the pathogenesis of IgAN^1-4.

This indication is granted under accelerated approval based on the pre-specified interim analysis of the Phase III APPLAUSE-IgAN study measuring reduction in proteinuria at 9 months compared to placebo. It has not been established whether Fabhalta slows kidney function decline in patients with IgAN. The continued approval of Fabhalta may be contingent upon verification and description of clinical benefit from the ongoing Phase III APPLAUSE-IgAN study, evaluating whether Fabhalta slows disease progression as measured by estimated glomerular filtration rate (eGFR) decline over 24 months¹. The eGFR data are expected at study completion in 2025 and are intended to support traditional FDA approval.

“The heterogeneous and progressive nature of IgA nephropathy has made it challenging to effectively treat this disease. Thankfully, the treatment landscape is rapidly evolving,” said Professor Dana Rizk, Investigator and APPLAUSE-IgAN Steering Committee Member and professor in the University of Alabama at Birmingham Division of Nephrology. “Mounting clinical evidence underscores the pivotal role of complement activation in IgA nephropathy. I am thrilled that this advancement is now available to help enable a targeted treatment approach for IgAN patients.”