FDA Approves Novartis' Fabhalta for IgAN; Vanrafia Data Show Slower Kidney Decline
FDA approved Novartis' Fabhalta for IgAN to slow kidney function decline. Phase III ALIGN data for Vanrafia showed ~34% slower eGFR decline vs placebo and were published in The Lancet.
US FDA grants traditional approval for Novartis' Fabhalta to slow kidney function decline in primary IgAN. Fabhalta (iptacopan), a first-in-class complement inhibitor, received approval under a priority review designation after an initial FDA accelerated approval in August 2024 for the reduction of proteinuria in primary IgAN.
The approval was based on data from the phase III APPLAUSE-IgAN study. Results demonstrated statistically significant and clinically meaningful improvement in estimated glomerular filtration rate (eGFR) over two years, with Fabhalta showing an annualized mean change from baseline in eGFR of -3.0 mL/min/1.73 m2/yr compared with -5.7 mL/min/1.73 m2/yr for placebo. Fabhalta consistently outperformed placebo across key kidney outcomes. The most common adverse events with Fabhalta in patients with IgAN were abdominal pain, dizziness and nausea. Fabhalta may increase the risk of serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) program requiring appropriate vaccinations prior to treatment.
Each year, approximately 25 people per million worldwide are newly diagnosed with IgAN, one of the most common autoimmune kidney diseases. Up to 50 per cent of IgAN patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis, often requiring dialysis and/or kidney transplantation.
In related kidney disease news, Novartis reported final 2.5-year Phase III ALIGN results showing slower kidney function decline with Vanrafia (atrasentan) versus placebo in adults with IgAN. Results were published in The Lancet and presented at the European Renal Association (ERA) Congress. The annualized total eGFR slope was -2.7 mL/min/1.73 m2/year with Vanrafia versus -4.1 with placebo, representing a ~34% slower decline (p=0.003). Vanrafia reduced urine protein-to-creatinine ratio by 38.3% relative to placebo at 9 months, with reductions sustained through end of treatment. In a cohort of patients additionally receiving SGLT2 inhibitors, change from baseline in eGFR at end of study was -1.5 with Vanrafia versus -10.6 with placebo (p=0.004). Safety was consistent with prior studies, with adverse events similar to placebo and no new signals observed.
Vanrafia received accelerated approval in the U.S. and China for reduction of proteinuria in adults with IgAN in 2025. Novartis intends to use the ALIGN data to support submission for traditional approval in 2026. The ALIGN study randomized 340 patients with biopsy-proven IgAN to once-daily oral Vanrafia (0.75 mg) or placebo for approximately 132 weeks, with an additional cohort of 64 patients receiving an SGLT2 inhibitor.
Novartis is supporting the IgAN community through a growing portfolio that includes Fabhalta, Vanrafia and the investigational compound zigakibart. Nearly 100 percent of US patients pay $10 or less per month for Fabhalta.