Novartis receives FDA accelerated approval for Fabhalta

Novartis announced that the FDA has granted accelerated approval for Fabhalta, a first-in-class complement inhibitor for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy at risk of rapid disease progression. This is generally defined as a urine protein-to-creatinine ratio greater than or equal to1.5 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. 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 decline over 24 months1. The eGFR data are expected at study completion in 2025 and are intended to support traditional FDA approval. 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. These patients often require maintenance dialysis and/or kidney transplantation5-11. Effective, targeted therapies with different mechanisms of action can help physicians select the most appropriate treatment for patients. The ongoing Phase III APPLAUSE-IgAN study is evaluating the efficacy and safety of twice-daily oral Fabhalta (200 mg) versus placebo in adult IgAN patients on a stable dose of maximally-tolerated renin-angiotensin system (RAS) inhibitor therapy with or without a stable dose of SGLT2i. The primary endpoint for the interim analysis was the percent reduction of proteinuria, a marker of kidney damage, measured by comparing UPCR at 9 months to baseline. Fabhalta achieved a 44% reduction in proteinuria at 9 months relative to baseline, compared with a 9% reduction in the placebo arm, demonstrating a clinically meaningful and statistically significant 38% reduction vs. placebo (pless than0.0001). The treatment effect on UPCR at 9 months was consistent across all subgroups, including age, sex, race and baseline disease characteristics (such as baseline eGFR and proteinuria levels), and the use of SGLT2i1. Fabhalta demonstrated a favorable safety profile, consistent with previously reported data. In patients with IgAN, the most common adverse reactions (greater than or equal to5%) with Fabhalta were upper respiratory tract infection, lipid disorder, and abdominal pain. Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy that requires specific vaccinations.