Novartis’s Fabhalta FDA approval IgAN decision, announced this week, converts the drug’s original accelerated clearance into a traditional approval for slowing kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) at risk of disease progression. The US FDA approved the expanded label for Fabhalta (iptacopan) under priority review, making it the first complement inhibitor to receive full approval for this endpoint in IgAN. The decision follows the drug’s initial accelerated approval in August 2024, which had permitted marketing based on proteinuria reduction alone, an intermediate biomarker rather than a direct measure of kidney function.
Iptacopan is an oral, small-molecule inhibitor of complement Factor B, a component of the alternative complement pathway implicated in glomerular inflammation and iptacopan kidney disease pathology. By blocking Factor B, the drug limits formation of the C3 convertase and downstream generation of inflammatory mediators associated with IgA nephropathy. Because of an elevated risk of infections from encapsulated bacteria, Fabhalta remains available only through a Risk Evaluation and Mitigation Strategy program that requires vaccination before treatment begins.
The approval rested on the Phase III APPLAUSE-IgAN trial, which enrolled adults with biopsy-confirmed primary IgAN and compared iptacopan against placebo added to background supportive care. The primary endpoint was annualized change in estimated glomerular filtration rate (eGFR) over two years. Patients receiving Fabhalta lost an annualized 3.0 mL/min/1.73m², compared with 5.7 mL/min/1.73m² for placebo, a difference Novartis said represented a statistically significant and clinically meaningful slowing of decline, as previously reported. The company said the safety profile was consistent with data supporting the drug’s earlier approvals, with abdominal pain, dizziness, and nausea the most commonly reported adverse events.