Novartis Fabhalta wins FDA traditional approval in IgA nephropathy

Novartis has secured traditional FDA approval for Fabhalta (iptacopan) to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) at risk of disease progression. The approval converts an accelerated approval granted in August 2024, which had been limited to the reduction of proteinuria. The new label reflects a more clinically meaningful endpoint: preservation of kidney function over time.

The decision was based on Phase III data from the APPLAUSE-IgAN study, in which iptacopan showed an annualised mean change from baseline in estimated glomerular filtration rate (eGFR) of -3.0 mL/min/1.73 m² per year, compared with -5.7 mL/min/1.73 m² per year in the placebo arm. That translates to a 48% reduction in the rate of eGFR decline. Clinically meaningful reductions in proteinuria were observed as early as two weeks and were sustained across the treatment period. The safety profile was consistent with prior data; the most common adverse events were abdominal pain, dizziness and nausea. Because iptacopan inhibits the alternative complement pathway and may raise the risk of serious infections caused by encapsulated bacteria, it remains available only through a Risk Evaluation and Mitigation Strategy programme requiring appropriate vaccination before treatment begins.

Dana Rizk, Professor of Medicine in the Division of Nephrology at the University of Alabama at Birmingham and a steering committee member for APPLAUSE-IgAN, said: "The ability to significantly slow kidney function decline is a critical treatment goal. This approval of Fabhalta reinforces the importance of targeting underlying disease mechanisms, including complement activation, in treating IgAN to help preserve kidney health."

Disease burden and market context

IgAN is one of the most common autoimmune kidney diseases globally, with roughly 25 new diagnoses per million people each year. The prognosis for a substantial subset of patients is poor: up to half of those with persistent proteinuria progress to kidney failure within 10 to 20 years, typically requiring dialysis or transplantation. Until recently, treatment options were largely limited to supportive care, blood pressure management, and broad immunosuppression with a modest evidence base.

The approval adds a confirmed mechanistic option to a landscape that has grown considerably more competitive over the past two years. Iptacopan targets the alternative complement pathway via Factor B inhibition, a mechanism distinct from the endothelin receptor antagonism used by atrasentan, which Novartis also markets under the brand name Vanrafia for IgAN. The company is additionally developing zigakibart, an investigational anti-APRIL antibody, for the same indication, giving it one of the broader IgAN-specific portfolios among large-cap pharmaceutical companies.

Competitive positioning and regulatory read-across

Beyond Novartis, the IgAN space now features approved or late-stage agents with distinct targets: sparsentan, which combines endothelin and angiotensin receptor blockade, and several APRIL or BAFF pathway inhibitors in clinical development across other sponsors. The KDIGO 2025 clinical practice guideline, published earlier this year, explicitly supports the use of complement pathway inhibitors in eligible patients, providing a degree of prescriber guidance that was absent when iptacopan first entered the market under accelerated approval. That guideline endorsement, combined with the conversion to traditional approval, is likely to support formulary access discussions with US payers. Novartis says nearly all US patients currently pay $10 or less per month through its support programmes.