From Proteinuria to Kidney Function: Fabhalta Receives Full FDA Approval for IgA Nephropathy

The treatment goal for IgA nephropathy is ultimately not merely to reduce the amount of protein in the urine, but to delay the continued loss of kidney function as much as possible. The U.S. Food and Drug Administration (FDA) has converted the accelerated approval of Novartis’s oral drug Fabhalta (iptacopan) for this disease into full approval for adults with primary IgA nephropathy who are at risk of disease progression. The focus of the approval has also advanced from the previous reduction of proteinuria to slowing kidney function decline.

The decision is based on two-year data from the placebo-controlled Phase 3 APPLAUSE-IgAN trial. According to the FDA’s updated label, the estimated glomerular filtration rate (eGFR) declined by an annual average of 3.0 mL/min/1.73 m² in patients receiving iptacopan, compared with 5.7 mL/min/1.73 m² in the placebo group. Novartis described the difference between the groups as a 48% relative slowing in the rate of kidney function decline, providing longer-term kidney function outcomes that support the earlier efficacy signal based on proteinuria.

Another renal composite endpoint showed a difference in the same direction: events occurred in 21.4% of patients in the Fabhalta group and 33.5% of those in the placebo group, with a risk ratio of 0.6. These data indicate that the treatment benefit is not reflected only in a laboratory surrogate endpoint; however, how long kidney failure can be delayed in individual patients and which populations benefit most still require longer-term follow-up and real-world data to answer.

Iptacopan is a complement factor B inhibitor that intervenes in the glomerular inflammation and damage triggered by IgA immune complexes by inhibiting the alternative complement pathway. It first received accelerated approval in 2024 based on a reduction in proteinuria, when the FDA accepted an earlier surrogate-endpoint analysis from the same trial. Completion of the 24-month kidney function verification has now provided the evidence of clinical benefit required under the accelerated approval pathway.

Beyond efficacy, the infection risks associated with complement inhibition cannot be minimized. The Fabhalta label carries a boxed warning that patients may develop serious infections caused by encapsulated bacteria. Relevant vaccinations must be completed as required before treatment, and prescribing and use are also subject to the Fabhalta Risk Evaluation and Mitigation Strategy (REMS). Vaccination does not eliminate all risk, and patients must remain alert for symptoms of infection and receive appropriate monitoring during treatment.

This conversion to full approval adds an oral immune-pathway therapy supported by two years of kidney function evidence for IgA nephropathy and also raises the comparative standard for subsequent drug development. However, APPLAUSE-IgAN compared Fabhalta with placebo and did not directly demonstrate that Fabhalta is superior to other existing or emerging treatments. How to balance efficacy, safety, ease of administration, and long-term kidney outcomes must still be determined according to the patient’s risk and the clinical context.