The U.S. Food and Drug Administration (FDA) granted traditional approval to Novartis's iptacopan (Fabhalta) to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) at risk of disease progression. The decision marks a significant regulatory milestone for a condition that often leads to kidney failure and for which few disease-modifying therapies have been available.

The approval converted iptacopan from its earlier accelerated approval status to traditional approval, based on results from the APPLAUSE-IgAN phase III clinical trial. That study showed that iptacopan reduced the rate of estimated glomerular filtration rate (eGFR) decline by 48% compared with placebo over a 24-month period. Patients receiving iptacopan had an annualized mean change in eGFR of -3 mL/min/1.73 m² per year, while those on placebo experienced a decline of -5.7 mL/min/1.73 m² per year. The treatment effect was consistent across all prespecified subgroups analyzed in the trial.

The safety profile of iptacopan remained consistent with previously reported data from earlier studies. The most commonly reported adverse events included abdominal pain, dizziness, and nausea. The drug carries a boxed warning for an increased risk of infections caused by encapsulated bacteria, a known concern with complement pathway inhibitors. To mitigate this risk, iptacopan is available only through a risk evaluation and mitigation strategy (REMS) program that requires patients to be appropriately vaccinated before initiating treatment.

Iptacopan is a Factor B inhibitor designed to selectively target the alternative complement pathway, which plays a central role in the immune-mediated kidney damage seen in IgAN. Patients with IgAN develop kidney injury due to an abnormal accumulation of immunoglobulin A (IgA) antibodies in the glomeruli, triggering inflammation and progressive loss of function. The disease is typically diagnosed in young adulthood and affects an estimated 2.5 per 100,000 adults worldwide each year. Without effective intervention, approximately half of IgAN patients progress to kidney failure or death within 10 to 20 years of diagnosis.

With this approval, iptacopan becomes the third therapy for IgAN to receive traditional FDA approval. The other two are budesonide (Tarpeyo) and sparsentan (Filspari). In contrast, atrasentan (Vanrafia), sibeprenlimab (Voyxact), and atacicept (Trutakna) have received only accelerated FDA approvals for IgAN, based on their ability to reduce proteinuria—a surrogate marker—rather than direct evidence of slowing kidney function decline. Traditional approval requires demonstration of clinical benefit on a direct measure of organ function, such as eGFR trajectory.

Dana Rizk, MD, an investigator at the University of Alabama at Birmingham who participated in the clinical development of iptacopan, emphasized the clinical significance of the findings. "The ability to significantly slow kidney function decline is a critical treatment goal," Rizk said. She added, "This approval of Fabhalta reinforces the importance of targeting underlying disease mechanisms, including complement activation, in treating IgAN to help preserve kidney health."

IgA nephropathy is a chronic, progressive kidney disease with limited therapeutic options. Most patients are diagnosed during young adulthood, and the condition carries a high long-term risk of kidney failure. Historically, treatment has relied on blood pressure control and immunosuppression, which do not address the specific immune pathways driving the disease. Iptacopan’s mechanism—targeting the alternative complement pathway via Factor B inhibition—represents a precision medicine approach aligned with emerging understanding of IgAN pathophysiology.

The APPLAUSE-IgAN trial provides the first phase III evidence that directly slowing eGFR decline is achievable in this population through complement inhibition. Given that eGFR loss is a direct predictor of kidney failure, this outcome offers a clinically meaningful benefit. The FDA’s conversion to traditional approval validates the strength of this evidence and may influence treatment guidelines, insurance coverage, and clinical adoption. Novartis, a Swiss-American multinational pharmaceutical corporation, now markets iptacopan for three rare kidney and blood disorders: IgAN, paroxysmal nocturnal hemoglobinuria, and complement 3 glomerulopathy.