The US Food and Drug Administration (FDA) has granted traditional approval to Novartis’ iptacopan (Fabhalta) to slow kidney function decline in adults with primary IgA nephropathy (IgAN) at risk of disease progression. The decision converts the therapy’s accelerated approval into a full approval supported by confirmatory phase 3 data from the APPLAUSE-IgAN trial.

The approval follows Priority Review and is supported by 2-year results from APPLAUSE-IgAN demonstrating that iptacopan significantly slowed kidney function decline compared with placebo while maintaining clinically meaningful reductions in proteinuria. According to Novartis, iptacopan is the first and only complement inhibitor approved to significantly slow kidney function decline in adults with primary IgAN.

“IgAN is a chronic, immune-mediated disease leading to kidney failure that can have a severe impact on patients’ lives,” Dana Rizk, MD, professor of medicine in the Division of Nephrology at the University of Alabama at Birmingham and a member of the APPLAUSE-IgAN Steering Committee, said in a statement. “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.”

APPLAUSE-IgAN Confirms Kidney Function Benefit With Iptacopan

Traditional approval was granted after confirmatory data demonstrated that early reductions in proteinuria observed with iptacopan translated into preservation of kidney function, a clinically meaningful outcome associated with delaying progression to kidney failure.

Earlier this year, Novartis announced that APPLAUSE-IgAN met its primary endpoint, supporting the supplemental regulatory submission that led to full approval.

The phase 3 trial showed patients treated with iptacopan experienced an annualized mean estimated glomerular filtration rate (eGFR) decline of -3.0 mL/min/1.73 m² per year compared with -5.7 mL/min/1.73 m² per year among those receiving placebo, representing a 48% slowing of kidney function decline.

Investigators also observed clinically meaningful reductions in proteinuria as early as 2 weeks after treatment initiation, with benefits sustained throughout the treatment period.

Iptacopan Targets Alternative Complement Pathway Activation in IgAN

Iptacopan is an oral factor B inhibitor that selectively targets the alternative complement pathway, a key driver of inflammation and kidney injury in IgAN. By inhibiting factor B, the therapy is designed to reduce complement-mediated damage and slow disease progression rather than solely addressing downstream manifestations of the disease.

The safety profile observed in APPLAUSE-IgAN was consistent with previously reported findings. The most common adverse events among patients with IgAN included abdominal pain, dizziness, and nausea.

Because complement inhibition increases the risk of serious infections caused by encapsulated bacteria, iptacopan remains available through a Risk Evaluation and Mitigation Strategy (REMS) program. Appropriate vaccinations are required before treatment initiation.

Approval Adds to Rapidly Expanding IgAN Treatment Landscape

Each year, approximately 25 people per million worldwide are diagnosed with IgAN, one of the most common autoimmune kidney diseases. Despite optimized supportive care, up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis, often requiring dialysis or kidney transplantation.

“Today’s approval reinforces Fabhalta’s role in preserving kidney function by significantly slowing disease progression, an outcome that matters deeply to patients at risk of long-term kidney damage,” Victor Bultó, president of Novartis US, said in a statement. “This milestone underscores the importance of continued innovation for people living with IgAN and our commitment to addressing the underlying drivers of disease.”

The approval further expands a rapidly evolving IgAN treatment landscape, where multiple targeted therapies have reached the clinic in recent years. Beyond complement inhibition with iptacopan, available and emerging approaches target endothelin signaling, APRIL, and B-cell biology, reflecting a broader shift toward mechanism-based therapies designed to slow disease progression and preserve kidney function.

References

1. Novartis Fabhalta® (iptacopan) receives FDA traditional approval as first and only complement inhibitor to significantly slow kidney function decline in primary IgAN. (2026, July 17). Novartis. https://www.novartis.com/news/media-releases/novartis-fabhalta-iptacopan-receives-fda-traditional-approval-first-and-only-complement-inhibitor-significantly-slow-kidney-function-decline-primary-igan

2. Perkovic V, Barratt J, Rovin B, et al. Alternative complement pathway inhibition with iptacopan in IgA nephropathy. N Engl J Med. 2025;392:531–543. doi:10.1056/NEJMoa2410316