A new medication called Fabhalta has demonstrated a significant ability to slow the progression of IgA nephropathy (IgAN), a serious autoimmune kidney disease, by slowing kidney function decline by 49.3% compared to placebo. The two-year results from the Phase III APPLAUSE-IgAN study, published in the New England Journal of Medicine, show that the drug reduced the likelihood of progression to kidney failure by 43% and helped 40.7% of patients achieve sustained reduction of protein in urine, offering hope to the millions living with this progressive condition .

What Is IgA Nephropathy and Why Does It Matter?

IgA nephropathy is a progressive autoimmune kidney disease that affects approximately 25 people per million worldwide each year. The condition causes inflammation in the small filters of the kidneys, leading to excess protein in urine and a gradual decline in kidney function measured by a marker called estimated glomerular filtration rate (eGFR). Without effective treatment, up to 50% of patients with persistent protein in their urine progress to kidney failure within 10 to 20 years of diagnosis, often requiring dialysis or kidney transplantation .

The disease is particularly challenging because supportive care alone has not addressed the underlying causes of the condition. Patients often face not only physical complications but also significant mental and social challenges as their kidney function declines. This is why the discovery of a medication that can slow disease progression represents a meaningful shift in how doctors approach IgAN treatment.

How Does Fabhalta Work to Protect Kidney Function?

Fabhalta (iptacopan) is an oral medication that works by targeting a specific pathway in the immune system called the alternative complement pathway. By inhibiting a protein called Factor B, Fabhalta reduces ongoing inflammation and kidney damage caused by the immune system attacking the kidney's filtering units. This targeted approach addresses one of the key drivers of kidney damage in IgAN, rather than simply managing symptoms .

The drug's mechanism represents a shift toward precision medicine in kidney disease treatment. Instead of relying on general anti-inflammatory approaches, Fabhalta specifically blocks the complement pathway that is overactive in IgAN patients. This selectivity may explain why the drug was able to achieve such substantial benefits in slowing kidney function decline.

What Did the Two-Year Study Show?

The APPLAUSE-IgAN study followed adults with biopsy-confirmed IgAN and persistent protein in their urine despite receiving optimized supportive care. Participants were randomly assigned to receive either Fabhalta or placebo and were monitored for up to 24 months. The results were striking across multiple measures of kidney health:

• Kidney Function Decline: Patients on Fabhalta experienced a decline in kidney function of 3.10 mL/min/1.73 m² per year, compared to 6.12 mL/min/1.73 m² per year in the placebo group, representing a 49.3% slower rate of decline .
• Kidney Failure Risk: The drug reduced the likelihood of progression to composite kidney failure events (including sustained 30% decline in kidney function, kidney function below 15, dialysis initiation, transplant, or death from kidney failure) by 43% .
• Protein in Urine: 40.7% of patients on Fabhalta achieved the target of sustained reduction of protein in urine below 1 gram per gram of creatinine, compared to 23.7% in the placebo group .

These improvements were consistent throughout the two-year follow-up period, suggesting that Fabhalta's benefits are sustained rather than temporary. The safety profile was also reassuring, with adverse event rates and treatment discontinuation rates similar between Fabhalta and placebo groups .

What Are the Most Common Side Effects?

The most frequently reported side effects with Fabhalta were mainly mild to moderate infections, such as COVID-19 and upper respiratory tract infections, along with headache, diarrhea, and elevated cholesterol levels. Importantly, these adverse event rates were comparable to placebo, meaning the drug did not introduce unexpected safety concerns beyond what patients might experience without treatment .

What's Next for Patients and the Healthcare System?

Fabhalta has already received accelerated approval from the U.S. Food and Drug Administration (FDA) and regulatory approval in China for reducing protein in urine in adults with IgAN. The two-year data have been submitted to the FDA for traditional approval, and the agency has granted the medication priority review status based on its novel mechanism of action and the strength of the clinical evidence .

"Persistent kidney inflammation is a hallmark of IgAN, and a key driver of disease progression, leading to ongoing kidney damage and loss of function over time. These results are important because they show that Fabhalta can reduce the risk of disease progression, help preserve kidney health, and address outcomes associated with long-term disease burden," said Vlado Perkovic, MD, Professor of Medicine and Provost at the University of New South Wales and Steering Committee Co-Chair of the APPLAUSE-IgAN study.

Vlado Perkovic, MD, Professor of Medicine and Provost, University of New South Wales

Beyond Fabhalta, the pharmaceutical company Novartis is advancing a multi-asset portfolio for IgAN that includes another medication called Vanrafia (atrasentan) and an investigational compound called zigakibart. This multi-pronged approach reflects the growing recognition that kidney disease requires targeted, mechanism-based treatments rather than one-size-fits-all approaches .

Why Does This Matter for the Broader Kidney Disease Community?

Chronic kidney disease (CKD) affects more than 35 million adults in the United States, yet approximately 90% of those affected do not know they have it. About 1 in 3 U.S. adults are at risk for kidney disease, with risk factors including diabetes, high blood pressure, heart disease, obesity, and family history. The burden of kidney disease is not equally distributed; Black or African American people are about four times as likely as White people to develop kidney failure, and Hispanic people experience kidney failure at approximately double the rate of White people .

The success of Fabhalta in slowing IgAN progression demonstrates that targeted therapies addressing the underlying causes of kidney disease can work. This breakthrough may inspire similar precision medicine approaches for other kidney conditions, potentially transforming the treatment landscape from one focused on managing end-stage disease to one that prevents or delays kidney failure altogether.

How to Discuss Fabhalta With Your Doctor

• Ask About Eligibility: If you have been diagnosed with IgA nephropathy and have persistent protein in your urine despite taking other medications, ask your nephrologist whether Fabhalta might be appropriate for you based on your specific kidney function and disease stage.
• Understand the Mechanism: Request an explanation of how Fabhalta works differently from your current treatment plan, and discuss whether adding or switching to this medication aligns with your long-term kidney health goals.
• Review Monitoring Requirements: Clarify what blood tests and follow-up appointments will be needed if you start Fabhalta, and discuss how your doctor will measure whether the medication is slowing your kidney disease progression.
• Discuss Side Effect Management: Talk with your doctor about the most common side effects, particularly infections, and develop a plan for managing them, especially if you have other health conditions or take immunosuppressive medications.

The APPLAUSE-IgAN study results represent a meaningful advance in kidney disease treatment, offering patients with IgAN a new option to slow disease progression and preserve kidney function. As more targeted therapies emerge, the field of nephrology is shifting toward precision medicine approaches that address the specific biological drivers of kidney disease rather than relying solely on general supportive care.