Novartis’ Fabhalta® (Iptacopan) Achieves Positive Phase III Results, Marking Major Progress in Slowing Kidney Function Decline in Patients With IgA Nephropathy
Novartis announced encouraging final results from its pivotal Phase III APPLAUSE-IgAN clinical trial, evaluating the investigational oral therapy Fabhalta® (iptacopan) in adults living with IgA nephropathy (IgAN). The results demonstrated that Fabhalta achieved statistically significant and clinically meaningful superiority compared to placebo in slowing disease progression, as measured by the annualized total slope of estimated glomerular filtration rate (eGFR) decline over two years. These findings underscore Fabhalta’s potential as a first-in-class, oral alternative complement pathway inhibitor designed to protect long-term kidney function in patients with this chronic autoimmune condition.
A Milestone in IgA Nephropathy Management
IgA nephropathy—also known as Berger’s disease—is a progressive autoimmune kidney disorder characterized by the deposition of immunoglobulin A (IgA) in the glomeruli, leading to inflammation and kidney damage. The disease typically manifests as hematuria (blood in urine), proteinuria (protein leakage), and a gradual decline in eGFR, a critical indicator of kidney function. Over time, this deterioration can lead to chronic kidney disease (CKD) and, in many cases, end-stage kidney failure, requiring dialysis or kidney transplantation.
Globally, Novartis approximately 25 per million people are newly diagnosed with IgAN each year. Despite advances in supportive care, which includes blood pressure control, dietary changes, and renin-angiotensin system (RAS) inhibition, no existing therapy fully addresses the underlying immune-driven inflammation that causes disease progression. Up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis.
This unmet need highlights the importance of new therapeutic approaches like Fabhalta that directly target the alternative complement pathway, a key driver of kidney inflammation and damage in IgAN.
Strong Phase III Data Demonstrate Significant Kidney Protection
The APPLAUSE-IgAN study was designed to evaluate the efficacy and safety of Fabhalta in reducing the rate of kidney function decline among adult patients with IgAN. Over a two-year treatment period, Fabhalta significantly slowed the annualized eGFR decline compared to placebo, meeting the study’s primary endpoint.
Novartis reported that Fabhalta demonstrated both statistical significance and clinical relevance in preserving kidney function—an outcome that could represent a paradigm shift in the treatment of IgAN, a condition historically associated with poor long-term outcomes.
“These Novartis results mark an exciting advancement in the field of nephrology,” said Ruchira Glaser, Development Unit Head, Cardiovascular, Renal & Metabolic, Novartis. “Progressive diseases such as IgAN present an urgent need for interventions that can ultimately improve kidney health. Many people with IgAN commonly experience fear and anxiety about disease progression. The positive results from the APPLAUSE-IgAN trial, showing slowed eGFR decline, add to the growing body of evidence supporting Fabhalta as a targeted therapy to preserve long-term kidney function, giving hope to people living with this condition.”
Fabhalta: A Targeted Oral Therapy Designed to Interrupt Disease Progression
Fabhalta (iptacopan) is an oral, first-in-class inhibitor of complement factor B, a key component of the alternative complement pathway (AP). This pathway is part of the body’s immune defense system, but when dysregulated—as in IgAN—it contributes to ongoing kidney inflammation and tissue damage.
By selectively blocking factor B, Fabhalta inhibits the activation of this destructive immune cascade, helping to reduce proteinuria and inflammation while preserving kidney function. Unlike some current therapies that address symptoms indirectly, Fabhalta acts upstream at the level of disease pathophysiology, potentially slowing or even halting disease progression.
The convenience of an oral formulation may also make Fabhalta a preferred option for long-term management compared to existing or investigational therapies requiring infusion or injection, improving patient adherence and quality of life.
Safety Profile and Tolerability
In the APPLAUSE-IgAN study, Fabhalta was well tolerated with a favorable safety profile, consistent with previously reported clinical data. No new or unexpected safety concerns emerged. This reassuring safety profile strengthens Fabhalta’s case as a viable treatment option for patients with chronic kidney disease driven by immune dysregulation.
Novartis confirmed that full data from the final analysis of APPLAUSE-IgAN will be presented at upcoming medical meetings, where detailed efficacy and safety results will provide further insights into Fabhalta’s potential clinical impact.
Regulatory Path and Expanding Kidney Portfolio
Building on the positive Phase III findings, Novartis plans to submit regulatory filings for Fabhalta in 2026. If approved, Fabhalta could become one of the first oral therapies to address the root cause of IgA nephropathy by modulating complement activation rather than simply managing its downstream effects.
Fabhalta is part of Novartis’ broader nephrology and renal innovation portfolio, which includes multiple complementary assets targeting various aspects of kidney disease biology. Among them are Vanrafia® (atrasentan), an endothelin A receptor antagonist approved for certain kidney conditions, and zigakibart, an investigational monoclonal antibody currently in development for IgAN and other renal disorders.
This multi-asset approach reflects Novartis’ long-term vision of transforming kidney disease management through precision medicine, early intervention, and improved patient outcomes.
The Human and Clinical Impact of IgA Nephropathy
Beyond its physical burden, IgAN imposes profound psychological, social, and economic challenges on patients and their families. Living with a chronic and unpredictable disease often causes anxiety, depression, and lifestyle disruptions, as patients manage the uncertainties of disease progression and the potential need for dialysis or transplantation.
Despite supportive care, many patients continue to experience worsening kidney function, and current therapies do not adequately address the underlying immune processes that drive the disease. The development of novel treatments like Fabhalta represents a long-awaited step toward disease modification, offering hope for more durable kidney preservation and improved quality of life.
A New Chapter for Kidney Care
The success of the APPLAUSE-IgAN trial positions Fabhalta as a potential game-changer in the treatment of IgA nephropathy. As the first oral therapy to demonstrate significant kidney protection through targeted complement inhibition, Fabhalta may soon redefine therapeutic standards for patients facing this progressive and life-altering disease.
With continued progress in its nephrology portfolio and a commitment to innovation in kidney health, Novartis is charting a new course for patients living with chronic kidney disease—turning scientific discovery into tangible hope for the millions affected by conditions like IgAN.
