Fabhalta Secures Full FDA Approval to Slow Kidney Function Decline in IgA Nephropathy

Novartis has received traditional approval from the U.S. Food and Drug Administration for Fabhalta (iptacopan) to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk of disease progression. The decision converts the drug’s accelerated approval granted in August 2024, which was based on reducing proteinuria, into full approval supported by long-term clinical outcomes demonstrating preservation of kidney function.

Phase III APPLAUSE-IgAN Trial Confirmed Kidney Function Benefit

The approval is supported by results from the Phase III APPLAUSE-IgAN trial (NCT04578834), which showed that Fabhalta significantly slowed the decline in estimated glomerular filtration rate (eGFR), a key measure of kidney function, over two years of treatment.

Patients treated with Fabhalta experienced an annualized mean eGFR decline of −3.0 mL/min/1.73 m² per year, compared with −5.7 mL/min/1.73 m² per year in the placebo group, representing a 48% reduction in kidney function decline. The study also demonstrated clinically meaningful reductions in proteinuria as early as two weeks after treatment initiation, with benefits sustained throughout the study period.

The findings provide evidence that targeting complement activation can slow progression of IgAN beyond reducing urinary protein levels.

Targeting the Alternative Complement Pathway

Fabhalta is the first oral Factor B inhibitor approved for IgAN. The therapy selectively blocks the alternative complement pathway, a major contributor to glomerular inflammation and progressive kidney injury in the disease.

IgA nephropathy is a chronic autoimmune kidney disorder characterized by deposition of immunoglobulin A in the kidneys, triggering inflammation and progressive loss of kidney function. Approximately 25 people per million are newly diagnosed worldwide each year. Despite supportive care, up to half of patients with persistent proteinuria develop kidney failure within 10 to 20 years, often requiring dialysis or kidney transplantation.

By targeting a key driver of complement-mediated inflammation, Fabhalta offers a disease-modifying approach intended to preserve kidney function.

Safety Profile Remained Consistent

The Phase III study reported a safety profile consistent with previous clinical experience.

The most frequently reported adverse events included abdominal pain, dizziness, and nausea. Because complement inhibition increases susceptibility to serious infections caused by encapsulated bacteria, Fabhalta is available only through a Risk Evaluation and Mitigation Strategy (REMS) program. Patients must receive appropriate vaccinations before starting treatment.

Experts Highlight Importance of Preserving Kidney Function

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 slowing kidney function decline remains one of the most important treatment goals for patients with IgAN. She noted that the approval reinforces the clinical value of targeting complement activation as an underlying disease mechanism.

Bonnie Schneider, Director and Co-Founder of the IgA Nephropathy Foundation, said the approval offers renewed hope for patients and families living with a progressive disease that can ultimately lead to kidney failure.

Victor Bultó, President of Novartis US, stated that the approval further establishes Fabhalta’s role in preserving kidney function and reflects the company’s continued focus on developing therapies that address the underlying causes of kidney disease.

Expanding Novartis’ IgAN Portfolio

Fabhalta becomes a central component of Novartis’ growing immunoglobulin A nephropathy portfolio, which also includes Vanrafia (atrasentan) and the investigational therapy zigakibart. The company said expanding treatment options with different mechanisms of action may help clinicians better individualize therapy for patients with IgAN.

Novartis also stated that eligible U.S. patients will have access to support programs, with nearly all commercially insured patients expected to pay $10 or less per month for Fabhalta.

The traditional FDA approval marks an important milestone for Fabhalta by confirming that complement inhibition not only lowers proteinuria but also delivers sustained preservation of kidney function, addressing a critical long-term goal in the treatment of IgA nephropathy.

Reference

Novartis Fabhalta® (iptacopan) receives FDA traditional approval as first and only complement inhibitor to significantly slow kidney function decline in primary IgAN | Novartis