Novartis is pleased to announce that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Fabhalta® (iptacopan), a groundbreaking first-in-class complement inhibitor. This approval is for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk of rapid disease progression, typically defined as a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g. Fabhalta targets the alternative complement pathway, whose overactivation in the kidneys is believed to play a role in the pathogenesis of IgAN.

Significant Interim Analysis Results

The accelerated approval is based on a pre-specified interim analysis of the Phase III APPLAUSE-IgAN study, which focused on proteinuria reduction over 9 months compared to placebo. The study results indicated a remarkable 44% reduction in proteinuria at 9 months from baseline with Fabhalta, compared to a 9% reduction in the placebo arm. This equates to a clinically significant and statistically robust 38% reduction vs. placebo (p<0.0001).

“The heterogeneous and progressive nature of IgA nephropathy has made it challenging to effectively treat this disease. Thankfully, the treatment landscape is rapidly evolving,” said Professor Dana Rizk, Investigator and APPLAUSE-IgAN Steering Committee Member and professor in the University of Alabama at Birmingham Division of Nephrology. “Mounting clinical evidence underscores the pivotal role of complement activation in IgA nephropathy. I am thrilled that this advancement is now available to help enable a targeted treatment approach for IgAN patients.”

 IgA Nephropathy

IgAN is a progressive, rare disease where the immune system attacks the kidneys, leading to glomerular inflammation and proteinuria. Each year, approximately 25 people per million worldwide are newly diagnosed with IgAN. Despite current standard care, up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years, necessitating maintenance dialysis or kidney transplantation.

Continued Approval Contingent on Further Study

The ongoing Phase III APPLAUSE-IgAN study continues to evaluate Fabhalta’s efficacy and safety. The study's primary endpoint is the percent reduction of proteinuria at 9 months compared to baseline, with further data expected on whether Fabhalta slows disease progression as measured by estimated glomerular filtration rate (eGFR) decline over 24 months. The eGFR data are anticipated to be available in 2025 to support traditional FDA approval.

Positive Safety Profile

Fabhalta has shown a favorable safety profile consistent with previously reported data. The most common adverse reactions (≥5%) were upper respiratory tract infection, lipid disorder, and abdominal pain. Fabhalta may cause serious infections by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires specific vaccinations.

Expanding Commitment in IgAN

“Today’s approval of Fabhalta as a first-in-class medicine for IgA nephropathy is an important milestone in our journey to evolve rare renal disease care by bringing new treatments to people in urgent need of options,” said Victor Bultó, President US, Novartis. “We are deeply committed to those living with rare renal diseases and look forward to continued partnership with this community as we further advance our broad portfolio.”

Novartis is also advancing the late-stage development of two additional IgAN therapies: atrasentan, an investigational oral endothelin A receptor antagonist, and zigakibart, an investigational subcutaneously administered anti-APRIL monoclonal antibody, both with highly differentiated mechanisms of action.

Patient Community Impact

“As a parent of a son living with the disease for 20 years, I understand firsthand the fear and uncertainty that come with an IgAN diagnosis, and the devastating impact it can have on patients and their families,” said Bonnie Schneider, Director and Co-Founder, IgAN Foundation. “Today’s approval offers new hope for people living with IgA nephropathy as it represents a treatment innovation that provides us with a new way to fight this multifaceted disease.”