FDA grants accelerated approval to Novartis' Fabhalta® (iptacopan) for reducing proteinuria in IgA nephropathy

Novartis has announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Fabhalta® (iptacopan), marking a significant milestone in the treatment of primary immunoglobulin A nephropathy (IgAN). Fabhalta, an innovative complement inhibitor, aims to reduce proteinuria in adults with IgAN who are at risk of rapid disease progression. This condition is generally identified by a urine protein-to-creatinine ratio (UPCR) of ≥1.5 g/g.

The approval was based on the interim analysis of the Phase III APPLAUSE-IgAN study, which evaluated the reduction in proteinuria over nine months compared to a placebo. Fabhalta specifically targets the alternative complement pathway of the immune system, which, when overly activated in the kidneys, contributes to the pathogenesis of IgAN. The study revealed that Fabhalta achieved a 44% reduction in proteinuria from baseline, compared to just a 9% reduction in the placebo group, demonstrating a statistically significant 38% reduction versus placebo.

The continued approval of Fabhalta is contingent upon the verification and description of clinical benefits from the ongoing Phase III APPLAUSE-IgAN study. This study is also evaluating whether Fabhalta slows disease progression as measured by the estimated glomerular filtration rate (eGFR) decline over 24 months, with the eGFR data expected at study completion in 2025.

IgAN is a rare and progressive disease where the immune system attacks the kidneys, leading to glomerular inflammation and proteinuria. It affects approximately 25 people per million worldwide each year. Despite current standard treatments, 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.

The primary endpoint of the APPLAUSE-IgAN study was the percentage reduction of proteinuria, measured by comparing UPCR at nine months to the baseline. Fabhalta demonstrated consistent treatment effects across all subgroups, including age, sex, race, and baseline disease characteristics. Additionally, Fabhalta showed a favorable safety profile, with the most common adverse reactions including upper respiratory tract infection, lipid disorders, and abdominal pain. However, Fabhalta may cause serious infections from encapsulated bacteria and is only available through a Risk Evaluation and Mitigation Strategy (REMS) requiring specific vaccinations.

"Today’s approval of Fabhalta as a first-in-class medicine for IgA nephropathy marks an important milestone in our journey to advance care for rare renal diseases," said Victor Bultó, President US, Novartis. "We are deeply committed to those living with such conditions and look forward to continued partnership with this community."

In addition to Fabhalta, Novartis is advancing two other therapies for IgAN: atrasentan, an oral endothelin A receptor antagonist, and zigakibart, an anti-APRIL monoclonal antibody. Both are in late-stage development, with atrasentan having received FDA filing acceptance earlier in 2024, and zigakibart currently in Phase III development.

Bonnie Schneider, Director and Co-Founder of the IgAN Foundation, expressed optimism about the approval of Fabhalta, highlighting its potential to provide new hope for people living with IgAN.

Novartis is also developing additional resources to help patients access their treatment through the comprehensive Novartis Patient Support program, which offers personalized assistance for navigating insurance coverage and identifying financial assistance options. This underscores Novartis's commitment to evolving the treatment landscape for rare renal diseases and improving patient outcomes.