Novartis reveals Phase III Fabhalta® data in C3G: 35.1% proteinuria reduction vs. placebo

Novartis has announced promising results from the Phase III APPEAR-C3G study on Fabhalta® (iptacopan), presented at the European Renal Association (ERA) Congress. The trial showed that patients with C3 glomerulopathy (C3G) who received Fabhalta in addition to supportive care experienced a significant 35.1% reduction in proteinuria over a 6-month period compared to placebo. Proteinuria reduction is an important marker as it correlates with slowing the progression to kidney failure.

Fabhalta, an oral inhibitor of Factor B in the alternative complement pathway, aims to address the underlying causes of C3G. This rare kidney disease, characterized by the overactivation of the alternative complement pathway, often leads to kidney failure within a decade for about half of the patients. Currently, no approved treatments exist for C3G, making these findings particularly hopeful.

Alongside the primary endpoint of proteinuria reduction, secondary endpoint data indicated a numerical improvement in the estimated glomerular filtration rate (eGFR), a key measure of kidney function. The safety profile of Fabhalta remained favorable, with no new safety signals reported. Regulatory submissions to the FDA and EMA for Fabhalta's use in adults with C3G are planned for the latter half of 2024.

Marianne Silkjær Nielsen, Founder of the Danish non-profit CompCure, emphasized the severe prognosis of C3G, highlighting the urgent need for treatments. She expressed optimism about the potential of new therapies to improve patient outcomes and mitigate the disease's impact.

Professor David Kavanagh from Newcastle University noted the significance of Fabhalta potentially being the first treatment to specifically target the alternative complement pathway in C3G. He underscored that current treatments do not address the disease's root causes and often bring considerable side effects. The encouraging results from the APPEAR-C3G study present a promising future for C3G treatment.

The APPEAR-C3G study consists of a 6-month double-blind period followed by a 6-month open-label period where all participants receive Fabhalta. Upcoming data from the open-label period will be presented at a future medical meeting.

At the ERA Congress, Novartis also unveiled data on other rare diseases, including investigational results for atrasentan in IgA nephropathy (IgAN) and long-term efficacy and safety data for Fabhalta in C3G.

David Soergel, Global Head of Cardiovascular, Renal, and Metabolism Development Unit at Novartis, reiterated the company's dedication to transforming treatment for patients with rare kidney diseases. The APPEAR-C3G results contribute to the growing evidence of Fabhalta's efficacy in providing meaningful clinical outcomes in various rare conditions.

The APPEAR-C3G trial is a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Fabhalta in C3G patients. The study is also enrolling adolescent patients in a separate cohort. The primary endpoint for the double-blind period was the 6-month reduction in proteinuria, while secondary endpoints included changes in eGFR, composite renal endpoint criteria, glomerular inflammation, patient-reported fatigue, and safety.

Fabhalta has been approved by the FDA and EMA for treating paroxysmal nocturnal hemoglobinuria (PNH), but its safety and efficacy in other conditions like IgAN, aHUS, and lupus nephritis are still under investigation.

C3G, a rare kidney disease often affecting children and young adults, involves overactivation of the immune system's alternative complement pathway. This leads to protein deposits in kidney glomeruli, causing inflammation, proteinuria, hematuria, and reduced kidney function. Around 50% of C3G patients advance to kidney failure within 10 years, necessitating dialysis or transplantation.

Novartis continues its commitment to nephrology, exploring innovative treatments aimed at preserving kidney function and improving the lives of those with rare kidney diseases.