Novartis AG presented results from the 6-month, double-blind period of the Phase III APPEAR-C3G study of Fabhalta (iptacopan) at the late-breaking clinical trials session of the European Renal Association (ERA) Congress. Patients treated with Fabhalta in addition to supportive care achieved a 35.1% (p=0.0014) reduction in proteinuria (as measured by 24-hour urine protein to creatinine ratio [UPCR') at 6 months when compared to placebo on top of supportive care1. Fabhalta is an oral Factor B inhibitor of the alternative complement pathway being investigated in adult patients with C3 glomerulopathy (C3G)1-3. Regulatory submissions, including to the FDA and EMA, for the adult C3G indication are planned for the second half of 2024.

The APPEAR-C3 G study continues with an additional 6-month, open-label period following the 6-month double-blind period, in which all patients receive Fabhalta, including those previously receiving placebo. These data will be presented at an upcoming medical meeting when available. At ERA, Novartis is also presenting new data across its rare disease portfolio, including results for investigational atrasentan in IgA nephropathy (IgAN) from the 36-week interim analysis of the Phase III ALIGN study, additional data for Fabhalta in IgAN from the 9-month interim analysis of the Phase III APPLAUSE-IgAN study, long-term 33-month efficacy and safety data for Fabhalta In C3G from the Phase II extension study, 1-year Phase I/II data for investigational zigakibart in IgAN, and data from real-world studies in C3G and atypical hemolytic uremic syndrome (aHUS)16-19.

Fabhalta was approved by the FDA in December 2023 and the EMA in May 2024 for the treatment of adults with the rare blood disorder paroxysmal nocturnal hemoglobinuria (PNH)21,22. C3G is an ultra-rare, progressive kidney disease that initially presents in mostly children and young adults4-6,23. Each year, approximately 1-2 people per million worldwide are newly diagnosed with C3G, a form of membranoproliferative glomerulonephritis (MPGN).

In C3G, overactivation of the alternative complement pathway ? part of the immune system ? causes deposits of C3 protein to build up in kidney glomeruli (a network of blood vessels that filter waste and remove extra fluids from the blood)4,7,23-25.

This triggers inflammation and glomerular damage that results in proteinuria (protein in urine), hematuria (blood in urine) and reduced kidney function4,7,23-25. Approximately 50% of C3G patients progress to kidney failure within 10 years of diagnosis, at which point they will require dialysis and/or kidney transplantation6,7, with over 55% of?patients?with C3G?experiencing disease recurrence post-transplant26-29.