December 11, 2023
Iptacopan's Success in C3 Glomerulopathy Treatment Unveiled in Novartis Phase III Study
Novartis has revealed positive outcomes from the Phase III APPEAR-C3G study, showcasing the effectiveness of iptacopan in treating patients with C3 glomerulopathy (C3G). The study, which spanned six months, successfully met its primary endpoint, demonstrating iptacopan's superiority over a placebo in achieving clinically significant and statistically significant reduction in proteinuria (protein in urine) when added to background therapy. The safety profile of iptacopan remained consistent with previously reported data.
C3 glomerulopathy is an extremely rare kidney disease, primarily mediated by the complement system, with about 50% of patients progressing to kidney failure within a decade of diagnosis. Currently, there are no treatments targeting the root cause of C3G.
Iptacopan also demonstrated positive Phase III results in IgA nephropathy (IgAN) during the interim analysis, contributing to its ongoing late-stage development program across four investigational indications.
The Phase III APPEAR-C3G study will continue with a six-month open-label period, during which all patients, including those who initially received a placebo, will be administered iptacopan. Furthermore, enrollment is actively underway for a separate cohort involving adolescent patients with C3G.
The APPEAR-C3G study (NCT04817618) is a multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase III investigation evaluating the efficacy and safety of oral iptacopan (200 mg twice daily) in C3G patients. The study, designed for both adult and adolescent patients, involves a six-month double-blind phase, where patients are randomized to receive iptacopan or placebo alongside background therapy. This is followed by a six-month open-label phase, ensuring all patients receive iptacopan, regardless of their initial treatment allocation.
The primary endpoint for the initial six-month period was the reduction of proteinuria at six months, measured by urine protein to creatinine ratio (UPCR). The open-label period's primary endpoint is proteinuria reduction at 12 months for both treatment arms, with a comparison of proteinuria reduction between 6 and 12 months for the placebo arm. Secondary endpoints include changes in estimated glomerular filtration rate (eGFR), the proportion of participants meeting composite renal endpoint criteria, changes in glomerular inflammation, alterations in patient-reported fatigue, and safety and tolerability assessments.
C3 glomerulopathy (C3G) is an exceptionally rare kidney disease driven by complement-mediated processes, often initiating in children and young adults. Each year, roughly 1-2 individuals per million worldwide receive a new diagnosis of C3G, a specific type of membranoproliferative glomerulonephritis (MPGN).