Results from the phase 3 APPLAUSE-IgAN trial, presented at the World Congress of Nephrology, demonstrated that patients with immunoglobulin A nephropathy (IgAN) who received iptacopan (Fabhalta; Novartis) achieved a significant reduction in proteinuria compared to those receiving placebo. Iptacopan is an oral Factor B inhibitor of the alternative complement pathway, a key part of the immune system involved in IgAN. The trial enrolled 518 patients with IgAN who were randomly assigned to receive either 200 mg of iptacopan twice daily or placebo with supportive care. The primary end points were proteinuria reduction at 9 months and annualized eGFR slope over 24 months. Interim analysis results, based on data from 250 patients, showed that iptacopan achieved a 38.3% proteinuria reduction (measured by urine protein creatinine ratio [UPCR]) at 9 months compared to placebo. The study also found that iptacopan was well-tolerated among patients, with a safety profile consistent with prior research.
IgAN is a heterogeneous and progressive kidney disease. Up to 30% of patients with IgAN have persistently higher levels of proteinuria (≥1 g/day), which may progress to kidney failure within 10 years. There is a need for effective targeted therapies that can slow or prevent the progression to kidney failure. Iptacopan, by specifically targeting the alternative complement pathway, offers a potential new treatment option for IgAN patients. The ongoing APPLAUSE-IgAN trial is expected to provide further insights into the long-term efficacy and safety of iptacopan in this population.
