Novartis presented results from a pre-specified interim analysis of the Phase III APPLAUSE-IgAN study of Fabhalta (iptacopan), an investigational Factor B inhibitor of the alternative complement pathway, in patients with IgA nephropathy (IgAN)1. In the analysis, patients treated with Fabhalta achieved a 38.3% (p) Proteinuria reduction is an increasingly recognized surrogate marker correlating with progression to kidney failure and has been used as an endpoint in IgAN clinical trials to support accelerated approvals7. The study also showed that Fabhalta was well tolerated with a favorable safety profile consistent with previously reported data1,8. Results were presented during a late-breaking clinical trials session at the World Congress of Nephrology (WCN) in Buenos Aires, Argentina. This pre-specified interim analysis included 250 patients for the efficacy analysis and 443 for the safety analysis1.

The APPLAUSE-IgAN study continues in a double-blind fashion, and therefore only limited interim analysis results can be presented9,10. Submission for possible accelerated approval to the FDA was accepted and has received priority review. The primary endpoint evaluating Fabhalta's ability to slow IgAN progression by measuring the annualized total estimated glomerular filtration rate (eGFR) slope over 24 months is expected at study completion in 2025. Other data presented at WCN include IgAN and C3 glomerulopathy (C3G) real-world studies.

Novartis will be presenting further data from the renal portfolio at future medical meetings. APPLAUSE-IgAN (NCT04578834) is a Phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of twice-daily oral Fabhalta (200 mg) in 518 adult primary IgAN patients. The two primary endpoints of the study for the interim and final analysis, respectively, are proteinuria reduction at 9 months as measured by UPCR, and the annualized total eGFR slope over 24 months. At the time of final analysis, the following secondary endpoints will also be assessed: proportion of participants reaching UPCR <1 g/g without receiving corticosteroids/immunosuppressants or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating kidney replacement therapy (KRT), time from randomization to first occurrence of composite kidney failure endpoint event (reaching either sustained =30% decline in eGFR relative to baseline or sustained eGFR <15 mL/min/1.73 m2 or maintenance dialysis or receipt of kidney transplant or death from kidney failure), change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.  The main study population enrolled patients with an eGFR =30 mL/min/1.73 m2 and UPCR =1 g/g at baseline.

In addition, a smaller cohort of patients with severe renal impairment (eGFR 20?30 mL/min/1.73 m2 at baseline) was also enrolled to provide additional information but will not contribute to the main efficacy analyses. Discovered at Novartis, Fabhalta is currently in development for a range of rare diseases including IgAN, C3G, atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and lupus nephritis (LN). Fabhalta was approved by the FDA in December 2023 for the treatment of adults with the rare blood disorder paroxysmal nocturnal hemoglobinuria (PNH) and received a positive opinion from the CHMP of the EMA in March 2024.  IgAN is a heterogeneous, progressive, rare kidney disease2.

Each year, approximately 25 people per million worldwide are newly diagnosed with IgAN13. Up to 30% of people who have IgAN with persistent higher levels of proteinuria (=1 g/day) may progress to kidney failure within 10 years6. There is a need for effective, targeted therapies for IgAN that can help slow or prevent progression to kidney failure.