Interim results from the phase 3 APPLAUSE-IgAN study showed a statistically significant reduction in proteinuria among patients treated with iptacopan compared to placebo.
Norvartis Pharmaceuticals has announced positive topline results from the prespecified interim analysis of the phase 3 APPLAUSE-IgAN study evaluating the efficacy and safety of iptacopan in patients with primary immunoglobulin A nephropathy (IgAN).
Announced on October 2, 2023, Novartis intends to submit for possible accelerated approval with the US Food and Drug Administration (FDA) in 2024, with interim results showing iptacopan met the first primary endpoint of statistically significant proteinuria reduction versus placebo.1
“These positive data from the Phase III APPLAUSE study reinforce the potential of iptacopan to provide clinically meaningful benefit to patients with IgAN, a debilitating disease that affects mostly young adults,” said Shreeram Aradhye, MD, President, Development and Chief Medical Officer of Novartis.1 “We are excited about this milestone in the development of our factor B inhibitor of the alternative complement pathway and remain focused on further advancing our portfolio of renal programs through pivotal trials.”
An oral, proximal complement inhibitor, iptacopan binds factor B and inhibits the alternative complement pathway. It is currently in development for multiple complement-mediated diseases, including paroxysmal nocturnal hemoglobinuria, IgAN, C3 glomerulopathy, immune complex membranoproliferative glomerulonephritis, and atypical hemolytic uremic syndrome. APPLAUSE-IgAN is the third positive phase 3 trial for iptacopan. Of note, iptacopan is currently under regulatory review for paroxysmal nocturnal hemoglobinuria in the US.1
APPLAUSE-IgAN is a multicenter, randomized, double-blind, placebo-controlled study assessing proteinuria reduction and disease progression in patients with primary IgAN treated with twice-daily oral iptacopan 200mg compared to placebo. To be included in the study, participants were required to be ≥ 18 years of age with an estimated glomerular filtration rate (eGFR) level and biopsy-confirmed IgA nephropathy, have proteinuria due to primary diagnosis of IgA nephropathy as assessed at screening by UPCR ≥1 g/g, be vaccinated against Neisseria meningitidis and Streptococcus pneumoniae infection, and have been on a stable dose regimen of angiotensin converting enzyme inhibitors or angiotensin receptor blockers for approximately 90 days before first study drug administration.2
In total, 470 participants were enrolled in the study, including 430 biopsy-proven IgAN participants with eGFR ≥30 mL /min/1.73m2 in the main study population and 40 participants with eGFR 20 to <30 mL/min/1.73m2 forming a severe renal impairment population, randomized to treatment with iptacopan 200mg or placebo. The primary outcomes of interest are proteinuria reduction at 9 months as measured by urine protein to creatinine ratio (UPCR) and the annualized total eGFR slope over 24 months. Secondary endpoints include the proportion of participants reaching UPCR <1g/g, time from randomization to first occurrence of composite kidney failure endpoint event, and change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.1,2
According to the release, iptacopan demonstrated superiority versus placebo in proteinuria reduction and demonstrated a safety profile consistent with previously reported data. Topline results are expected in 2025 as the study continues to evaluate iptacopan’s ability to slow IgAN progression by measuring eGFR slope over 24 months.1