WCN25-2041 EFFICACY AND SAFETY OF IPTACOPAN IN PATIENTS WITH C3 GLOMERULOPATHY: 12-MONTH RESULTS FROM THE PHASE 3 APPEAR-C3G STUDY

Abstract

Background: The Phase 3 APPEAR-C3G study evaluated the efficacy, safety, and tolerability of iptacopan vs placebo in C3G patients (pts). Methods: APPEAR-C3G (NCT04817618) was a multicenter, randomized, doubleblind, placebo-controlled, pivotal Phase 3 study that included adult pts with biopsy confirmed C3G. The study comprised a 6 month (m) randomized double-blinded treatment with iptacopan 200mg bid. vs. placebo followed by 6m open-label iptacopan treatment, as previously described.1 Results: 74 pts were randomized 1:1 to either iptacopan (n=38) or placebo (n=36). Baseline pt demographics were generally balanced; the iptacopan arm exhibited a more severe disease phenotype. 43 (58.1%) pts in the iptacopan (n=22) and placebo (n=21) arms completed 12m treatment at data cut-off (when all pts completed 6m of treatment). The study met its primary endpoint, demonstrating a statistically significant reduction in 24h UPCR with iptacopan treatment at 6m (35.1%, 1-sided p=0.0014, 95% CI:13.8%, 51.1%) vs. placebo, sustained up to 12m (Figure). Iptacopan showed a sustained improvement in pts meeting the composite renal endpoint (≥50% reduction UPCR + ≤15% reduction in eGFR at 12m), 43.5% (iptacopan vs. placebo) and 25.0% (switched to iptacopan). Iptacopan led to improvements in the trajectory of eGFR compared to pts' historical eGFR decline. Iptacopan demonstrated a favorable safety profile with no new safety signals identified. Other 12m primary and key secondary endpoints will be presented. Conclusions: Iptacopan demonstrated a significant and clinically meaningful proteinuria reduction on top of supportive care at 6m in the APPEAR-C3G study; sustained up to 12m. Iptacopan was well tolerated with a favorable safety profile in C3G pts. Reference: 1. Bomback AS, et al. Kidney Int Rep. 2022;7:2150-9.