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WCN26-5461 ORAL IPTACOPAN THERAPY IN C3 GLOMERULOPATHY SHOWS CONSISTENT STABILIZATION OF eGFR SLOPE ACROSS PATIENT SUBGROUPS
Abstract   Open access   Peer reviewed

WCN26-5461 ORAL IPTACOPAN THERAPY IN C3 GLOMERULOPATHY SHOWS CONSISTENT STABILIZATION OF eGFR SLOPE ACROSS PATIENT SUBGROUPS

David Kavanagh, Andrew S. Bomback, Carla M. Nester, Richard J.H. Smith, Liz Lightstone, Marina Vivarelli, Sophie Chauvet, Ming-Hui Zhao, Aiko PJ de Vries, Jean Grisouard, …
Kidney international reports, Vol.11(4 Supplement), 105746
04/2026
DOI: 10.1016/j.ekir.2026.105746
url
https://doi.org/10.1016/j.ekir.2026.105746View
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Abstract

Introduction C3 glomerulopathy (C3G) is an ultra-rare and severe form of primary chronic glomerulonephritis caused by overactivation of the alternative complement pathway (AP). Iptacopan is a proximal complement inhibitor that targets factor B to specifically inhibit the AP and was recently approved for the treatment of adult patients with C3G, representing the first oral targeted treatment approved for C3G. The APPEAR-C3G Phase 3 trial (NCT04817618) met its primary endpoint, demonstrating a statistically significant (p=0.0014) relative reduction in 24-hour urine protein–creatinine ratio (UPCR) of 35.1% (95% CI: 13.8% to 51.1%) with iptacopan treatment at 6 months vs placebo. The iptacopan arm had a baseline to 12 month sustained reduction of 40% in 24-hour UPCR, showing durability of the treatment effect. Iptacopan treatment in the APPEAR-C3G trial stabilized patients estimated glomerular filtration rate (eGFR) slope trajectory compared to pre-treatment decline. This analysis compares eGFR slope changes after iptacopan initiation to pre-treatment slopes across multiple C3G participant subgroups in the APPEAR-C3G study. Methods The APPEAR-C3G trial was a Phase 3, randomized, double-blind, placebo-controlled, multicenter study. It assessed the efficacy and safety of iptacopan, alongside supportive care, in adult participants with C3G . The study comprised a 6-month randomized double-blind treatment with iptacopan 200 mg twice daily vs. placebo, followed by 6 months of open-label iptacopan treatment . Pre-enrolment eGFR measurements (up to 2.5 years pre-randomization in the placebo arm, up to 2 years in the iptacopan arm) and post-iptacopan treatment values (6 months in the placebo arm, 12 months in the iptacopan arm) were assessed for changes in eGFR slope. Pre-enrolment eGFR values were based on historical source data verified serum creatinine collected prior to the study. The patient subgroups analyzed were i) baseline UPCR ≥3 g/g vs. <3 g/g, ii) baseline eGFR <90 vs. ≥90 mL/min/1.73 m2, and iii) with or without corticosteroid and/or mycophenolic acid treatment at randomization. Results 74 adult participants were randomized 1:1 to receive either iptacopan (n=38) or placebo (n=36), with 73 participants completing the 12-month study. Iptacopan reduced the rate of kidney function decline and stabilized eGFR slopes in all subgroups during the study treatment. In all subgroups evaluated, except those with eGFR ≥ 90ml/min/1.73m2, pre-treatment slopes were steeply negative, indicating a rapid loss of kidney function prior to iptacopan treatment. Iptacopan initiation resulted in an annualized eGFR slope between −1.75 and + 3.99 mL/min/1.73 m2/year (Table 1). These improvements in eGFR slope reflect consistent eGFR stabilization and suggest preservation of kidney function in participants with C3G following iptacopan treatment.

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