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Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy: 12-Month Results from the Phase 3 APPEAR-C3G Study: SA-OR66
Abstract   Peer reviewed

Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy: 12-Month Results from the Phase 3 APPEAR-C3G Study: SA-OR66

Carla M. Nester, Richard J. Smith, David Kavanagh, Marina Vivarelli, Giuseppe Remuzzi, Ming-Hui Zhao, Edwin Kwan Soon Wong, Yaqin Wang, Angelo J. Trapani, Induja Krishnan, …
Journal of the American Society of Nephrology, Vol.35(10S)
10/2024
DOI: 10.1681/ASN.2024f5gka890

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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, double-blind, 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. Conclusion: 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.

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