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Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy: C3G Extension Trial Interim Results from the Phase 3 APPEAR-C3G Patients: FR-PO0838
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Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy: C3G Extension Trial Interim Results from the Phase 3 APPEAR-C3G Patients: FR-PO0838

Carla M. Nester, Richard J. Smith, David Kavanagh, Marina Vivarelli, Giuseppe Remuzzi, Ming-Hui Zhao, Edwin Kwan Soon Wong, Yaqin Wang, Rubeen K. Israni, Hari Varun Kalluri, …
Journal of the American Society of Nephrology, Vol.36(10S)
10/2025
DOI: 10.1681/ASN.202599z9n79j

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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. Upon completion of study treatment at 12m in APPEAR-C3G, participants had the option to continue open-label iptacopan treatment in the C3G extension study (NCT03955445). Here we present the results from the extension study with iptacopan treatment up to 24m. Results: Of 73 pts completing the 12m treatment, 66 pts entered the extension study. In the iptacopan arm, the geometric mean reduction in first morning void (FMV) UPCR at Month 12 (35.9%), was sustained up to Month 24 (34.2%) compared to baseline (Figure). In the placebo-iptacopan switch arm, the reduction at Month 12 (34.0%) was also sustained up to Month 24 (29.7%). The mean pre-treatment annualized eGFR slope (95%CI) in all pts (n=74) showed rapid decline with −7.22 mL/min/1.73m2/year (−10.10, −4.35). After initiation of iptacopan treatment, there was stabilization of annualized eGFR slope (95%CI) at −0.29 mL/min/1.73m2/year (−3.88, 3.31) assessed over 24 months. Iptacopan demonstrated a favorable safety profile with no new safety signals identified. Conclusion: Iptacopan demonstrated sustained reduction in proteinuria and stabilization of eGFR slope with treatment up to 24 months among APPEAR-C3G pts who rolled over to the long-term extension study. Iptacopan was well tolerated with a favorable safety profile in C3G pts.

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