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

Introduction:

Complement 3 glomerulopathy (C3G), is an ultra-rare primary glomerulonephritis caused by the overactivation of the alternative complement pathway (AP). Iptacopan (LNP023) is an oral, proximal complement inhibitor that specifically targets factor B and inhibits the AP. Here we present the 12-month data from the pivotal APPEAR-C3G Phase 3 study, conducted to evaluate the efficacy, safety, and tolerability of iptacopan compared to placebo on top of supportive care in patients with native C3G

Methods:

APPEAR-C3G (NCT04817618) was a multicenter, randomized, double-blind, placebo-controlled, pivotal Phase 3 study that included adult patients with biopsy confirmed C3G. The study comprised 3 periods with a screening period (≤90 days), followed by randomized double-blinded treatment with iptacopan 200 mg b.i.d. vs. placebo (6 months) and open-label iptacopan treatment (6 months), as previously described[1].

Results:

74 patients 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%) patients in the iptacopan (n=22) and placebo (n=21) arms completed 12 months treatment at data cut-off (when all patients completed 6 months of treatment). The study met its primary endpoint, demonstrating a statistically significant reduction in 24h UPCR with iptacopan treatment at 6 months (35.1%, 1-sided p=0.0014, 95% CI:13.8%, 51.1%) vs. placebo, sustained up to 12 months (Figure). Iptacopan showed a sustained improvement in patients 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 patients historical eGFR decline. Iptacopan demonstrated a favorable safety profile with no new safety signals identified. Other 12-month primary and key secondary endpoints will be presented.  

Conclusions:

Iptacopan demonstrated a significant and clinically meaningful proteinuria reduction on top of supportive care at 6 months in the APPEAR-C3G study; sustained up to 12 months. Iptacopan was well tolerated with a favorable safety profile in C3G patients.

This abstract was also submitted for the ASN Congress in 2024.

Reference: 

1. Bomback AS, et al. Kidney Int Rep. 2022;7:2150–9

I have potential conflict of interest to disclose.
Clinical trial research support from Biocryst, Achillion, Novartis, Apellis, consulting fee from Silence Therapeutics; and participated on data safety monitoring board of Kira

I did not use generative AI and AI-assisted technologies in the writing process.