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Lookup NU author(s): Dr Edwin Wong
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 International Society of Nephrology. Introduction: C3 glomerulopathy (C3G) is a complex, chronic, ultra rare, progressive primary glomerulonephritis, resulting from alternative complement pathway overactivation, leading to kidney failure in most patients, and frequent recurrence in transplants. Iptacopan (LNP023) is an oral, proximal complement inhibitor specifically targeting factor B, that selectively inhibits the alternative complement pathway. Methods: This was a phase 2 extension study of 26 adult patients with native kidney (cohort A), or recurrent C3G (post kidney transplantation; cohort B) receiving open label iptacopan. Results: At 12 months, patients in cohort A had a significant reduction in 24-hour urine protein-to-creatinine ratio (UPCR; 57%; P < 0.0001; confidence interval [CI]: 0.31–0.59), an improvement in estimated glomerular filtration rate (eGFR; 6.83 ml/min per 1.73 m2; P = 0.0174; CI: 1.25–12.40), and an increase in serum C3 levels (geometric mean ratio to baseline: 3.53; P < 0.0001; CI: 3.01–4.15). In cohort B, most patients had normal urinary protein excretion at baseline (mean [range] 24-hour UPCR: 121 [9–445]), which was slightly lower by 12 months (21% reduction; CI: 0.48–1.31; P = 0.3151). In cohort B at 12 months, mean eGFR was at baseline values (mean change from baseline: −0.96 ml/min per 1.73 m2; P = 0.7335; CI: −6.60 to 4.69). Cohort B patients had significantly higher serum C3 values at 12 months compared with baseline (ratio:1.96; CI: 1.70–2.27; P < 0.0001). In cohorts A + B combined, the median difference in C3 deposit score on renal biopsy from baseline was −7.00 (CI: −12.00 to 4.00;) at 9 to 12 months treatment with iptacopan. Conclusion: These data provide a clinical rationale for further evaluation of long-term treatment of C3G with iptacopan.
Author(s): Nester CM, Eisenberger U, Karras A, le Quintrec M, Lightstone L, Praga M, Remuzzi G, Soler MJ, Liu J, Meier M, Tawfik R, Junge G, Biondani A, Trapani AJ, Webb NJA, Wong EKS
Publication type: Article
Publication status: Published
Journal: Kidney International Reports
Year: 2024
Pages: Epub ahead of print
Online publication date: 28/10/2024
Acceptance date: 21/10/2024
Date deposited: 07/01/2025
ISSN (electronic): 2468-0249
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.ekir.2024.10.023
DOI: 10.1016/j.ekir.2024.10.023
Data Access Statement: Anonymized patient-level data from clinical trials may be shared by Novartis in a consortium called ClinicalStudyDataRequest.com (CSDR) in accordance with Novartis’ policy for sharing clinical trial data (https://www.clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Novartis.aspx).
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