Journal article
Iptacopan reduces proteinuria and stabilizes kidney function in C3 glomerulopathy
Kidney international reports, Vol.10(2), pp.432-446
02/2025
DOI: 10.1016/j.ekir.2024.10.023
PMCID: PMC11843281
PMID: 39990880
Abstract
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, selectively inhibiting the alternative complement pathway.
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.
At 12 months, patients in Cohort A had a significant reduction in 24-h urine protein–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/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 h 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/1.73 m2; p=0.7335; CI: -6.60, 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, 4.00;) at 9–12 months treatment with iptacopan.
These data provide a clinical rationale for further evaluation of long-term treatment of C3G with iptacopan.
Details
- Title: Subtitle
- Iptacopan reduces proteinuria and stabilizes kidney function in C3 glomerulopathy
- Creators
- Carla M. Nester - Stead Family Children’s Hospital – University of Iowa, Iowa City, IA, United StatesUte Eisenberger - University of Duisburg-EssenAlexandre Karras - Hôpital Européen Georges-PompidouMoglie le Quintrec - Centre Hospitalier Universitaire de MontpellierLiz Lightstone - Imperial College LondonManuel Praga - Universidad Complutense de MadridGiuseppe Remuzzi - Mario Negri Institute for Pharmacological ResearchMaria José Soler - Vall d'Hebron Hospital UniversitariJunhao Liu - Novartis Pharmaceuticals Corporation, East Hanover, NJ, United StatesMatthias Meier - Novartis (Netherlands)Ronda Tawfik - Novartis Pharmaceuticals Corporation, East Hanover, NJ, United StatesGuido Junge - Novartis Institutes for BioMedical ResearchAndrea Biondani - Novartis Institutes for BioMedical ResearchAngelo J. Trapani - NovartisNicholas JA Webb - Novartis (Netherlands)Edwin KS Wong - Newcastle University
- Resource Type
- Journal article
- Publication Details
- Kidney international reports, Vol.10(2), pp.432-446
- DOI
- 10.1016/j.ekir.2024.10.023
- PMID
- 39990880
- PMCID
- PMC11843281
- NLM abbreviation
- Kidney Int Rep
- ISSN
- 2468-0249
- eISSN
- 2468-0249
- Publisher
- Elsevier Inc
- Grant note
- Novartis Pharma AG
This study was funded by Novartis Pharma AG.
- Language
- English
- Electronic publication date
- 10/2024
- Date published
- 02/2025
- Academic Unit
- Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984742654602771
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