Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy
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 c...
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Elsevier
2025-02-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924019892 |
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| author | Carla M. Nester Ute Eisenberger Alexandre Karras Moglie le Quintrec Liz Lightstone Manuel Praga Giuseppe Remuzzi Maria José Soler Junhao Liu Matthias Meier Ronda Tawfik Guido Junge Andrea Biondani Angelo J. Trapani Nicholas J.A. Webb Edwin K.S. Wong |
| author_facet | Carla M. Nester Ute Eisenberger Alexandre Karras Moglie le Quintrec Liz Lightstone Manuel Praga Giuseppe Remuzzi Maria José Soler Junhao Liu Matthias Meier Ronda Tawfik Guido Junge Andrea Biondani Angelo J. Trapani Nicholas J.A. Webb Edwin K.S. Wong |
| author_sort | Carla M. Nester |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ac7cd479cb954f7a940e621c02a3d6cd |
| institution | Kabale University |
| issn | 2468-0249 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| spelling | doaj-art-ac7cd479cb954f7a940e621c02a3d6cd2025-08-20T03:47:09ZengElsevierKidney International Reports2468-02492025-02-0110243244610.1016/j.ekir.2024.10.023Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 GlomerulopathyCarla M. Nester0Ute Eisenberger1Alexandre Karras2Moglie le Quintrec3Liz Lightstone4Manuel Praga5Giuseppe Remuzzi6Maria José Soler7Junhao Liu8Matthias Meier9Ronda Tawfik10Guido Junge11Andrea Biondani12Angelo J. Trapani13Nicholas J.A. Webb14Edwin K.S. Wong15Stead Family Children’s Hospital-University of Iowa, Iowa City, Iowa, USA; Correspondence: Carla M. Nester, Stead Family Children’s Hospital-University of Iowa, 285 Newton Road, 5294 CBRB, Iowa City, Iowa 52242-1081, USA.Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyHôpital Européen Georges Pompidou, Paris, Île-de-France, FranceService de Néphrologie et Transplantation Rénale, Centre Hospitalier Universitaire de Montpellier, Montpellier, FranceDepartment of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, UK; Imperial College Renal and Transplant Centre, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UKDepartment of Medicine, Complutense University, Hospital Universitario 12 de Octubre, Madrid, SpainIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, ItalyNephrology Department, Hospital Universitari Vall d’Hebron, Barcelona, Catalunya, SpainNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USANovartis Pharma AG, Basel, Basel-Stadt, SwitzerlandNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USADepartment of Translational Medicine, Novartis Institutes for BioMedical Research, Basel, Basel-Stadt, SwitzerlandDepartment of Translational Medicine, Novartis Institutes for BioMedical Research, Basel, Basel-Stadt, SwitzerlandNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USANovartis Pharma AG, Basel, Basel-Stadt, SwitzerlandNewcastle University, Newcastle upon Tyne, UK; National Renal Complement Therapeutics Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UKIntroduction: 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.http://www.sciencedirect.com/science/article/pii/S2468024924019892C3 glomerulopathyC3Gcomplement pathwayiptacopankidneytransplantation |
| spellingShingle | Carla M. Nester Ute Eisenberger Alexandre Karras Moglie le Quintrec Liz Lightstone Manuel Praga Giuseppe Remuzzi Maria José Soler Junhao Liu Matthias Meier Ronda Tawfik Guido Junge Andrea Biondani Angelo J. Trapani Nicholas J.A. Webb Edwin K.S. Wong Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy Kidney International Reports C3 glomerulopathy C3G complement pathway iptacopan kidney transplantation |
| title | Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy |
| title_full | Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy |
| title_fullStr | Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy |
| title_full_unstemmed | Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy |
| title_short | Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy |
| title_sort | iptacopan reduces proteinuria and stabilizes kidney function in c3 glomerulopathy |
| topic | C3 glomerulopathy C3G complement pathway iptacopan kidney transplantation |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924019892 |
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