Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis
Introduction: Complement 3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) have high risks for disease recurrence and allograft loss in transplant kidneys. Pegcetacoplan (targeted complement 3 [C3]/C3b inhibitor) may prevent excessive deposition of...
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Elsevier
2025-01-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924019612 |
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| author | Andrew S. Bomback Erica Daina Giuseppe Remuzzi John Kanellis David Kavanagh Matthew C. Pickering Gere Sunder-Plassmann Patrick D. Walker Zhongshen Wang Zurish Ahmad Fadi Fakhouri |
| author_facet | Andrew S. Bomback Erica Daina Giuseppe Remuzzi John Kanellis David Kavanagh Matthew C. Pickering Gere Sunder-Plassmann Patrick D. Walker Zhongshen Wang Zurish Ahmad Fadi Fakhouri |
| author_sort | Andrew S. Bomback |
| collection | DOAJ |
| description | Introduction: Complement 3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) have high risks for disease recurrence and allograft loss in transplant kidneys. Pegcetacoplan (targeted complement 3 [C3]/C3b inhibitor) may prevent excessive deposition of C3 and complement 5 [C5] breakdown products and associated renal damage. Methods: NOBLE (NCT04572854) is a prospective, phase 2, multicenter, open-label, randomized controlled trial evaluating the efficacy and safety of pegcetacoplan in posttransplant patients with recurrent C3G or IC-MPGN. The primary end point was reduction in C3c staining on renal biopsy at week 12 for patients who received either pegcetacoplan 1080 mg twice weekly by subcutaneous infusion plus standard-of-care (SOC) or SOC only. Results: Ten patients received pegcetacoplan and 3 received SOC only through week 12. At week 12, 5 of 10 pegcetacoplan-treated patients (50%) achieved ≥2 orders of magnitude (OOM) reduction in C3 staining (4 of these 5 had 0 staining and absent electron microscopy deposits) and 8 of 10 (80%) achieved ≥1 OOM reduction; 1 of 3 (33%) SOC-only patients showed staining reduction. Mean C3G histology activity score decreased by >54% in 8 of 10 pegcetacoplan-treated patients (80.0%). Pegcetacoplan-treated patients with baseline urine protein-to-creatinine ratio (uPCR) ≥1000 mg/g showed a median (interquartile range [IQR]) 54.4% (–56.33 to –53.95) reduction in proteinuria at week 12. In addition, pegcetacoplan-treated patients showed stable estimated glomerular filtration rate (eGFR), reduced plasma sC5b-9, and increased serum C3. Pegcetacoplan was well-tolerated and most adverse events were mild/moderate. No discontinuations, treatment withdrawals, or deaths were reported. Conclusion: NOBLE demonstrated efficacy, safety, and tolerability of pegcetacoplan for patients with posttransplant recurrent C3G and primary IC-MPGN. |
| format | Article |
| id | doaj-art-186922f4731f4d6e8da5b03be55d332c |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Kidney International Reports |
| spelling | doaj-art-186922f4731f4d6e8da5b03be55d332c2025-08-20T02:06:05ZengElsevierKidney International Reports2468-02492025-01-01101879810.1016/j.ekir.2024.09.030Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative GlomerulonephritisAndrew S. Bomback0Erica Daina1Giuseppe Remuzzi2John Kanellis3David Kavanagh4Matthew C. Pickering5Gere Sunder-Plassmann6Patrick D. Walker7Zhongshen Wang8Zurish Ahmad9Fadi Fakhouri10Division of Nephrology, Columbia University Irving Medical Center, New York, New York, USAIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, ItalyDepartment of Nephrology, Monash Health and Centre for Inflammatory Diseases, Clayton, Australia; Department of Medicine, Monash Medical Centre, Clayton, AustraliaNational Renal Complement Therapeutics Centre, Newcastle University, UKImperial College, London, UKDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, AustriaDepartment of Renal Pathology, Arkana Laboratories, Little Rock, Arkansas, USAApellis Pharmaceuticals, Inc., Waltham, Massachusetts, USAApellis Pharmaceuticals, Inc., Waltham, Massachusetts, USALausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Correspondence: Fadi Fakhouri, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon, 1005, Lausanne, Switzerland.Introduction: Complement 3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) have high risks for disease recurrence and allograft loss in transplant kidneys. Pegcetacoplan (targeted complement 3 [C3]/C3b inhibitor) may prevent excessive deposition of C3 and complement 5 [C5] breakdown products and associated renal damage. Methods: NOBLE (NCT04572854) is a prospective, phase 2, multicenter, open-label, randomized controlled trial evaluating the efficacy and safety of pegcetacoplan in posttransplant patients with recurrent C3G or IC-MPGN. The primary end point was reduction in C3c staining on renal biopsy at week 12 for patients who received either pegcetacoplan 1080 mg twice weekly by subcutaneous infusion plus standard-of-care (SOC) or SOC only. Results: Ten patients received pegcetacoplan and 3 received SOC only through week 12. At week 12, 5 of 10 pegcetacoplan-treated patients (50%) achieved ≥2 orders of magnitude (OOM) reduction in C3 staining (4 of these 5 had 0 staining and absent electron microscopy deposits) and 8 of 10 (80%) achieved ≥1 OOM reduction; 1 of 3 (33%) SOC-only patients showed staining reduction. Mean C3G histology activity score decreased by >54% in 8 of 10 pegcetacoplan-treated patients (80.0%). Pegcetacoplan-treated patients with baseline urine protein-to-creatinine ratio (uPCR) ≥1000 mg/g showed a median (interquartile range [IQR]) 54.4% (–56.33 to –53.95) reduction in proteinuria at week 12. In addition, pegcetacoplan-treated patients showed stable estimated glomerular filtration rate (eGFR), reduced plasma sC5b-9, and increased serum C3. Pegcetacoplan was well-tolerated and most adverse events were mild/moderate. No discontinuations, treatment withdrawals, or deaths were reported. Conclusion: NOBLE demonstrated efficacy, safety, and tolerability of pegcetacoplan for patients with posttransplant recurrent C3G and primary IC-MPGN.http://www.sciencedirect.com/science/article/pii/S2468024924019612C3 glomerulopathycomplementimmune complex membranoproliferative glomerulonephritispegcetacoplanproteinuria |
| spellingShingle | Andrew S. Bomback Erica Daina Giuseppe Remuzzi John Kanellis David Kavanagh Matthew C. Pickering Gere Sunder-Plassmann Patrick D. Walker Zhongshen Wang Zurish Ahmad Fadi Fakhouri Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis Kidney International Reports C3 glomerulopathy complement immune complex membranoproliferative glomerulonephritis pegcetacoplan proteinuria |
| title | Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis |
| title_full | Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis |
| title_fullStr | Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis |
| title_full_unstemmed | Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis |
| title_short | Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis |
| title_sort | efficacy and safety of pegcetacoplan in kidney transplant recipients with recurrent complement 3 glomerulopathy or primary immune complex membranoproliferative glomerulonephritis |
| topic | C3 glomerulopathy complement immune complex membranoproliferative glomerulonephritis pegcetacoplan proteinuria |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924019612 |
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