ID | 61532 |
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Author |
Hillmen, Peter
the Department of Haematology, St. James’s University Hospital
Szer, Jeff
the Department of Clinical Haematology, Peter MacCallum Cancer Center and Royal Melbourne Hospital
Weitz, Ilene
Jane Anne Nohl Division of Hematology, Keck School of Medicine of USC
Röth, Alexander
the Department of Hematology, West German Cancer Center University Hospital Essen, University of Duisburg-Essen
Höchsmann, Britta
the Institute of Transfusion Medicine, University of Ulm and Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service and University Hospital Ulm
Panse, Jens
the Department of Oncology, Hematology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen
Usuki, Kensuke
the Department of Hematology, NTT Medical Center Tokyo
Griffin, Morag
the Department of Haematology, St. James’s University Hospital
Kiladjian, Jean-Jacques
Centre d’Investigations Cliniques, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris, Université de Paris
de Castro, Carlos
the Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University
Nishimori, Hisakazu
the Department of Hematology and Oncology, Okayama University Hospital
Kaken ID
researchmap
Tan, Lisa
Lisa Tan Pharma Consulting
Hamdani, Mohamed
Apellis Pharmaceuticals
Deschatelets, Pascal
Apellis Pharmaceuticals
Francois, Cedric
Apellis Pharmaceuticals
Grossi, Federico
Apellis Pharmaceuticals
Ajayi, Temitayo
Apellis Pharmaceuticals
Risitano, Antonio
the Hematology and BMT Unit, AORN San Giuseppe Moscati
Peffault de la Tour, Régis
the French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris, Université de Paris
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Abstract | Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease characterized by chronic complement-mediated hemolysis. C5 inhibition controls intravascular hemolysis in untreated PNH but cannot address extravascular hemolysis. Pegcetacoplan, a pegylated peptide targeting proximal complement protein C3, potentially inhibits both intravascular and extravascular hemolysis.
Methods
We conducted a phase 3 open-label, controlled trial to assess the efficacy and safety of pegcetacoplan as compared with eculizumab in adults with PNH and hemoglobin levels lower than 10.5 g per deciliter despite eculizumab therapy. After a 4-week run-in phase in which all patients received pegcetacoplan plus eculizumab, we randomly assigned patients to subcutaneous pegcetacoplan monotherapy (41 patients) or intravenous eculizumab (39 patients). The primary end point was the mean change in hemoglobin level from baseline to week 16. Additional clinical and hematologic markers of hemolysis and safety were assessed.
Results
Pegcetacoplan was superior to eculizumab with respect to the change in hemoglobin level from baseline to week 16, with an adjusted (least squares) mean difference of 3.84 g per deciliter (P<0.001). A total of 35 patients (85%) receiving pegcetacoplan as compared with 6 patients (15%) receiving eculizumab no longer required transfusions. Noninferiority of pegcetacoplan to eculizumab was shown for the change in absolute reticulocyte count but not for the change in lactate dehydrogenase level. Functional Assessment of Chronic Illness Therapy–Fatigue scores improved from baseline in the pegcetacoplan group. The most common adverse events that occurred during treatment in the pegcetacoplan and eculizumab groups were injection site reactions (37% vs. 3%), diarrhea (22% vs. 3%), breakthrough hemolysis (10% vs. 23%), headache (7% vs. 23%), and fatigue (5% vs. 15%). There were no cases of meningitis in either group.
Conclusions
Pegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients with PNH by providing broad hemolysis control, including control of intravascular and extravascular hemolysis. (Funded by Apellis Pharmaceuticals; PEGASUS ClinicalTrials.gov, NCT03500549. opens in new tab.)
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Note | From New England Journal of Medicine, Peter Hillmen et. al., Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria, 384, 1028-1037 Copyright © 2021 Massachusetts Medical Society. Reprinted with permission.
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Published Date | 2021-03-18
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Publication Title |
New England Journal of Medicine
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Volume | volume384
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Publisher | Massachusetts Medical Society
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Start Page | 1028
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End Page | 1037
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ISSN | 0028-4793
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NCID | AA00755156
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2021 Massachusetts Medical Society
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File Version | publisher
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PubMed ID | |
DOI | |
Related Url | isVersionOf https://doi.org/10.1056/NEJMoa2029073
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