3113 – FORTY-EIGHT WEEK EFFICACY AND SAFETY OF PEGCETACOPLAN IN ADULT PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA AND SUBOPTIMAL RESPONSE TO PRIOR ECULIZUMAB TREATMENT
Pegcetacoplan (PEG) is a C3 complement inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). PEG was superior to eculizumab (ECU; C5-inhibitor) in improving hemoglobin (Hb) levels and clinical outcomes at Week 16 (phase 3 PEGASUS trial NCT03500549). Here, we report efficacy and s...
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| Vydané v: | Experimental hematology Ročník 100; s. S97 |
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| Hlavní autori: | , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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Elsevier Inc
01.08.2021
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| ISSN: | 0301-472X, 1873-2399 |
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| Abstract | Pegcetacoplan (PEG) is a C3 complement inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). PEG was superior to eculizumab (ECU; C5-inhibitor) in improving hemoglobin (Hb) levels and clinical outcomes at Week 16 (phase 3 PEGASUS trial NCT03500549). Here, we report efficacy and safety of PEG through Week 48. Eighty PNH patients ≥18 years with Hb levels <10.5 g/dL despite stable ECU treatment (≥3 months) were enrolled. Patients completed a 4-week run-in with both ECU and PEG before 1:1 randomization to PEG (n=41) or ECU monotherapy (n=39). The primary endpoint was the change from baseline (CFB) in Hb to Week 16. Key secondary endpoints included adverse events (AEs). After the randomized control period (RCP), patients could continue to an open-label period (OLP), with a 4-week run-in for ECU patients (ECU-to-PEG), followed by PEG monotherapy for all patients through Week 48. Improved Hb levels observed at Week 16 were sustained during the OLP in PEG monotherapy patients. ECU-to-PEG patients experienced Hb improvement with mean Hb levels of 11.6 g/dL at Week 48 (CFB: 2.9 g/dL), while PEG-to-PEG patients maintained high Hb levels through the OLP with a mean Hb level of 11.3 g/dL at Week 48 (CFB: 2.6 g/dL). Serious AEs were reported by 30% of patients with 6% possibly related to PEG. Common AEs for PEG patients were injection site reactions (36%), hemolysis (24%), and diarrhea (21%). Overall, 12 patients (15%) discontinued PEG: 3 in RCP, 8 in OLP due to treatment-emergent AEs (6 in ECU-to-PEG, 2 in PEG-to-PEG), and one during follow-up; one patient withdrew due to physician decision. PEG-treated PNH patients experienced durable treatment effects in all efficacy parameters at Week 48 and the safety profile of PEG was consistent with previously reported data. The results suggest that PEG represents a new effective therapeutic option for PNH patients. |
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| AbstractList | Pegcetacoplan (PEG) is a C3 complement inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). PEG was superior to eculizumab (ECU; C5-inhibitor) in improving hemoglobin (Hb) levels and clinical outcomes at Week 16 (phase 3 PEGASUS trial NCT03500549). Here, we report efficacy and safety of PEG through Week 48. Eighty PNH patients ≥18 years with Hb levels <10.5 g/dL despite stable ECU treatment (≥3 months) were enrolled. Patients completed a 4-week run-in with both ECU and PEG before 1:1 randomization to PEG (n=41) or ECU monotherapy (n=39). The primary endpoint was the change from baseline (CFB) in Hb to Week 16. Key secondary endpoints included adverse events (AEs). After the randomized control period (RCP), patients could continue to an open-label period (OLP), with a 4-week run-in for ECU patients (ECU-to-PEG), followed by PEG monotherapy for all patients through Week 48. Improved Hb levels observed at Week 16 were sustained during the OLP in PEG monotherapy patients. ECU-to-PEG patients experienced Hb improvement with mean Hb levels of 11.6 g/dL at Week 48 (CFB: 2.9 g/dL), while PEG-to-PEG patients maintained high Hb levels through the OLP with a mean Hb level of 11.3 g/dL at Week 48 (CFB: 2.6 g/dL). Serious AEs were reported by 30% of patients with 6% possibly related to PEG. Common AEs for PEG patients were injection site reactions (36%), hemolysis (24%), and diarrhea (21%). Overall, 12 patients (15%) discontinued PEG: 3 in RCP, 8 in OLP due to treatment-emergent AEs (6 in ECU-to-PEG, 2 in PEG-to-PEG), and one during follow-up; one patient withdrew due to physician decision. PEG-treated PNH patients experienced durable treatment effects in all efficacy parameters at Week 48 and the safety profile of PEG was consistent with previously reported data. The results suggest that PEG represents a new effective therapeutic option for PNH patients. |
| Author | Kiladjian, Jean-Jacques Höchsmann, Britta Usuki, Kensuke Risitano, Antonio Panse, Jens Röth, Alexander Weitz, Ilene Nishimori, Hisakazu Szer, Jeffrey Tan, Lisa Deschatelets, Pascal Griffin, Morag Grossi, Federico Hillmen, Peter de Castro, Carlos Francois, Cedric Al-Adhami, Mohammed de Latour, Régis Peffault |
| Author_xml | – sequence: 1 givenname: Régis Peffault surname: de Latour fullname: de Latour, Régis Peffault organization: French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Assistance Publique – Hôpitaux de Paris, Université de Paris, Paris, France, Paris, France – sequence: 2 givenname: Jeffrey surname: Szer fullname: Szer, Jeffrey organization: Department of Clinical Haematology, Royal Melbourne Hospital, Melbourne, VIC, Australia – sequence: 3 givenname: Ilene surname: Weitz fullname: Weitz, Ilene organization: Jane Anne Nohl Division of Hematology, Keck-USC School of Medicine, Los Angeles, CA, USA, United States – sequence: 4 givenname: Alexander surname: Röth fullname: Röth, Alexander organization: Department of Hematology and Stem Cell Transplantation, University Hospital Essen, University of Duisburg-Essen, Essen, Germany – sequence: 5 givenname: Britta surname: Höchsmann fullname: Höchsmann, Britta organization: University of Ulm and Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service and University Hospital Ulm, Institute of Transfusion Medicine, Ulm, Germany – sequence: 6 givenname: Jens surname: Panse fullname: Panse, Jens organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany – sequence: 7 givenname: Kensuke surname: Usuki fullname: Usuki, Kensuke organization: Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan – sequence: 8 givenname: Morag surname: Griffin fullname: Griffin, Morag organization: Department of Haematology, St James University Hospital, Leeds, United Kingdom – sequence: 9 givenname: Jean-Jacques surname: Kiladjian fullname: Kiladjian, Jean-Jacques organization: Centre d'Investigations Cliniques, Hôpital Saint-Louis; Assistance Publique – Hôpitaux de Paris; Université de Paris, Paris, France – sequence: 10 givenname: Carlos surname: de Castro fullname: de Castro, Carlos organization: Duke University School of Medicine, Durham, NC, USA, United States – sequence: 11 givenname: Hisakazu surname: Nishimori fullname: Nishimori, Hisakazu organization: Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan – sequence: 12 givenname: Lisa surname: Tan fullname: Tan, Lisa organization: Lisa Tan Pharma Consulting Ltd, Cambridge, United Kingdom – sequence: 13 givenname: Mohammed surname: Al-Adhami fullname: Al-Adhami, Mohammed organization: Apellis Pharmaceuticals, Inc., Waltham, MA, USA, United States – sequence: 14 givenname: Pascal surname: Deschatelets fullname: Deschatelets, Pascal organization: Apellis Pharmaceuticals, Inc., Waltham, MA, USA, United States – sequence: 15 givenname: Cedric surname: Francois fullname: Francois, Cedric organization: Apellis Pharmaceuticals, Inc., Waltham, MA, USA, United States – sequence: 16 givenname: Federico surname: Grossi fullname: Grossi, Federico organization: Apellis Pharmaceuticals, Inc., Waltham, MA, USA, United States – sequence: 17 givenname: Antonio surname: Risitano fullname: Risitano, Antonio organization: Hematology and BMT Unit, AORN San Giuseppe Moscati Avellino Italy, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy – sequence: 18 givenname: Peter surname: Hillmen fullname: Hillmen, Peter organization: Department of Haematology, St James University Hospital, Leeds, United Kingdom |
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| Snippet | Pegcetacoplan (PEG) is a C3 complement inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). PEG was superior to eculizumab (ECU;... |
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| Title | 3113 – FORTY-EIGHT WEEK EFFICACY AND SAFETY OF PEGCETACOPLAN IN ADULT PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA AND SUBOPTIMAL RESPONSE TO PRIOR ECULIZUMAB TREATMENT |
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