Plain Language Summary of PEGASUS, a Study Comparing Pegcetacoplan with Eculizumab for 16 Weeks in People with Paroxysmal Nocturnal Hemoglobinuria
Future Rare Diseases, vol. 3
Abstract
What is this summary about? This plain language summary is about a phase 3 clinical trial called PEGASUS. The PEGASUS trial studied adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder usually acquired in adulthood without a known cause. Patients with PNH have defects in the complement system, which is part of the immune defense system. This complement defect results in the destruction of red blood cells; this is called hemolysis. Hemolysis then causes anemia. People with anemia do not have enough red blood cells to carry oxygen around the body, which can cause fatigue (extreme tiredness), shortness of breath, or headache. Anemia can be measured by the level or amount of hemoglobin in the blood. Hemolysis can be measured by the amount of hemoglobin, lactate dehydrogenase (LDH), and reticulocytes in the blood. Hemoglobin and LDH are proteins inside red blood cells. In patients with PNH, hemolysis causes hemoglobin levels to go down and LDH levels go up. Reticulocytes are immature red blood cells; their level goes up during hemolysis to replace destroyed red blood cells. Eculizumab is the current standard of care for patients with PNH. Eculizumab is a medicine that blocks or inhibits the complement component 5 (C5). Pegcetacoplan is a new medicine, the first that inhibits the complement component C3. The PEGASUS study compared the new medicine pegcetacoplan with eculizumab in adults with PNH who remained anemic even after being treated with eculizumab for at least 3 months. In PEGASUS, 41 participants received pegcetacoplan and 39 people received eculizumab for 16 weeks. What were the results? The trial results showed that pegcetacoplan decreased signs of hemolysis compared to eculizumab. Participants treated with pegcetacoplan for 16 weeks had increased blood levels of hemoglobin, and decreased levels of LDH and reticulocytes; also, 85% of them no longer needed a blood transfusion compared with 15% of those treated with eculizumab. A patient survey showed that 73% of patients who received pegcetacoplan had decreased fatigue. None of the participants treated with eculizumab had decreased fatigue. Most participants in both treatment groups had side effects. However, no serious infections or thrombosis (blood clots) occurred with either treatment group. Episodes of hemolysis during treatment, called breakthrough hemolysis, happened in 10% of pegcetacoplan- and 23% of eculizumab-treated participants. What do the results mean? Pegcetacoplan reduced the level of hemolysis in adults with PNH better than eculizumab did. Pegcetacoplan was well tolerated by most patients in this study.
Authors 17
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St James's University Hospital
Affiliation as printed
Department of Haematology, St. James’s University Hospital
Department of Haematology, St. James's University Hospital, Leeds, UK
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The Royal Melbourne Hospital · Peter MacCallum Cancer Centre
Affiliation as printed
Department of Clinical Haematology, Peter MacCallum Cancer Center & Royal Melbourne Hospital
Department of Clinical Haematology, Peter MacCallum Cancer Center & Royal Melbourne Hospital, Melbourne, VIC, Australia
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University of Southern California
Affiliation as printed
Jane Anne Nohl Division of Hematology, Keck School of Medicine of USC
Jane Anne Nohl Division of Hematology, Keck School of Medicine of USC, Los Angeles, USA
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Essen University Hospital · University of Duisburg-Essen
Affiliation as printed
Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen
Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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Universität Ulm · German Red Cross · University Hospital Ulm
Affiliation as printed
German Red Cross Blood Transfusion Service & University Hospital Ulm
Institute of Transfusion Medicine
University of Ulm & Institute of Clinical Transfusion Medicine & Immunogenetics
Institute of Transfusion Medicine, University of Ulm & Institute of Clinical Transfusion Medicine & Immunogenetics, German Red Cross Blood Transfusion Service & University Hospital Ulm, Ulm, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Oncology, Hematology, Hemostaseology & Stem Cell Transplantation, University Hospital RWTH Aachen
Department of Oncology, Hematology, Hemostaseology & Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany
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Affiliation as printed
Department of Hematology, NTT Medical Center Tokyo
Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan
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St James's University Hospital
Affiliation as printed
Department of Haematology, St. James’s University Hospital
Department of Haematology, St. James's University Hospital, Leeds, UK
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Affiliation as printed
Centre d’Investigations Cliniques
Centre d'Investigations Cliniques, Paris, France
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Affiliation as printed
Department of Hematology & Oncology, Okayama University Hospital
Department of Hematology & Oncology, Okayama University Hospital, Okayama, Japan
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Affiliation as printed
Lisa Tan Pharma Consulting
Lisa Tan Pharma Consulting, Cambridge, UK
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Apellis Pharmaceuticals (United States)
Affiliation as printed
Apellis Pharmaceuticals
Apellis Pharmaceuticals, Waltham, MA, USA
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Apellis Pharmaceuticals (United States)
Affiliation as printed
Apellis Pharmaceuticals
Apellis Pharmaceuticals, Waltham, MA, USA
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Apellis Pharmaceuticals (United States)
Affiliation as printed
Apellis Pharmaceuticals
Apellis Pharmaceuticals, Waltham, MA, USA
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Apellis Pharmaceuticals (United States)
Affiliation as printed
Apellis Pharmaceuticals
Apellis Pharmaceuticals, Waltham, MA, USA
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Azienda Ospedaliera S.Giuseppe Moscati
Affiliation as printed
Hematology & BMT Unit, AORN San Giuseppe Moscati
Hematology & BMT Unit, AORN San Giuseppe Moscati, Avellino, Italy
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Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Hôpital Saint-Louis
Affiliation as printed
French Reference Center for Aplastic Anemia & Paroxysmal Nocturnal Hemoglobinuria, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris, Université de Paris
French Reference Center for Aplastic Anemia & Paroxysmal Nocturnal Hemoglobinuria, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris, Université de Paris, Paris, France
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