Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor‐experienced patients with paroxysmal nocturnal hemoglobinuria
American Journal of Hematology, vol. 99, pp. 1757–1767
Abstract
Crovalimab, a novel C5 inhibitor, allows for low-volume, every-4- week, subcutaneous self-administration. COMMODORE 1 (NCT04432584) is a phase 3, global, randomized trial evaluating crovalimab versus eculizumab in C5 inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). Adults with lactate dehydrogenase ≤1.5 × upper limit of normal and receiving approved eculizumab doses for ≥24 weeks were randomized 1:1 to receive crovalimab (weight-based tiered dosing) or continue eculizumab. The original primary study objective was efficacy; however, given the evolving treatment landscape, target recruitment was not met, and all efficacy endpoints became exploratory, with safety as the new primary objective. Exploratory efficacy endpoints included transfusion avoidance, hemolysis control, breakthrough hemolysis, hemoglobin stabilization, FACIT-Fatigue score, and patient preference (crovalimab vs. eculizumab). Eighty-nine patients were randomized (45 to crovalimab; 44 to eculizumab). During the 24-week primary treatment period, adverse events (AEs) occurred in 77% of patients receiving crovalimab and 67% receiving eculizumab. No AEs led to treatment withdrawal or death, and no meningococcal infections occurred. 16% of crovalimab-treated patients had transient immune complex reactions (also known as Type III hypersensitivity events), an expected risk when switching between C5 inhibitors that bind to different C5 epitopes; most were mild/moderate and all resolved without treatment modification. Crovalimab-treated patients had sustained terminal complement activity inhibition, maintained disease control, and 85% preferred crovalimab over eculizumab. Together with phase 3 COMMODORE 2 results in complement inhibitor-naive patients, these data support crovalimab's favorable benefit-risk profile. Crovalimab is a new C5 inhibitor for PNH that is potentially less burdensome than existing therapies for this lifelong disease.
Authors 21
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Phillip Scheinberg corresponding
Beneficência Portuguesa de São Paulo
Affiliation as printed
Division of Hematology Hospital A Beneficência Portuguesa São Paulo Brazil
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Affiliation as printed
Ribeirão Preto School of Medicine University of São Paulo Ribeirão Preto Brazil
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Yonsei University · Severance Hospital
Affiliation as printed
Yonsei University College of Medicine Severance Hospital Seoul South Korea
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Amsterdam UMC Location University of Amsterdam · Sanquin · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Blood Cell Research Sanquin Research Amsterdam The Netherlands
Department of Hematology, Amsterdam UMC University of Amsterdam Amsterdam The Netherlands
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Affiliation as printed
Division of Hematology, Department of Internal Medicine Istanbul University, Istanbul Faculty of Medicine Istanbul Turkey
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Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Affiliation as printed
Hematology Unit Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy
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Affiliation as printed
CEPHO/Faculty of Medicine of ABC São Paulo Brazil
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Azienda Ospedaliera Citta' della Salute e della Scienza di Torino
Affiliation as printed
Department of Hematology and Oncology AOU Città della Salute e della Scienza di Torino Turin Italy
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Affiliation as printed
Department of Hemato Oncology and Bone Marrow Transplantation Medical University of Lublin Lublin Poland
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University of Ulsan · Ulsan University Hospital
Affiliation as printed
Department of Hematology and Oncology, Ulsan University Hospital University of Ulsan College of Medicine Ulsan Republic of Korea
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Affiliation as printed
Department of Hematology Hospital Universitario de Basurto Bilbao Spain
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Centre for Integrated Oncology (CIO) Cologne Germany
Department of Oncology, Hematology Hemostaseology and Stem Cell Transplantation University Hospital RWTH Aachen Aachen Germany
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Affiliation as printed
Department of Hematology and Oncology, Graduate School of Medicine, Faculty of Medicine Osaka University Suita Japan
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Affiliation as printed
F. Hoffmann‐La Roche Ltd Basel Switzerland
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Affiliation as printed
Genentech, Inc. South San Francisco California USA
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Affiliation as printed
F. Hoffmann‐La Roche Ltd Basel Switzerland
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Affiliation as printed
Genentech, Inc. South San Francisco California USA
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Affiliation as printed
Genentech, Inc. South San Francisco California USA
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Affiliation as printed
F. Hoffmann‐La Roche Ltd Basel Switzerland
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Affiliation as printed
Department of Internal Medicine and Hematology Semmelweis University Budapest Hungary
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King's College London · National Institute for Health and Care Research · King's College Hospital
Affiliation as printed
Department of Haematological Medicine King's College Hospital London UK
National Institute for Health Research and Wellcome King's Clinical Research Facility and King's College London London UK
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