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COMMODORE 1 (NCT04432584) is a phase 3, global, randomized trial evaluating crovalimab versus eculizumab in C5 inhibitor\u2010experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). Adults with lactate dehydrogenase \u22641.5\u2009\u00d7\u2009upper limit of normal and receiving approved eculizumab doses for \u226524\u2009weeks were randomized 1:1 to receive crovalimab (weight\u2010based 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\u2010Fatigue score, and patient preference (crovalimab vs. eculizumab). Eighty\u2010nine patients were randomized (45 to crovalimab; 44 to eculizumab). During the 24\u2010week 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\u2010treated 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\u2010treated 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\u2010naive patients, these data support crovalimab's favorable benefit\u2013risk profile. Crovalimab is a new C5 inhibitor for PNH that is potentially less burdensome than existing therapies for this lifelong disease.<\/jats:p>","DOI":"10.1002\/ajh.27413","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T06:09:46Z","timestamp":1719382186000},"page":"1757-1767","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor\u2010experienced patients with paroxysmal nocturnal hemoglobinuria"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9047-4538","authenticated-orcid":false,"given":"Phillip","family":"Scheinberg","sequence":"first","affiliation":[{"name":"Division of Hematology Hospital A Benefic\u00eancia Portuguesa  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Villa","family":"Cl\u00e9","sequence":"additional","affiliation":[{"name":"Ribeir\u00e3o Preto School of Medicine University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8986-8436","authenticated-orcid":false,"given":"Jin Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Yonsei University College of Medicine Severance Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erfan","family":"Nur","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Blood Cell Research Sanquin Research  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa N.","family":"Yenerel","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine Istanbul University, Istanbul Faculty of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-9944","authenticated-orcid":false,"given":"Wilma","family":"Barcellini","sequence":"additional","affiliation":[{"name":"Hematology Unit Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Bonito","sequence":"additional","affiliation":[{"name":"CEPHO\/Faculty of Medicine of ABC  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Giai","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology AOU Citt\u00e0 della Salute e della Scienza di Torino  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Hus","sequence":"additional","affiliation":[{"name":"Department of Hemato Oncology and Bone Marrow Transplantation Medical University of Lublin  Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YooJin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Ulsan University Hospital University of Ulsan College of Medicine  Ulsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Barrenetxea","family":"Lekue","sequence":"additional","affiliation":[{"name":"Department of Hematology Hospital Universitario de Basurto  Bilbao Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6316-3112","authenticated-orcid":false,"given":"Jens","family":"Panse","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology Hemostaseology and Stem Cell Transplantation University Hospital RWTH Aachen  Aachen Germany"},{"name":"Centre for Integrated Oncology (CIO)  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Graduate School of Medicine, Faculty of Medicine Osaka University  Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Buatois","sequence":"additional","affiliation":[{"name":"F. 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