{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T12:53:17Z","timestamp":1782305597009,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010795","name":"Chugai Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study reports long\u2010term outcomes from the open\u2010label extension (OLE) period of the Phase I\/II COMPOSER trial (NCT03157635) that evaluated crovalimab in patients with paroxysmal nocturnal haemoglobinuria, who were treatment\u2010naive or switched from eculizumab at enrolment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>COMPOSER consists of four sequential parts followed by the OLE. The primary OLE objective was to assess long\u2010term crovalimab safety, with a secondary objective to assess crovalimab pharmacokinetics and pharmacodynamics. Exploratory efficacy endpoints included change in lactate dehydrogenase (LDH), transfusion avoidance, haemoglobin stabilisation and breakthrough haemolysis (BTH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total 43 of 44 patients entered the OLE after completing the primary treatment period. Overall, 14 of 44 (32%) experienced treatment\u2010related adverse events. Steady state exposure levels of crovalimab and terminal complement inhibition were maintained over the OLE. During the OLE, mean normalised LDH was generally maintained at \u22641.5\u00d7 upper limit of normal, transfusion avoidance was achieved in 83%\u201392% of patients and haemoglobin stabilisation was reached in 79%\u201388% of patients across each 24\u2010week interval. Five BTH events occurred with none leading to withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Over a 3\u2010year median treatment duration, crovalimab was well tolerated and sustained C5 inhibition was achieved. Intravascular haemolysis control, haemoglobin stabilisation and transfusion avoidance were maintained, signifying long\u2010term crovalimab efficacy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.14011","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:25:25Z","timestamp":1686875125000},"page":"300-310","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Crovalimab treatment in patients with paroxysmal nocturnal haemoglobinuria: Long\u2010term results from the phase I\/II COMPOSER trial"],"prefix":"10.1111","volume":"111","author":[{"given":"Alexander","family":"R\u00f6th","sequence":"first","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen University Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Hematology Tohoku University Hospital  Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Hematology Tokyo Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":"Zsolt","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Hematology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoshi","family":"Obara","sequence":"additional","affiliation":[{"name":"Department of Hematology, Faculty of Medicine University of Tsukuba  Ibaraki Japan"}],"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), Aachen, Bonn, Cologne, D\u00fcsseldorf (ABCD)  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Schrezenmeier","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine and Immunogenetics Ulm German Red Cross Blood Transfusion Service Baden\u2010W\u00fcrttemberg\u2010Hessen und University Hospital Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Sica","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS Universit\u00e0 Cattolica Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Soret","sequence":"additional","affiliation":[{"name":"Centre d'Investigations Cliniques H\u00f4pital Saint\u2010Louis  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Usuki","sequence":"additional","affiliation":[{"name":"Department of Hematology NTT Medical Center Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u2010Soo","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Seoul National University Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadiesh","family":"Balachandran","sequence":"additional","affiliation":[{"name":"Portfolio Clinical Safety F. 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Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Sostelly","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology F. 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