{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T02:49:04Z","timestamp":1786416544973,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Crovalimab is a novel C5 inhibitor administered first intravenously and then subcutaneously in patients with paroxysmal nocturnal haemoglobinuria (PNH) naive to complement inhibition or switching from eculizumab or ravulizumab. Crovalimab showed efficacy and safety comparable to eculizumab in the pivotal COMMODORE 2 and supporting studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We characterized crovalimab pharmacokinetics and the relationship between exposure pharmacokinetic parameters and pharmacodynamic biomarkers, efficacy and safety endpoints using pooled data (healthy volunteers [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099], naive [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009210] and switched [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009211] patients). Pharmacodynamic biomarkers included 50% complement activity and free C5; normalized lactate dehydrogenase was a marker of haemolysis. Adverse events (AEs) of special interest, related serious AEs, related Grade \u22653 AEs and infections were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There was no clinically relevant difference in crovalimab concentrations between naive and switch patients. Bodyweight had a statistically significant impact on crovalimab clearances and volumes of distribution. Thus, the recommended dosing regimen used weight\u2010based, two\u2010tiered dosing (100\u2009kg cutoff). Age did not have a clinically meaningful impact on crovalimab exposure. In COMMODORE 2, and the supporting COMMODORE 1 and 3 studies, complete terminal complement activity inhibition was achieved immediately at the end of the initial intravenous infusion and sustained throughout the treatment period in \u226597% of patients. Crovalimab concentrations above \u2248100\u2009\u03bcg\/mL achieved complete inhibition of terminal complement activity, resulting in disease control with normalized lactate dehydrogenase \u22641.5\u2009\u00d7\u2009upper limit of normal (ULN). There was no increased risk of AEs at higher exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data confirm an effective crovalimab\u2010dosing regimen that achieves complete terminal complement activity inhibition and disease control in patients with PNH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.16394","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T05:18:04Z","timestamp":1737436684000},"page":"1479-1490","source":"Crossref","is-referenced-by-count":10,"title":["Pharmacokinetic characterization and exposure\u2013response relationship of crovalimab in the COMMODORE 1, 2 and 3 and COMPOSER trials of patients with paroxysmal nocturnal haemoglobinuria"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7133-498X","authenticated-orcid":false,"given":"Val\u00e9rie","family":"Cosson","sequence":"first","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Hematology Tianjin Medical University General Hospital  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Kulasekararaj","sequence":"additional","affiliation":[{"name":"Department of Haematological Medicine King's College Hospital; National Institute for Health Research and Wellcome King's Clinical Research Facility and King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Ichi","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":"Alexander","family":"R\u00f6th","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Scheinberg","sequence":"additional","affiliation":[{"name":"Division of Hematology Hospital A Benefic\u00eancia Portuguesa  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Hematology, The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u2010Soo","family":"Yoon","sequence":"additional","affiliation":[{"name":"Clinical Research Institute Seoul National University Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Beveridge","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco CA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Gotanda","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9lix","family":"Jaminion","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0072-8352","authenticated-orcid":false,"given":"Andrea","family":"Henrich","sequence":"additional","affiliation":[{"name":"Pharmetheus AB  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontus","family":"Lundberg","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayu","family":"Shi","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha","family":"Sreckovic","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco CA United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2233-3063","authenticated-orcid":false,"given":"Yuchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Roche Innovation Centre  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Roche Product Development  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Benkali","sequence":"additional","affiliation":[{"name":"Certara, Inc.  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Buatois","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.28"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.093161"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201006\u2010094136"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201002\u2010522128"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01157"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201009\u2010876805"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201009\u2010876136"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061648"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010016\u20102867\u20108"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201001087\u20107"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1311084"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S233830"},{"key":"e_1_2_10_14_1","unstructured":"Genentech Inc.PIASKY [package insert].2024; South San Francisco CA USA."},{"key":"e_1_2_10_15_1","unstructured":"Chugai Pharmaceutical Co. Ltd.PIASKY [package insert].2024; Tokyo Japan."},{"key":"e_1_2_10_16_1","unstructured":"Chugai Pharmaceutical Co. Ltd.Crovalimab approved in China as the first country for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).https:\/\/www.chugai-pharm.co.jp\/english\/news\/detail\/20240208113000_1047.html?year=2024&category. Accessed August 1 2024."},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209509"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003399"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27413"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26998"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27412"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.14011"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/41.4.586"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12161"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2851"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2016.31.2.214"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010019\u201000742\u20108"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16711"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010021\u201001825\u20104"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010021\u201004715\u20105"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2023.29.8.941"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.16394","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T05:36:31Z","timestamp":1764740191000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.16394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,21]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/bcp.16394"],"URL":"https:\/\/doi.org\/10.1111\/bcp.16394","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,21]]}}}