{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:48:13Z","timestamp":1788875293452,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008484","name":"BioMarin Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pericles.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Head\u2010to\u2010head evaluation of valoctocogene roxaparvovec, the first gene therapy approved for haemophilia A, with emicizumab is not available. Therefore, phase 3 trial data were indirectly compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To compare bleeding rates in trials evaluating 6\u00a0\u00d7\u00a010<jats:sup>13<\/jats:sup>\u00a0vg\/kg valoctocogene roxaparvovec (GENEr8\u20101; NCT03370913), 1.5\u00a0mg\/kg emicizumab dosed every week (HAVEN 3; NCT02847637), and FVIII prophylaxis (270\u2013902) in participants with severe haemophilia A (FVIII \u22641\u00a0IU\/dL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Valoctocogene roxaparvovec versus emicizumab and FVIII prophylaxis as used in 270\u2013902\u00a0versus emicizumab cross\u2010trial comparisons were performed using matching\u2010adjusted indirect comparison (MAIC). Individual participant data from GENEr8\u20101 and 270\u2013902 were weighted to equalise aggregate participant baseline characteristics from HAVEN 3. After MAIC weighting, annualised bleeding rates (ABR) and proportions of participants without bleeds were compared for treated bleeds, all bleeds, treated joint bleeds, and treated spontaneous bleeds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After MAIC weighting, ABR for all bleeds was statistically significantly lower with valoctocogene roxaparvovec than emicizumab (rate ratio [95% CI], .55 [.33\u2013.93]). Additionally, significantly higher proportions of participants had no treated joint bleeds (odds ratio [95% CI], 2.75 [1.20\u20136.31]) and no treated bleeds (3.25 [1.53\u20136.90]) with valoctocogene roxaparvovec versus emicizumab. When compared with the mainly standard half\u2010life FVIII prophylaxis regimens in 270\u2013902, mean ABRs (except for all bleeds) were significantly lower, and significantly higher proportions reported 0 bleeds for all outcomes with emicizumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Valoctocogene roxaparvovec provided generally lower bleeding rates and higher probability of no bleeds, including treated joint bleeds, than emicizumab. Emicizumab was more effective than FVIII prophylaxis regimens used in 270\u2013902.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14818","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T21:35:06Z","timestamp":1687642506000},"page":"1087-1094","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Matching\u2010adjusted indirect comparison of bleeding outcomes in severe haemophilia A: Comparing valoctocogene roxaparvovec gene therapy, emicizumab prophylaxis, and FVIII replacement prophylaxis"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-2483","authenticated-orcid":false,"given":"Jan","family":"Astermark","sequence":"first","affiliation":[{"name":"Department of Translational Medicine Lund University Lund Sweden"},{"name":"Department for Hematology Oncology and Radiation Physics, Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler W","family":"Buckner","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine Hemophilia and Thrombosis Center Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6085-2163","authenticated-orcid":false,"given":"Laurent","family":"Frenzel","sequence":"additional","affiliation":[{"name":"Centre de Traitement de l'Hemophilie, AP\u2010HP, H\u00f4pital Universitaire Necker\u2010Enfants Malades Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Hatswell","sequence":"additional","affiliation":[{"name":"Delta Hat Limited Nottingham UK"},{"name":"Department of Statistics University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"You","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc. Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Liu","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc. Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Goodman","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc. Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Santos","sequence":"additional","affiliation":[{"name":"BioMarin UK Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Hawes","sequence":"additional","affiliation":[{"name":"BioMarin UK Ltd London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hinds","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc. Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4194-8183","authenticated-orcid":false,"given":"Robert","family":"Klamroth","sequence":"additional","affiliation":[{"name":"Vascular Medicine and Haemostaseology, Vivantes Klinikum im Friedrichshain Berlin Germany"},{"name":"Institute of Experimental Hematology and Transfusion Medicine University Hospital Bonn, Medical Faculty, University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13449"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24220"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009217"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803550"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2022.2105072"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2019.1649378"},{"key":"e_1_2_11_9_1","first-page":"1687","article-title":"Patient and parent preferences for characteristics of prophylactic treatment in hemophilia","volume":"9","author":"Furlan R","year":"2015","journal-title":"Patient Prefer Adherence"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14304"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40271-019-00395-6"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.12.009"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01751-0"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708483"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908490"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14391"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2113708"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10245959"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211075"},{"key":"e_1_2_11_20_1","article-title":"A randomized, multicenter, open\u2010label, phase III clinical trial to evaluate the efficacy, safety, and pharmacokinetics of prophylactic emicizumab versus no prophylaxis in hemophilia A patients without inhibitors (clinical trial registration No. NCT02847637)","author":"Hoffman\u2010La Roche","journal-title":"ClinicalTrialsgov"},{"key":"e_1_2_11_21_1","unstructured":"European Medicines Agency.Assessment Report. 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