{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T12:32:54Z","timestamp":1793795574077,"version":"4.6.1"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Valoctocogene roxaparvovec is an adeno\u2010associated virus vector serotype 5 (AAV5)\u2010mediated gene therapy approved for severe haemophilia A (HA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To report the safety and efficacy of valoctocogene roxaparvovec 7 years after dosing in a phase 1\/2 clinical study (NCT02576795).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Males \u226518 years with severe HA (factor VIII [FVIII] \u22641 international unit [IU]\/dL) who were previously receiving exogenous FVIII and had no history of FVIII inhibitors or anti\u2010AAV5 antibodies received valoctocogene roxaparvovec treatment and were followed for 7 (6\u00a0\u00d7\u00a010<jats:sup>13<\/jats:sup>\u00a0vg\/kg; <jats:italic>n<\/jats:italic>\u00a0=\u00a07) and 6 (4\u00a0\u00d7\u00a010<jats:sup>13<\/jats:sup>\u00a0vg\/kg; <jats:italic>n<\/jats:italic>\u00a0=\u00a06) years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the last year, one participant in each cohort reported treatment\u2010related adverse events (AEs): grade 1 (G1) hepatomegaly (6\u00a0\u00d7\u00a010<jats:sup>13<\/jats:sup>), and G1 splenomegaly and G1 hepatic steatosis (4\u00a0\u00d7\u00a010<jats:sup>13<\/jats:sup>). During all follow\u2010up, mean annualized treated bleeds and exogenous FVIII infusion rates were \u226588% lower than baseline values. At years 7 and 6, mean (median) FVIII activity (chromogenic assay) was 16.2 (10.3) and 6.7 (7.2) IU\/dL in the 6\u00a0\u00d7\u00a010<jats:sup>13<\/jats:sup> (<jats:italic>n<\/jats:italic>\u00a0=\u00a05) and 4\u00a0\u00d7\u00a010<jats:sup>13<\/jats:sup> (<jats:italic>n<\/jats:italic>\u00a0=\u00a04) cohorts, respectively, corresponding to mild haemophilia. Regression analyses of the last year estimated rate of change in FVIII activity was \u20100.001 and \u20100.07\u00a0IU\/dL\/week for the 6\u00a0\u00d7\u00a010<jats:sup>13<\/jats:sup> and 4\u00a0\u00d7\u00a010<jats:sup>13<\/jats:sup> cohorts, respectively. Two participants (6\u00a0\u00d7\u00a010<jats:sup>13<\/jats:sup>) resumed prophylaxis in year 7: one after a non\u2010treatment\u2010related G4 serious AE of spontaneous internal carotid artery bleed, and the other to manage bleeds and FVIII activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The safety and efficacy of valoctocogene roxaparvovec remain generally consistent with previous reports, with good haemostatic control for most participants. Two participants returned to prophylaxis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.15071","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T11:40:56Z","timestamp":1720438856000},"page":"1138-1147","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Valoctocogene roxaparvovec gene therapy provides durable haemostatic control for up to 7 years for haemophilia A"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2529-8168","authenticated-orcid":false,"given":"Emily","family":"Symington","sequence":"first","affiliation":[{"name":"Haemophilia Centre Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savita","family":"Rangarajan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8790-7112","authenticated-orcid":false,"given":"Will","family":"Lester","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences University Hospitals Birmingham NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Madan","sequence":"additional","affiliation":[{"name":"Centre for Haemostasis and Thrombosis Guy's and St Thomas\u2019 NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3310-328X","authenticated-orcid":false,"given":"Glenn F.","family":"Pierce","sequence":"additional","affiliation":[{"name":"Independent Consultant  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Raheja","sequence":"additional","affiliation":[{"name":"The Royal London Hospital Haemophilia Centre Barts Health NHS Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Millar","sequence":"additional","affiliation":[{"name":"Department of Immunology and Inflammation Imperial College Healthcare NHS Trust and Centre for Haematology Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane","family":"Osmond","sequence":"additional","affiliation":[{"name":"Clinical sciences BioMarin Pharmaceutical Inc  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjin","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical sciences BioMarin Pharmaceutical Inc  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara M.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Clinical sciences BioMarin Pharmaceutical Inc  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2019.03.002"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009217"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12567"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14807"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708483"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908490"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14391"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14936"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2113708"},{"key":"e_1_2_11_12_1","unstructured":"First gene therapy for adults with severe hemophilia A BioMarin's ROCTAVIAN\u2122 (valoctocogene roxaparvovec) approved by European Commission (EC).BioMarin Pharmaceutical Inc.; August 24 2022. 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