{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:06:47Z","timestamp":1784300807963,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Valoctocogene roxaparvovec is an adeno\u2010associated virus vector serotype 5 (AAV5)\u2010mediated gene therapy for severe haemophilia A (HA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Report the final safety and efficacy results of the phase 1\/2 trial of valoctocogene roxaparvovec.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An open\u2010label phase 1\/2 trial (NCT02576795) enrolled adult males with severe HA (factor VIII [FVIII] \u22641\u00a0IU\/dL) without FVIII inhibitors, anti\u2010AAV5 antibodies, or liver dysfunction to receive 6\u00a0\u00d7\u00a010\n                      <jats:sup>13<\/jats:sup>\n                      or 4\u00a0\u00d7\u00a010\n                      <jats:sup>13<\/jats:sup>\n                      vg\/kg valoctocogene roxaparvovec. Efficacy endpoints included FVIII activity (chromogenic), annualized bleeding rate (ABR) of treated bleeds, annualized FVIII infusion rate, and quality of life. Safety was assessed by adverse events (AEs). Year seven 6\u00a0\u00d7\u00a010\n                      <jats:sup>13<\/jats:sup>\n                      vg\/kg cohort results were reported previously.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five of six 4\u00a0\u00d7\u00a010\n                      <jats:sup>13<\/jats:sup>\n                      vg\/kg cohort participants completed the 7\u2010year study. Mean FVIII activity peaked within year 1 for the 4\u00a0\u00d7\u00a010\n                      <jats:sup>13<\/jats:sup>\n                      cohort (week 52 FVIII, 21.1\u00a0IU\/dL) and decreased to 4.2\u00a0IU\/dL at the end of year 7. Across all follow\u2010up, mean ABR declined 87% from baseline to 1.6 bleeds\/year and mean annualized FVIII use declined 93% to 10.3 infusions\/year. Overall, 3\/5 of the 4\u00a0\u00d7\u00a010\n                      <jats:sup>13<\/jats:sup>\n                      participants remain off prophylaxis. Haemo\u2010QOL\u2010A Total Score was mostly stable from baseline. The last treatment\u2010related AE (TRAE) of alanine aminotransferase elevation occurred in year 1. No serious TRAEs occurred after year 1. No participants had thromboembolic events or developed FVIII inhibitors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Over 7 years, valoctocogene roxaparvovec increased FVIII activity from baseline and improved haemostasis compared with FVIII prophylaxis for most participants. The 6\u00a0\u00d7\u00a010\n                      <jats:sup>13<\/jats:sup>\n                      vg\/kg dose was more efficacious than 4\u00a0\u00d7\u00a010\n                      <jats:sup>13<\/jats:sup>\n                      vg\/kg. No concerning long\u2010term safety signals were identified.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.70284","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:21:52Z","timestamp":1776054112000},"page":"974-981","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Final Analysis of the Phase 1\/2 Trial of Valoctocogene Roxaparvovec for Severe Haemophilia A"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6365-2899","authenticated-orcid":false,"given":"Priyanka","family":"Raheja","sequence":"first","affiliation":[{"name":"Haemophilia Centre Barts Health NHS Trust, The Royal London Hospital  London 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":"University Hospitals Birmingham NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Madan","sequence":"additional","affiliation":[{"name":"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  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2529-8168","authenticated-orcid":false,"given":"Emily","family":"Symington","sequence":"additional","affiliation":[{"name":"Haemophilia Centre Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Millar","sequence":"additional","affiliation":[{"name":"Imperial College Healthcare NHS Trust\u00a0and\u00a0Centre for Haematology, Department of Immunology and Inflammation Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane","family":"Osmond","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc.  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