{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T16:54:42Z","timestamp":1781542482468,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"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":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Valoctocogene roxaparvovec, a gene therapy evaluated in the phase 3 GENEr8\u20101 trial, supports endogenous factor VIII (FVIII) production to prevent bleeding in people with severe haemophilia A. Individuals receiving emicizumab, an antibody mimicking the function of activated FVIII, were excluded from GENEr8\u20101 enrolment since emicizumab was an investigational therapy at the time of trial initiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>Utilize pharmacokinetic simulations to provide guidance on best practices for maintaining haemostatic control while transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To estimate bleeding risk at weekly intervals following valoctocogene roxaparvovec infusion, a published emicizumab pharmacokinetic model was used to simulate emicizumab concentrations and merged with FVIII activity time\u2010course data for participants in GENEr8\u20101. The analysis investigated three approved emicizumab dosing regimens for two transition scenarios that varied whether the last dose of emicizumab was administered on the same day or 4\u00a0weeks after valoctocogene roxaparvovec infusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Simulations demonstrated administering the last emicizumab dose the day of valoctocogene roxaparvovec infusion and 4\u00a0weeks after offered similar levels of haemostatic control, and bleeding risk was similar for all emicizumab dosing regimens. An algorithm was developed to provide guidance for discontinuation of emicizumab. Theoretical cases based on GENEr8\u20101 participants are presented to illustrate how decisions may vary among individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Pharmacokinetic simulations demonstrated no clinically meaningful difference in bleeding risk caused by decaying emicizumab levels and rising gene therapy\u2010derived endogenous FVIII for all examined emicizumab doses and dosing regimens. Therefore, multiple approaches can safely transition individuals from emicizumab prophylaxis to valoctocogene roxaparvovec.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.15025","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T02:28:30Z","timestamp":1714444110000},"page":"905-913","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec gene therapy: A simulation study for individuals with severe haemophilia A"],"prefix":"10.1111","volume":"30","author":[{"given":"Suresh","family":"Agarwal","sequence":"first","affiliation":[{"name":"BioMarin Pharmaceutical Inc.  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Hermans","sequence":"additional","affiliation":[{"name":"Division of Adult Haematology Cliniques universitaires Saint\u2010Luc Universit\u00e9 catholique de Louvain (UCLouvain)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4506-0061","authenticated-orcid":false,"given":"Wolfgang","family":"Miesbach","sequence":"additional","affiliation":[{"name":"Medical Clinic 2 University Hospital Frankfurt  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-9864","authenticated-orcid":false,"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa  Milan Italy"},{"name":"Department of Pathophysiology and Transplantation Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9509-9415","authenticated-orcid":false,"suffix":"Jr","given":"Robert","family":"Sidonio","sequence":"additional","affiliation":[{"name":"Hemostasis and Thrombosis Program Children's Healthcare of Atlanta Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane","family":"Osmond","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc.  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Newman","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc.  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Henshaw","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc.  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2558-2089","authenticated-orcid":false,"given":"Steven","family":"Pipe","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Pathology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10245959"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13449"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803550"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009217"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2942"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057479"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-06-650226"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12474"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1703068"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001869"},{"key":"e_1_2_10_13_1","unstructured":"European Medicines Agency.Assessment report: Hemlibra (international non\u2010proprietary name: emicizumab).2018.https:\/\/www.ema.europa.eu\/en\/documents\/assessment\u2010report\/hemlibra\u2010epar\u2010public\u2010assessment\u2010report_en.pdf"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1511769"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14769"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14372"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14524"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.09.020"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-022-01788-y"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2113708"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908490"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708483"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00904-z"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30054-7"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01006-0"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02383.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14483"},{"issue":"2","key":"e_1_2_10_28_1","article-title":"Efficacy of reduced\u2010dose emicizumab in haemophilia A with inhibitors: real world experience in East Malaysia [abstract]","volume":"5","author":"Tang ASO","year":"2021","journal-title":"Res Pract Thromb Haemost"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018020552"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1688687"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13903"},{"key":"e_1_2_10_32_1","unstructured":"National Bleeding Disorders Foundation.MASAC document 258\u2010recommendation on the use and management of emicizumab\u2010kxwh (Hemlibra\u00ae) for hemophilia A with and without inhibitors. 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