{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:10:28Z","timestamp":1789413028464,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T00:00:00Z","timestamp":1742688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Efanesoctocog alfa is a first\u2010in\u2010class high\u2010sustained factor VIII (HSF) replacement therapy for treatment of hemophilia A. This article presents population pharmacokinetics (PopPK) of efanesoctocog alfa and repeated time\u2010to\u2010event (RTTE) analysis of bleeding episodes in adults\/adolescents (\u226512 years of age) and children (&lt;12 years). The final PopPK dataset contained pooled data from 277 patients (4405 post\u2010dose factor VIII [FVIII] activity records) from two Phase 1\/2a studies (NCT03205163; EudraCT 2018\u2010001535\u201051), and three Phase 3 studies, XTEND\u20101 (NCT04161495), XTEND\u2010Kids (NCT04759131), and XTEND\u2010ed (NCT04644575). The PopPK model developed was a linear one\u2010compartment model including body weight effect on clearance and volume of central compartment; Asian race was identified as a statistically significant covariate on clearance. The final PopPK model adequately described the FVIII activity\u2013time profiles in adults, adolescents, and children with once\u2010weekly (QW) efanesoctocog alfa 50 IU\/kg, consistent with experience in XTEND\u20101 and XTEND\u2010Kids. Bleeding episodes in participants in XTEND\u20101 and XTEND\u2010Kids were characterized by an RTTE model with a Weibull base hazard and effect of FVIII activity modeled by a power effect. The RTTE model showed the probability of being bleed\u2010free in 1 year with efanesoctocog alfa 50 IU\/kg QW regimen was &gt;70% across all age groups, consistent with the observed clinical outcomes in the Phase 3 trials of highly effective protection from bleeding episodes in patients with severe hemophilia A, which validates the model's prediction of the long\u2010term bleed hazard.<\/jats:p>","DOI":"10.1002\/jcph.70008","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T08:40:56Z","timestamp":1742805656000},"page":"860-872","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Efanesoctocog Alfa Population Pharmacokinetics and Repeated Time\u2010To\u2010Event Analysis of Bleeds in Adults, Adolescents, and Children with Severe Hemophilia A"],"prefix":"10.1002","volume":"65","author":[{"given":"Nancy","family":"Wong","sequence":"first","affiliation":[{"name":"Sanofi  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8740-2705","authenticated-orcid":false,"given":"Pratik","family":"Bhagunde","sequence":"additional","affiliation":[{"name":"Sanofi  Bridgewater NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joakim","family":"Nyberg","sequence":"additional","affiliation":[{"name":"Pharmetheus AB  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Katragadda","sequence":"additional","affiliation":[{"name":"Sanofi  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Demissie","sequence":"additional","affiliation":[{"name":"Sanofi  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Willemze","sequence":"additional","affiliation":[{"name":"Sanofi  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Benson","sequence":"additional","affiliation":[{"name":"Sanofi  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreeraj","family":"Macha","sequence":"additional","affiliation":[{"name":"Sanofi  Bridgewater NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_12_3_1","article-title":"Optimising prophylaxis in haemophilia A: The ups and downs of treatment","author":"Berntorp E","year":"2021","journal-title":"Blood Rev"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14201"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005673"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14866"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001292"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2002699"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12076"},{"key":"e_1_2_12_10_1","first-page":"24052","article-title":"Extension of in vivo half\u2010life of biologically active molecules by XTEN protein polymers","author":"Podust VN","year":"2016","journal-title":"J Control Release"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021006119"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2023.100176"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2209226"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12672"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312611"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1598058"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14831"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024012862"},{"key":"e_1_2_12_19_1","volume-title":"ALTUVIIIO United States Prescribing Information","author":"Bioverativ Therapeutics Inc","year":"2023"},{"key":"e_1_2_12_20_1","volume-title":"A repeated time\u2010to\u2010event model is superior to a count regression analysis in linking FVIII activity to bleeding events in prophylactically treated patients with severe haemophilia. Population Approach Group Europe","author":"Gentsch GSA","year":"2018"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.217133"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12938"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T01:57:26Z","timestamp":1750989446000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,23]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/jcph.70008"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70008","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,23]]},"assertion":[{"value":"2024-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}