{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T12:19:20Z","timestamp":1753359560182,"version":"3.40.5"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:p>Marzeptacog alfa (MarzAA) is under development for subcutaneous treatment of episodic bleeds in patients with hemophilia A\/B and was studied in a phase III trial evaluating MarzAA compared with standard\u2010of\u2010care (SoC) for on\u2010demand use. The work presented here aimed to evaluate MarzAA and SoC treatment of bleeding events on a standardized four\u2010point efficacy scale (poor, fair, good, and excellent). Two continuous\u2010time Markov modeling approaches were explored; a four\u2010state model analyzing all four categories of bleeding improvement and a two\u2010state model analyzing a binarized outcome (treatment failure (poor\/fair), and treatment success (good\/excellent)). Different covariates impacting improvement of bleeding episodes as well as a putative relationship between MarzAA exposure and improvement of bleeding episodes were evaluated. In the final four\u2010state model, higher baseline diastolic blood pressure and higher age (&gt;\u200933\u2009years of age) were found to negatively and positively impact improvement of bleeding condition, respectively. Bleeding events occurring in knees and ankles were found to improve faster than bleeding events at other locations. The covariate effects had most impact on early treatment success (\u2264\u20093\u2009hours) whereas at later timepoints (&gt;\u200912\u2009hours), treatment success was similar for all patients indicating that these covariates might be clinically relevant for early treatment response. A statistically significant relationship between MarzAA zero\u2010order absorption and improvement of bleedings (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) were identified albeit with low precision. No statistically significant difference in treatment response between MarzAA and intravenous SoC was identified, indicating the potential of MarzAA for treatment of episodic bleeding events with a favorable subcutaneous administration route.<\/jats:p>","DOI":"10.1002\/cpt.3172","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T05:58:56Z","timestamp":1704347936000},"page":"498-505","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Subcutaneous Marzeptacog Alfa (Activated) for On\u2010Demand Treatment of Bleeding Events in Subjects With Hemophilia A or B With Inhibitors"],"prefix":"10.1002","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0165-363X","authenticated-orcid":false,"given":"Alan","family":"Faraj","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2839-4940","authenticated-orcid":false,"given":"Joakim","family":"Nyberg","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant E.","family":"Blouse","sequence":"additional","affiliation":[{"name":"Catalyst Biosciences  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Catalyst Biosciences  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-9686","authenticated-orcid":false,"given":"Ulrika S. H.","family":"Simonsson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"Crimson 1: A Phase 3 study to evaluate the efficacy and safety of subcutaneous marzeptocog alfa (activated) for on\u2010demand treatment of bleed events in subjects with hemophilia A or B with inhibitors.ISTH Congress Abstracts. <https:\/\/abstracts.isth.org\/abstract\/crimson\u20101\u2010a\u2010phase\u20103\u2010study\u2010to\u2010evaluate\u2010the\u2010efficacy\u2010and\u2010safety\u2010of\u2010subcutaneous\u2010marzeptocog\u2010alfa\u2010activated\u2010for\u2010on\u2010demand\u2010treatment\u2010of\u2010bleed\u2010events\u2010in\u2010subjects\u2010with\u2010hemophilia\u2010a\u2010or\u2010b\u2010with\u2010inhibitors\/>Accessed October 04 2023."},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12576"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14315"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24543"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516437"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2001.00534.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40271-014-0075-y"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04293.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12872"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.217133"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOPA.0000008157.26321.3c"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12487"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-017-0109-1"},{"key":"e_1_2_9_14_1","first-page":"153","article-title":"An example of statistical analysis of the text of Eugene Onegin Illustrating the association of trials into a chain","volume":"7","author":"Markov A.A.","year":"1913","journal-title":"Bull. 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World Federation of Hemophilia (2018). <https:\/\/elearning.wfh.org\/resource\/inhibitors\u2010in\u2010hemophilia\u2010a\u2010primer\/> Accessed January 14 2024."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2014201"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01808.x"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.3172","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T15:43:01Z","timestamp":1708098181000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.3172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,16]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/cpt.3172"],"URL":"https:\/\/doi.org\/10.1002\/cpt.3172","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"type":"print","value":"0009-9236"},{"type":"electronic","value":"1532-6535"}],"subject":[],"published":{"date-parts":[[2024,1,16]]},"assertion":[{"value":"2023-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}