{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T15:48:49Z","timestamp":1762876129380,"version":"3.40.5"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009431","name":"Baxalta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009431","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>SHP656 is the first factor VIII (FVIII) product developed using polysialylation (PSA) technology, in which full\u2010length recombinant (r) FVIII (anti\u2010haemophilic factor [recombinant]) is conjugated with a 20\u00a0kDa PSA polymer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To compare the safety, immunogenicity and pharmacokinetics of SHP656 vs the parent rFVIII (octocog alfa) after single infusions of 25\u201075\u00a0IU\/kg in patients with severe haemophilia A (FVIII activity &lt;1%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Multinational, phase 1, prospective, open\u2010label, two\u2010period, fixed\u2010sequence, dose\u2010escalation trial (clinicaltrials.gov NCT02716194). Patients received single doses of rFVIII and then SHP656 sequentially at the same dose: 25\u00a0\u00b1\u00a03\u00a0IU\/kg (Cohort 1), 50\u00a0\u00b1\u00a05\u00a0IU\/kg (Cohort 2) and 75\u00a0\u00b1\u00a05\u00a0IU\/kg (Cohort 3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty patients received rFVIII: 11 in Cohort 1, 16 in Cohort 2 and 13 in Cohort 3. Two patients withdrew before receiving SHP656, leaving 38 patients who completed the study and received both treatments. No treatment\u2010related adverse events (AEs), serious AEs, deaths, study withdrawals, thrombotic events or allergic reactions were reported; and no significant treatment\u2010related changes in laboratory parameters or vital signs. No patients developed FVIII inhibitors or antibodies to PSA. FVIII activity was significantly prolonged following SHP656 administration vs rFVIII with an approximately 1.5\u2010fold extension in mean residence time (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). Exposure increased proportional to the SHP656 dose over the 25\u201075\u00a0IU\/kg dose range.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Polysialylation of rFVIII confers a half\u2010life extension similar to that of approved extended half\u2010life products that use either PEGylation or Fc fusion technology and was not associated with any treatment\u2010related adverse events.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13878","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T15:29:45Z","timestamp":1574954985000},"page":"47-55","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["SHP656, a polysialylated recombinant factor VIII (PSA\u2010rFVIII): First\u2010in\u2010human study evaluating safety, tolerability and pharmacokinetics in patients with severe haemophilia A"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3600-8536","authenticated-orcid":false,"given":"Andreas","family":"Tiede","sequence":"first","affiliation":[{"name":"Hannover Medical School Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4351-1014","authenticated-orcid":false,"given":"Geoffrey","family":"Allen","sequence":"additional","affiliation":[{"name":"Baxalta US Inc, a member of the Takeda group of companies Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Bauer","sequence":"additional","affiliation":[{"name":"Baxalta Innovations GmbH, a member of the Takeda group of companies Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6690-8586","authenticated-orcid":false,"given":"Pratima","family":"Chowdary","sequence":"additional","affiliation":[{"name":"Katharine Dormandy Haemophilia and Thrombosis Centre Royal Free Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Collins","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity School of Medicine Cardiff University Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brahm","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Baxalta US Inc, a member of the Takeda group of companies Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyu Jeanne","family":"Jiang","sequence":"additional","affiliation":[{"name":"Baxalta US Inc, a member of the Takeda group of companies Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"K\u04e7ck","sequence":"additional","affiliation":[{"name":"IQVIA Overland Park KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"Tak\u00e1cs","sequence":"additional","affiliation":[{"name":"Semmelweis University Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita","family":"Timofeeva","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution of Science \u201cKirov Scientific and Research Institute of Hematology and Blood Transfusion of Federal Medico\u2010Biological Agency\u201d Kirov Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Wolfsegger","sequence":"additional","affiliation":[{"name":"Baxalta Innovations GmbH, a member of the Takeda group of companies Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shouryadeep","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Baxalta US Inc, a member of the Takeda group of companies Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,11,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01208.x"},{"key":"e_1_2_10_3_1","unstructured":"World Federation of Hemophilia.Guidelines for the management of hemophilia.https:\/\/www1.wfh.org\/publication\/files\/pdf-1472.pdf. 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