title: Turoctocog alfa: an evidence-based review of its potential in the treatment of hemophilia A.
abstract: Turoctocog alfa is the first B-domain-truncated third generation recombinant coagulation factor VIII (FVIII) product. Nonclinical in vitro and animal model studies have demonstrated that turoctocog alfa has similar functional potency and hemostatic efficacy as comparator FVIII products. With respect to discrepancies in the level of FVIII concentrate in plasma of current FVIII products on comparing measurement results between one-stage clot and chromogenic assays, there was no difference in the in vitro turoctocog alfa study; however, measured FVIII concentrate in field study was higher with the chromogenic assay (1.08 IU/mL) than with one-stage assay (0.83 IU/mL). Two published clinical studies on previously treated patients (PTPs) and clinical pharmacokinetics have described that the pharmacokinetic parameters are similar, and the safety and efficacy for prevention and treatment for bleeding are also similar to those of standard half-life FVIII products. Three clinical trials are ongoing to assess the long-term safety and efficacy of turoctocog alfa for PTPs and previously untreated patients. Those data will be published in the near future, and it will be possible to use turoctocog alfa for all hemophilia patients. However, studies will be needed to confirm the turoctocog alfa profile, such as the stability of dissolved turoctocog alfa over 24 hours at room temperature and post-marketing clinical research aimed at meeting Europe Medicines Agency post-marketing safety and efficacy requirements in PTPs. It is recommended to wait before using turoctocog alfa for previously untreated patients and major surgery until further data have been collected and published.
authors.affiliation: Department of Joint Surgery, Research Hospital of the Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takedani
authors.affiliation: Department of Joint Surgery, Research Hospital of the Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hirose
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D005169:Factor VIII / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D015394:Molecular Structure
chemical_list: C577506:recombinant factor VIII N8; D005169:Factor VIII
keywords: B-domain-truncated; chromogenic assay; hemophilia A; previous untreated patients; third generation factor VIII product
references.citation: Haemophilia. 2012 Jan;18(1):139-45
references.pmid: 21771205
references.citation: Haemophilia. 2010 Sep 1;16(5):740-6
references.pmid: 20398072
references.citation: J Thromb Haemost. 2004 Apr;2(4):623-8
references.pmid: 15102018
references.citation: Thromb Haemost. 2000 Jun;83(6):811-6
references.pmid: 10896230
references.citation: Haemophilia. 2007 Jan;13(1):30-7
references.pmid: 17212722
references.citation: Thromb Res. 2007;119(1):1-13
references.pmid: 16487577
references.citation: Haemophilia. 2010 Mar;16(2):349-59
references.pmid: 19906157
references.citation: Haemophilia. 2011 Nov;17(6):854-9
references.pmid: 21443634
references.citation: J Biol Chem. 1986 Sep 25;261(27):12574-8
references.pmid: 3017981
references.citation: Haemophilia. 2013 Sep;19(5):691-7
references.pmid: 23647704
references.citation: Bull World Health Organ. 1995;73(5):691-701
references.pmid: 8846496
references.citation: Haemophilia. 2003 Jan;9(1):38-49
references.pmid: 12558777
references.citation: J Blood Med. 2010;1:183-95
references.pmid: 22282697
references.citation: J Thromb Haemost. 2012 Mar;10(3):359-67
references.pmid: 22212248
references.citation: Biologics. 2009;3:117-25
references.pmid: 19707401
references.citation: Haemophilia. 2011 Jul;17(4):695-702
references.pmid: 21426445
references.citation: Haemophilia. 2010 Nov;16(6):878-87
references.pmid: 20546031
references.citation: Haemophilia. 2012 Sep;18(5):782-8
references.pmid: 22500820
references.citation: Haemophilia. 2015 Jan;21(1):e19-25
references.pmid: 25458982
references.citation: Haemophilia. 2013 Sep;19(5):698-705
references.pmid: 23651313
references.citation: Blood. 1993 Jun 1;81(11):2925-35
references.pmid: 8499631
references.citation: Haemophilia. 2013 Jan;19(1):e1-47
references.pmid: 22776238
references.citation: Haemophilia. 2015 Jan;21(1):34-40
references.pmid: 25273984
references.citation: Haemophilia. 2011 Sep;17(5):e963-8
references.pmid: 21682818
references.citation: Haemophilia. 2014 Jul;20(4):527-34
references.pmid: 24471912
references.citation: N Engl J Med. 2001 Jun 7;344(23):1773-9
references.pmid: 11396445