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Blood, 15 January 2008, Vol. 111, No. 2, pp. 672-679. Prepublished online as a Blood First Edition Paper on October 31, 2007; DOI 10.1182/blood-2007-07-098913. This Article Full Text (PDF) All Versions of this Article: blood-2007-07-098913v1 111/2/672    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Prasad, S. Articles by Johnson, K. W Search for Related Content PubMed PubMed Citation Articles by Prasad, S. Articles by Johnson, K. W Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 3, 2007 Accepted September 29, 2007 Efficacy and safety of a new-class of hemostatic drug candidate, AV513, in hemophilia A dogs Srinivasa Prasad*, David Lillicrap, Andrea Labelle, Sabine Knappe, Tracy Keller, Erin Burnett, Sandra Powell, and Kirk W Johnson Pre-clinical department, Avigen Inc, Alameda, CA, United States Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada * Corresponding author; email: sprasad{at}avigen.com. AV513 is a select fucoidan, a sulfated polysaccharide of botanical origin, with procoagulant activity. It inhibits Tissue Factor Pathway Inhibitor (TFPI) activity and accelerates clotting of human hemophilia A and B plasma. In prior work, subcutaneous administration of AV513 to hemophilia A mice improved hemostasis. The current studies were designed to evaluate potential efficacy and safety in hemophilia A dogs with minimally increased hemostasis following Factor VIII gene transfer (AAV-FVIII) and in treatment-naive severe hemophilia A dogs. AV513 administered subcutaneously to low-FVIII dogs over multiple weeks resulted in improved hemostasis as exhibited in thromboelastography (TEG) and cuticle bleeding time (CBT) tests. Moreover, AV513 administered orally in AAV-FVIII dogs and treatment-naive severe hemophilia A dogs over a multi-week dose-escalating period yielded correction to normal ranges in both TEG and CBT end points at 5-15 mg/kg and 15-20 mg/kg dose levels, respectively. In all three separate studies, throughout their duration, AV513 was well-tolerated by the dogs without any adverse events. Additional pharmacological characterization of AV513 included intravenous pharmacokinetic analysis in rats. In summary, the combination of safety and efficacy in two global tests of hemostasis in the hemophilia A dog model indicate that further evaluation of AV513 as a hemostatic agent in hemophilia A is warranted. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Duckers, P. Simioni, L. Spiezia, C. Radu, S. Gavasso, J. Rosing, and E. Castoldi Low plasma levels of tissue factor pathway inhibitor in patients with congenital factor V deficiency Blood, November 1, 2008; 112(9): 3615 - 3623. [Abstract] [Full Text] [PDF]

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