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Semin Thromb Hemost. 2012 Apr;38(3):274-81. doi: 10.1055/s-0032-1302442. Epub 2012 Feb 18.

Vatreptacog alfa from conception to clinical proof of concept.

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  • 1Haemostasis Biology, Novo Nordisk A/S, Måløv, Denmark. egpe@novonordisk.com

Abstract

Vatreptacog alfa is a genetically engineered variant of recombinant factor VIIa (rFVIIa) containing three amino acid changes. Aspartic acid, valine, and glutamine residues replace valine, glutamic acid, and methionine at positions 158, 296, and 298, respectively. These substitutions result in considerable enhancement of the intrinsic (tissue factor-independent) capability to activate factor X and the downstream hemostatic events are consequently augmented. The beneficial effects of vatreptacog alfa have been demonstrated in numerous in vitro systems attempting to mimic hemophilia and corroborated in in vivo models. Vatreptacog alfa has successfully passed through phase 1 and 2 clinical trials and the molecule is currently being explored in phase 3 clinical trial for the treatment of bleedings in hemophilia patients with inhibitors. This article describes the proposed mechanism behind the increased activity and action of vatreptacog alfa and reviews available data, which suggest that vatreptacog alfa could be a valuable addition to the existing portfolio of treatment options for hemophilia patients with inhibitors.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

PMID:
22510860
[PubMed - indexed for MEDLINE]
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