Recombinant coagulation factor VIIa--from molecular to clinical aspects of a versatile haemostatic agent.
Recombinant factor VIIa (rFVIIa, NovoSeven) is currently the only bypassing agent produced by recombinant technology for the treatment of haemophiliacs whose disease is complicated by inhibitory antibodies. In addition, recombinant production of FVIIa has made it widely available for a variety of purposes and accelerated the growth of our knowledge about FVIIa by generating an abundance of clinical and biochemical data. This fascinating molecule has turned out to be a safe haemostatic agent with great potential in the clinic and has inspired the generation of improved variants currently in (pre-)clinical testing. The present review describes the structural and functional aspects of FVIIa, followed by sections dealing with the manufacturing, therapeutic mechanism of action, clinical development and experience with rFVIIa.
Persson
Egon
E
Biopharmaceuticals Research Unit, Novo Nordisk A/S, Måløv, Denmark. egpe@novonordisk.com
Bolt
Gert
G
Steenstrup
Thomas D
TD
Ezban
Mirella
M
D004345:Drug Industry / Q000379:methods; D015942:Factor VIIa / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D006490:Hemostatics / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D011994:Recombinant Proteins / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D006490:Hemostatics; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa