[Recombinant activated factor VII: a new treatment for hemophilia]

Abstract

Recombinant factor VIIa (NovoSeven, NovoNordisk) initiates coagulation in inhibitor patients who either develop alloantibodies to clotting factors or those with acquired haemophilia. The human gene for FVII was transfected into a baby hamster kidney (BHK) cell line which secretes FVII in a single-chain form. Recombinant FVII is purified from the medium by four chromatographic steps including immunoaffinity chromatography with a monoclonal anti-FVII. During this process rFVII undergoes autoactivation to rFVIIa. NovoSeven does not contain any stabilising protein including human albumin. The SA is 50 KU/mg, the concentration is 0.6 mg/mL. Recovery is 45%, clearance is 31 mL/h/kg, the half-life was estimated between 2 and 3 hours. Combined to tissue factor rFVIIa directly activates factor X without implication of FVIIIa and FIXa. There is no systemic coagulation activation. Efficacy was assessed from data derived largely from the Compassionate Use Programme and clinical studies using rFVIIa as first line therapy. Various situations were proven to be efficiently resolved with rFVIIa including surgeries. Usual dosages are 90-120 mcg/kg administered every 2-3 hours. There were no side effects even in cases of prolonged administration. Drawbacks are the short half-life and the cost of the product.