Pharmacokinetics and safety of a novel recombinant human von Willebrand factor manufactured with a plasma-free method: a prospective clinical trial.

Safety and pharmacokinetics (PK) of recombinant von Willebrand factor (rVWF) combined at a fixed ratio with recombinant factor VIII (rFVIII) were investigated in 32 subjects with type 3 or severe type 1 von Willebrand disease (VWD) in a prospective phase 1, multicenter, randomized clinical trial. rVWF was well tolerated and no thrombotic events, inhibitors, or serious adverse events were observed. The PK of rVWF ristocetin cofactor activity, VWF antigen, and collagen-binding activity were similar to those of the comparator plasma-derived (pd) VWF-pdFVIII.

First and next generation native rFVIII in the treatment of hemophilia A. What has been achieved? Can patients be switched safely?

The introduction of plasma-derived human factor VIII (FVIII) and later human recombinant FVIII (rFVIII) has potentially allowed patients suffering from hemophilia A to have a quality of life and life expectancy similar to the population at large. One of the major achievements in molecular biology over the past 15 years was the sequencing of the gene coding for FVIII, leading eventually to the ability to isolate the human gene for FVIII and transfect cells to produce human rFVIII. The first rFVIII products, which are native full-length FVIII molecules, have proved to have an excellent efficacy and safety profile in patients with hemophilia A.