Faster onset of effect and greater efficacy of NN1731 compared with rFVIIa, aPCC and FVIII in tail bleeding in hemophilic mice.
BACKGROUND
Recombinant factor VIIa (rFVIIa, Novoseven) is currently used to control bleeding in hemophiliacs with inhibitors. A new rFVIIa variant, NN1731, with increased activity on the surface of activated platelets, has demonstrated a more potent and faster onset of reactivity than rFVIIa in various in vitro models. The present study aimed to investigate whether this translates into greater efficacy and faster promotion of hemostasis in vivo.


RESULTS
In a severe tail-bleeding model in hemophilia A mice, NN1731 demonstrated significantly greater efficacy than rFVIIa, plasma-derived activated prothrombin complex concentrate (pd-aPCC, FEIBA or FVIII (Refacto). Assessment of the blood loss over time showed that NN1731 significantly and dose-dependently reduced the blood loss in the first 5-min observation period, whereas the effect of rFVIIa, FVIII and pd-aPCC first became evident 5-10 min after injury.


CONCLUSIONS
This study shows that NN1731 has a greater efficacy and faster resolution of bleeding in a severe bleeding model in hemophilia A mice compared with any of the other agents tested.
Holmberg
H L
HL
Department of Haemostasis Pharmacology, Novo Nordisk, Maaloev, Denmark.
Lauritzen
B
B
Tranholm
M
M
Ezban
M
M
D000818:Animals; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005167:Factor VII / Q000627:therapeutic use*; D005169:Factor VIII / Q000627:therapeutic use; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D006470:Hemorrhage; D006487:Hemostasis; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors
D001779:Blood Coagulation Factors; C519901:NN1731; D011994:Recombinant Proteins; C427184:recombinant factor VIII SQ; D005167:Factor VII; D005169:Factor VIII; C103587:recombinant FVIIa; C065655:anti-inhibitor coagulant complex; D015942:Factor VIIa