Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model
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Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model. / Pastoft, Anne Engedahl; Ezban, M.; Tranholm, M.; Lykkesfeldt, Jens; Lauritzen, B.
I: Haemophilia Online, Bind 19, Nr. 6, 2013, s. 913-919.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Prolonged effect of a new O-glycoPEGylated FVIII (N8-GP) in a murine saphenous vein bleeding model
AU - Pastoft, Anne Engedahl
AU - Ezban, M.
AU - Tranholm, M.
AU - Lykkesfeldt, Jens
AU - Lauritzen, B.
N1 - © 2013 John Wiley & Sons Ltd.
PY - 2013
Y1 - 2013
N2 - Prophylaxis in severe haemophilia significantly increases health-related quality of life for patients, but the dosing frequency still constitutes a challenge. Thus, there is a need for new treatment options, utilizing compounds with longer duration of action, while still maintaining potency. The objective of this study was to evaluate the acute and prolonged effects of a new glycoPEGylated recombinant factor VIII (rFVIII) (N8-GP) in a venous bleeding model in haemophilia A mice and to compare the efficacy and potency to turoctocog alfa (rFVIII). Following intravenous administration of turoctocog alfa or N8-GP to normal and FVIII-deficient mice, bleeding time and blood loss from a saphenous vein incision were evaluated in an acute dose-response study and a duration of action study. In the acute setting, N8-GP dose dependently reduced the number and duration of bleeding episodes as well as blood loss compared to FVIII-deficient mice, reaching statistical significance at doses as low as 5-10 U kg(-1) . In the duration of action study, a significantly prolonged and maintained effect of N8-GP was found for up to 48 h after dosing, whereas the effect of rFVIII was no longer present for any end-points 24 h after dosing. Seventy-two hours after dosing, no significant effect of either compound was found. This study shows a prolonged haemostatic effect of N8-GP compared to rFVIII supporting other recent studies that N8-GP may hold a potential to increase the quality of life for patients with haemophilia A by reducing dosing frequency.
AB - Prophylaxis in severe haemophilia significantly increases health-related quality of life for patients, but the dosing frequency still constitutes a challenge. Thus, there is a need for new treatment options, utilizing compounds with longer duration of action, while still maintaining potency. The objective of this study was to evaluate the acute and prolonged effects of a new glycoPEGylated recombinant factor VIII (rFVIII) (N8-GP) in a venous bleeding model in haemophilia A mice and to compare the efficacy and potency to turoctocog alfa (rFVIII). Following intravenous administration of turoctocog alfa or N8-GP to normal and FVIII-deficient mice, bleeding time and blood loss from a saphenous vein incision were evaluated in an acute dose-response study and a duration of action study. In the acute setting, N8-GP dose dependently reduced the number and duration of bleeding episodes as well as blood loss compared to FVIII-deficient mice, reaching statistical significance at doses as low as 5-10 U kg(-1) . In the duration of action study, a significantly prolonged and maintained effect of N8-GP was found for up to 48 h after dosing, whereas the effect of rFVIII was no longer present for any end-points 24 h after dosing. Seventy-two hours after dosing, no significant effect of either compound was found. This study shows a prolonged haemostatic effect of N8-GP compared to rFVIII supporting other recent studies that N8-GP may hold a potential to increase the quality of life for patients with haemophilia A by reducing dosing frequency.
KW - Faculty of Health and Medical Sciences
KW - haemophilia A
KW - mice
KW - PEGylation
KW - rFVIII
KW - venous bleeding
U2 - 10.1111/hae.12198
DO - 10.1111/hae.12198
M3 - Journal article
C2 - 23730746
VL - 19
SP - 913
EP - 919
JO - Haemophilia
JF - Haemophilia
SN - 1351-8216
IS - 6
ER -
ID: 104569930