Repeated short-interval administration of efanesoctocog alfa is not associated with increased global coagulation potential in hemophilia A mice
摘要
Efanesoctocog alfa is an extended half-life recombinant factor VIII (FVIII) designed for prophylaxis in hemophilia A (HA). However, global coagulation potential after repeated short-interval dosing remains unclear. We assessed coagulation potential following repeated short-interval administration of efanesoctocog alfa. Efanesoctocog alfa and rurioctocog alfa (1, 2, and 3 IU/mL) were added to FVIII-deficient plasma samples, and coagulation potential was assessed using thrombin generation assays. Efanesoctocog alfa and rurioctocog alfa were intravenously administered at 100 IU/kg to HA mice once every 24 h for three consecutive days. Coagulation function was assessed by rotational thromboelastometry. Activated partial thromboplastin time (aPTT), FVIII activity by chromogenic assay (FVIII:C), thrombin–antithrombin complex (TAT), and D-dimer were measured 5 min after each dose. Thrombin generation potential in FVIII-deficient plasma spiked with efanesoctocog alfa was comparable to that in plasma spiked with rurioctocog alfa. In HA mice, rotational thromboelastometry parameters, aPTT, TAT, and D-dimer were similar with efanesoctocog alfa and rurioctocog alfa, whereas FVIII:C by chromogenic assay was higher with efanesoctocog alfa than with rurioctocog alfa. In conclusion, global coagulation potential after short-interval administration of efanesoctocog alfa was similar to that after rurioctocog alfa under the experimental conditions.