ABSTRACT
Recombinant factor VIIa (rFVIIa) is used in the management of bleeding in patients with hemophilia. A generic biosimilar version of NovoSeven is also developed (AryoSeven). To compare the activation profile of NovoSeven and AryoSeven, 2 commercially available protein complex concentrates (PCCs) were used. Profilnine activated by RecombiPlasTin 2G resulted in conversions of prothrombin to prethrombin and thrombin at 5 to 30 minutes. However, addition of rFVIIa at final concentration range of 0.25 to 0.5 µg/mL to the same mixture resulted in total conversion of prothrombin to thrombin with a doublet at 36 kDa. Recombinant factor VIIa alone did not generate thrombin in native Beriplex, and the addition of rFVIIa to Beriplex failed to generate thrombin. Beriplex activated by RecombiPlasTin 2G resulted in complete conversion of prothrombin to thrombin. Both NovoSeven and AryoSeven exhibited similar activation profiles. These studies indicate that the activation of PCCs by both rFVIIa preparations results in comparable generation of thrombin.
Subject(s)
Blood Coagulation Factors/drug effects , Factor VIIa/pharmacology , Hemorrhage/drug therapy , Humans , Prothrombin/drug effects , Prothrombin/metabolism , Recombinant Proteins/pharmacology , Thrombin/metabolismABSTRACT
Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Copenhagen, Denmark) is used to control bleeding in patients with hemophilia. A generic version of FVIIa was developed by AryoGen (Tehran, Iran). This study compared the composition and functional activities of AryoSeven and NovoSeven. Each product was compared at equigravimetric (1 mg/mL) stock solution for protein content. The proteomic profile was obtained using surface-enhanced laser desorption ionization mass spectrometry. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis was carried out to determine the protein profile and Western blotting was performed using a polyclonal rabbit antihuman FVIIa antibody. The FVIIa-related antigen was also measured using a commercially available enzyme-linked immunosorbent assay method. Functional assay included the prothrombin time correction in FVII-deficient plasma. The protein content was comparable in 2 products and the mass spectra analysis showed a single peak at 50 kDa in all products. The SDS-PAGE and immunoblotting studies were comparable. Both products exhibited similar coagulant properties in different assays.
Subject(s)
Biosimilar Pharmaceuticals/analysis , Biosimilar Pharmaceuticals/chemistry , Factor VIIa/analysis , Factor VIIa/chemistry , Animals , Electrophoresis, Polyacrylamide Gel , Humans , Prothrombin Time , Rabbits , Recombinant Proteins/analysis , Recombinant Proteins/chemistryABSTRACT
Currently, several newer oral anticoagulants namely dabigatran (anti-IIa), rivaroxaban (anti-Xa), and apixaban are available for various clinical implications. Another oral anti-Xa edoxaban is under development. A parenteral anti-Xa drug namely otamixaban is also under development for cardiovascular interventions. Bleeding complications have been reported in the new oral anticoagulants and have been managed by conventional approaches with limited success. Prothrombin complex concentrates (PCCs) are reported to neutralize the anticoagulant activity of these agents. The PCCs are also able to generate endogenous factor Xa and IIa along with other proteases that are capable of neutralizing the circulating anti-Xa or anti-IIa activities of the newer anticoagulants. The generation of Xa and IIa is also dependent on the type of tissue factor available for their activation. These reported studies suggest that different tissue factors differentially activate a PCC namely Profilnine SD. Furthermore, dabigatran differs from rivaroxaban and other factor Xa inhibitors in its inhibitory profile.
