BeneFix

Pharmacotherapeutic group: Antihaemorrhagics, blood coagulation factor IX; ATC code: B02BD04 Mechanism of action BeneFIX contains recombinant coagulation factor IX, (nonacog alfa).‍‍‍‍‍‍​​​‍​​​​​​ Recombinant coagulation factor IX is a single chain glycoprotein with an approximate molecular mass of 55,000 Daltons that is a member of the serine protease family of vitamin K-dependent coagulation factors. Recombinant coagulation factor IX is a recombinant DNA-based protein therapeutic which has structural and functional characteristics comparable to endogenous factor IX. Factor IX is activated by factor VII/tissue factor complex in the extrinsic pathway as well as factor XIa in the intrinsic coagulation pathway. Activated factor IX, in combination with activated factor VIII, activates factor X. This results ultimately in the conversion of prothrombin to thrombin. Thrombin then converts fibrinogen into fibrin and a clot can be formed. Factor IX activity is absent or greatly reduced in patients with haemophilia B and substitution therapy may be required. Pharmacodynamic effects Haemophilia B is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor IX and results in profuse bleeding into joints, muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma. By replacement therapy the plasma levels of factor IX is increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies. Paediatric population Efficacy analysis in study 3090A1-301-WW was based on 22 evaluable paediatric subjects on prophylaxis regimen including 4 on-demand patients who shortly changed to prophylaxis. Two patients underwent surgical procedures (circumcision and port-a-catheter insertion). Safety analysis of 25 evaluable patients reflected a safety profile as expected. The only documented serious adverse event related with BeneFIX was reported from the only included PUP, who experienced hypersensitivity and inhibitor development. In two open-label studies BeneFIX was found to be safely administered at 100 IU/kg once- weekly. However, the half-life of the product (see section 5.2) and the limited pharmacokinetic study data for the once-weekly regimen do not allow recommending this regimen in general for long-term prophylaxis in severe haemophilia B patients.