Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein
Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein Uses, Dosage, Side Effects, Food Interaction and all others data.
Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein is a long-acting recombinant fusion protein used in the treatment of hemophilia B. It is comprised of a single molecule of human factor IX (FIX) covalently linked to the constant region (Fc) domain of human IgG1 via recombinant DNA technology in a human embryonic kidney cell line (HEK293H) . The presence of the Fc domain extends the terminal half-life which confers clinical benefits of prolonged therapeutic efficacy, less frequent intravenous injections for patient convenience and improved adherence to prophylaxis.
Hemophilia B is a blood disorder with an incidence of approximately once every 30,000 male births in all populations and ethnic groups . It is an X-linked genetic disease caused by mutation of the gene for coagulation protein factor IX (FIX), leading to decreased levels of endogenous factor IX and increased susceptibility to recurrent bleeding episodes caused spontaneously or as a result of accidental or surgical trauma . When untreated, most patients die from bleeding complications before 25 years of age . Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein acts as a replacement therapy to restore the levels of factor IX and allow normal hemostasis.
Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein was developed and marketed as Alprolix for intravenous injection by Biogen. It was first approved by the FDA in March 2014 and later approved by the EMA in May 2016. Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein treatment demonstrated good tolerability with no reports of inhibitor development in clinical studies .
Table Of contents
| Trade Name | Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein |
| Generic | Eftrenonacog alfa |
| Eftrenonacog alfa Other Names | Coagulation factor IX recombinant immunoglubulin g1 fusion protein, Eftrenonacog alfa, Recombinant human coagulation factor IX, FC Fusion protein |
| Type | |
| Weight | 98000.0 Da (Approximate) |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein is a recombinant Factor IX used to treat and prevent bleeding in hemophilia B.
Indicated for the treatment and prophylaxis of bleeding in patients of all age with haemophilia B (congenital factor IX deficiency).
Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein is also used to associated treatment for these conditions: Bleeding, Perioperative Blood Loss
How Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein works
The coagulation protein factor IX (FIX) is a vitamin K-dependent coagulation factor and one of the critical serine proteases involved in the coagulation cascade. Upon activation by factor XIa in the intrinsic coagulation pathway and by the factor VII/tissue factor complex in the extrinsic pathway, factor IX, in combination with factor VIII, activates factor X. Activated factor X mediates the conversion of prothrombin to thrombin which sequentially leads to thrombin converting fibrinogen into fibrin. A blood clot is then formed . With a mutation in the gene encoding the coagulation protein factor IX (FIX), patients with hemophilia B have factor IX deficiency and are at high risk for recurrent bleeding episodes.
Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein is composed of a single molecule of recombinant FIX (rFIX) covalently fused to the dimeric Fc domain of immunoglobulin (Ig) G1 (rFIXFc). It serves as a replacement therapy to increase the plasma levels of factor IX thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies . The Fc region of human immunoglobulin G1 binds with the neonatal Fc receptor which is expressed throughout life as part of a naturally occurring pathway that protects immunoglobulins from lysosomal degradation by cycling these proteins back into circulation, resulting in their long plasma half-life. The binding of eftrenonacog alfa to the neonatal Fc receptor delays degradation and recycles the fusion protein back into circulation for increased plasma half life and prolonged therapeutic action .
Toxicity
Based on findings from a rabbit thrombogenicity test and rat or monkey repeated-dose toxicity studies, eftrenonacog alfa displays no special hazards for humans. Studies to investigate the genotoxicity, carcinogenicity, toxicity to reproduction or embryo-foetal development have not been conducted. Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein has shown to cross the placenta in small amounts according to a mouse placental transfer study .
Food Interaction
No interactions found.Volume of Distribution
Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean volume of distribution at steady-state (Vss) was 303.4 mL/kg . In pediatric and adolescent patients (< 18 years of age) receiving the same dose, the mean Vss ranged from 289 to 365.1 mL/kg .
Elimination Route
Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean peak plasma concentration (Cmax) was 46.10 IU/dL . The mean area under the FIX activity time curve (AUC) was 31.58 Uxh/dL per IU/kg . In pediatric and adolescent patients (< 18 years of age) receiving the same dose, the mean AUC ranged from 22.71 to 29.50 Uxh/dL per IU/kg .
Half Life
Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean terminal half life (t1/2) was 77.6 hours . In pediatric and adolescent patients (< 18 years of age) receiving the same dose, the mean t1/2 ranged from 66.49 to 82.22 hours .
Clearance
Following administration of a single intravenous dose of 50 IU/kg of eftrenonacog alfa in patients ≥19 years of age with hemophilia B, the mean clearance (CL) was 3.17 mL/h/kg . In pediatric and adolescent patients (< 18 years of age) receiving the same dose, mean CL ranged from 3.390 to 4.365 mL/h/kg .
Elimination Route
Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein is expected to undergo renal clearance .
Innovators Monograph
You find simplified version here Coagulation Factor IX Recombinant Immunoglubulin G1 Fusion Protein
