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Identification
- Summary
Eftrenonacog alfa is a recombinant Factor IX used to treat and prevent bleeding in hemophilia B.
- Brand Names
- Alprolix
- Generic Name
- Eftrenonacog alfa
- DrugBank Accession Number
- DB11608
- Background
Eftrenonacog alfa 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) 1. 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 2. 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 Label. When untreated, most patients die from bleeding complications before 25 years of age 2. Eftrenonacog alfa acts as a replacement therapy to restore the levels of factor IX and allow normal hemostasis.
Eftrenonacog alfa 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. Eftrenonacog alfa treatment demonstrated good tolerability with no reports of inhibitor development in clinical studies 1.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Blood factors - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 98000.0 Da (Approximate)
- Sequences
- Not Available
- Synonyms
- Coagulation factor IX recombinant immunoglubulin g1 fusion protein
- Eftrenonacog alfa
- Recombinant human coagulation factor IX, FC Fusion protein
- External IDs
- BIIB-029
- RFIXFC
Pharmacology
- Indication
Indicated for the treatment and prophylaxis of bleeding in patients of all age with haemophilia B (congenital factor IX deficiency).
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prophylaxis of Bleeding caused by hemophilia b •••••••••••• ••••••••••• •••••• ••••••••• Management of Bleeding caused by hemophilia b •••••••••••• ••••••••••• •••••• ••••••••• Management of Bleeding caused by hemophilia b •••••••••••• ••••••••••• •••••• ••••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
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In two multinational, phase III studies in previously treated children, adolescents and adults with severe haemophilia B, eftrenonacog alfa prophylaxis resulted in low median annualized bleeding rates (ABRs), and was associated with reductions in median weekly factor consumption and dosing frequency compared with pre-study FIX regimens. The extension of those studies demonstrated effectiveness in the treatment of bleeding episodes and when used in the perioperative setting in all age groups 1. In animal models, a single intravenous dose of eftrenonacog alfa displayed half values approximately three- to four-fold longer than those seen with recombinant FIX 1.
- Mechanism of action
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 Label. 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.
Eftrenonacog alfa 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 Label. 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 Label,2.
- Absorption
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 Label. The mean area under the FIX activity time curve (AUC) was 31.58 Uxh/dL per IU/kg Label. 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 Label.
- 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 Label. In pediatric and adolescent patients (< 18 years of age) receiving the same dose, the mean Vss ranged from 289 to 365.1 mL/kg Label.
- Protein binding
Not Available
- Metabolism
The Fc domain of eftrenonacog alfa is expected to undergo lysosomal degradation while the remaining recombinant FIX (rFIX) portion is expected to be metabolized by the same pathway as endogenous factor IX.
- Route of elimination
Eftrenonacog alfa is expected to undergo renal clearance 2.
- 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 Label. 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 Label.
- 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 Label. 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 Label.
- Adverse Effects
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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. Eftrenonacog alfa has shown to cross the placenta in small amounts according to a mouse placental transfer study Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The therapeutic efficacy of Eftrenonacog alfa can be decreased when used in combination with Abciximab. Acenocoumarol The therapeutic efficacy of Eftrenonacog alfa can be decreased when used in combination with Acenocoumarol. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Eftrenonacog alfa. Aducanumab The risk or severity of adverse effects can be increased when Eftrenonacog alfa is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Eftrenonacog alfa. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alprolix Kit 3000 [iU]/5mL Intravenous Biogen Inc. 2014-05-05 2020-12-31 US 
Alprolix Injection, powder, for solution 1000 IU Intravenous SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2021-01-12 Not applicable EU 
Alprolix Kit 500 [iU]/5mL Intravenous Biogen Inc. 2014-05-05 2021-04-30 US Alprolix Kit; Powder, for solution 4000 unit / vial Intravenous Sanofi Aventis Deutschland Gmb H Not applicable Not applicable Canada 
Alprolix Kit; Powder, for solution 3000 unit / vial Intravenous Sanofi Aventis Deutschland Gmb H 2016-01-15 Not applicable Canada
Categories
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Biological Factors
- Blood Coagulation Factors
- Blood Proteins
- Enzyme Precursors
- Enzymes and Coenzymes
- Globulins
- Hemostatics
- Immunoglobulin Constant Regions
- Immunoglobulin Fragments
- Immunoglobulins
- Immunoproteins
- Peptide Fragments
- Peptides
- Protein Precursors
- Proteins
- Recombinant Proteins
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 02E00T2QDE
- CAS number
- 1270012-74-2
References
- General References
- Hoy SM: Eftrenonacog Alfa: A Review in Haemophilia B. Drugs. 2017 Jul;77(11):1235-1246. doi: 10.1007/s40265-017-0778-1. [Article]
- Miguelino MG, Powell JS: Clinical utility and patient perspectives on the use of extended half-life rFIXFc in the management of hemophilia B. Patient Prefer Adherence. 2014 Aug 8;8:1073-83. doi: 10.2147/PPA.S54951. eCollection 2014. [Article]
- FDA Approved Drug Products: ALPROLIX [coagulation factor IX (recombinant), Fc fusion protein], lyophilized powder for solution, for intravenous injection [Link]
- External Links
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Hemophilia B 1 somestatus stop reason just information to hide Not Available Completed Not Available Hemophilia 1 somestatus stop reason just information to hide Not Available Completed Not Available Hemophilia A / Hemophilia B 1 somestatus stop reason just information to hide Not Available Completed Not Available Hemophilia B 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Hemophilia A / Hemophilia B 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 1000 IU Injection, powder, for solution Intravenous 2000 IU Injection, powder, for solution Intravenous 250 IU Injection, powder, for solution Intravenous 3000 IU Injection, powder, for solution Intravenous 500 IU Kit Intravenous 1000 [iU]/5mL Kit Intravenous 2000 [iU]/5mL Kit Intravenous 250 [iU]/5mL Kit Intravenous 3000 [iU]/5mL Kit Intravenous 4000 [iU]/5mL Kit Intravenous 500 [iU]/5mL Kit; powder, for solution Intravenous 1000 [iU]/5mL Kit; powder, for solution Intravenous 1000 unit / vial Kit; powder, for solution Intravenous 2000 unit / vial Kit; powder, for solution Intravenous 2000 [iU]/5mL Kit; powder, for solution Intravenous 250 unit / vial Kit; powder, for solution Intravenous 250 [iU]/5mL Kit; powder, for solution Intravenous 3000 [iU]/5mL Kit; powder, for solution Intravenous 3000 unit / vial Kit; powder, for solution Intravenous 4000 [iU]/5mL Kit; powder, for solution Intravenous 4000 unit / vial Kit; powder, for solution Intravenous 500 unit / vial Kit; powder, for solution Intravenous 500 [iU]/5mL Injection, powder, lyophilized, for solution Intravenous 250 IU - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Drug created at June 24, 2016 19:21 / Updated at May 24, 2023 10:27