Identification
- Summary
Nonacog beta pegol is a recombinant coagulation Factor IX derivative used to treat hemophilia B.
- Generic Name
- Nonacog beta pegol
- DrugBank Accession Number
- DB13933
- Background
Nonacog beta pegol is a recombinant coagulation factor IX derivative. It is produced without animal-derived materials and with an attached 40kDa polyethylene glycol (PEG) molecule for peptide activation by a site-directed glycoPEGylation. Once activated, the activation molecule with PEG are cleaved to leave the activated factor IX (Factor IXa).1 Nonacog beta pegol was developed by Novo Nordisk, obtained EMA marketing authorisation in June 6, 2017.9
- Type
- Biotech
- Groups
- Approved, Investigational
- Synonyms
- Coagulation Factor IX (Recombinant), GlycoPEGylated
- Nonacog beta pegol
Pharmacology
- Indication
Nonacog beta pegol is indicated for the use in adults and children with hemophilia B for control and prevention of bleeding episodes, routine prophylaxis and perioperative management.10 In the EMA approval, it is also indicated for on-demand treatment of bleeding episodes.9 Hemophilia B is characterized by a deficiency in the coagulation factor IX which results in prolonged oozing after injuries and delayed or recurring bleeding prior wound healing. Hemophilia B patients present more frequent bleeding episodes during childhood and adolescence than in adulthood.7
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- Contraindications & Blackbox Warnings
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After nonacog beta pegol is activated by the coagulation factor IXa and tissue-coagulation factor VIIa, the peptide is cleaved off.10 In preclinical studies, once the peptide is free, there was a restoration of whole blood clotting time activity and the activated-partial thromboplastin time was returned to normal limits. In clinical trials, the administration of nonacog beta pegol significantly increased the levels of factor IX in plasma and temporarily correct the level of activated partial thromboplastin time.11 The effect of nonacog beta pegol translated into good hemostasis when used to treat bleeds on-demand and in a reduction of annualized bleeding rates when used as prophylaxis without formation of factor IX inhibitors, allergic reactions or thromboembolic complications.2 The reports in clinical trials have also shown a significant prolongation in the duration of the hemostatic effect.12
- Mechanism of action
Nonacog beta pegol is activated by the factor IXa and the tissue complex factor VII. When activated, the peptide including the 40kDa PEG moiety is cleaved off leaving an activated recombinant factor IX ready to be part of the coagulation cascade replacing the missing clotting factor IX.9 Thus, after activation, nonacog beta pegol will present the same mechanism of action than the endogenous coagulation factor IXa.10 The activated coagulation factor IX function is, in combination with the factor VIIIa, to activate the coagulation factor X to trigger the coagulation cascade that finalizes in the conversion of prothrombin into thrombin and the thrombin-driven conversion of fibrinogen into fibrin for the formation of a clot.3
Target Actions Organism ACoagulation factor VII cofactorHumans ACoagulation factor VIII cofactorHumans ACoagulation factor X agonistHumans - Absorption
In preclinical overdose studies, there was reported an AUC of 1200 IU/kg in rats and 3750 IU/kg in monkeys.11 In clinical studies, the absorption properties of nonacog beta pegol were AUC of 92 IU h/ml at steady state.9 In precliniacl studies, there was a reduced accumulation of systemic drug after multiple dosing.12
- Volume of distribution
The reported volume of distribution for nonacog beta pegol is variable depending on the patient's age. After single administration, the volume of distribution goes from 72 ml/kg when the patient is less than 6 years old, 68 ml/kg between 7-12 years old, 59 ml/kg between 13-17 years old and 47 ml/kg when the patient is over 18 years old.9 At steady state, the volume of distribution of nonacog beta pegol is 64 ml/kg.9
- Protein binding
Nonavog brta pegol is not expected to bind to plasma proteins.12
- Metabolism
Nonacog beta pegol is rapidly distributed with the highest distribution in the well-perfused tissues. The proteinic part of nonacog beta pegol is degraded over time leaving just the 40 kDa PEG in circulation for 7.5-9 times longer than the original compound.10 As previously reported, the nonacog beta pegol will undergo uptake into cells and the protein part will be degraded in the lysosomes/endosomes leaving the PEG part to return to the plasma.5
- Route of elimination
Nonacog beta pegol is eliminated from all tissues indicating that it will reach steady state in plasma and tissue but it will not accumulate. The 40 kDa PEG is eliminated by urine and feces taking approximately 49 and 40% of the administered dose respectively.6 The PEG part of the drug seems to be eliminated with a bi-phasic profile that was registered at 2-3 days and at 15-18 days.12
- Half-life
The terminal half life of nonacog beta pegol is in the range of 96-110 hours which is 5 times longer than an unmodified coagulation factor IX.4
- Clearance
The registered clearance rate of nonacog beta pegol at steady state is of 0.4 ml h/kg.9
- Adverse Effects
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There are reports indicating that long-term administration of nonacog beta pegol results in the development of cross-reacting neutralizing antibodies.11 Studies regarding carcinogenicity, genotoxicity and reproductive toxicity have not been made.9
- 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 Nonacog beta pegol can be decreased when used in combination with Abciximab. Acenocoumarol The therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Acenocoumarol. Alpha-1-proteinase inhibitor Alpha-1-proteinase inhibitor may increase the thrombogenic activities of Nonacog beta pegol. Alteplase The therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Alteplase. Aminocaproic acid The risk or severity of adverse effects can be increased when Aminocaproic acid is combined with Nonacog beta pegol. Ancrod The therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Ancrod. Anistreplase The therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Anistreplase. Antihemophilic factor (recombinant), PEGylated The therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Antihemophilic factor (recombinant), PEGylated. Antithrombin Alfa The therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Antithrombin Alfa. Antithrombin III human The therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Antithrombin III human. 
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- 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 Rebinyn Powder, for solution 2000 unit / vial Intravenous Novo Nordisk 2018-03-23 Not applicable Canada 
Rebinyn Powder, for solution 1000 unit / vial Intravenous Novo Nordisk 2018-03-23 Not applicable Canada Rebinyn Powder, for solution 500 unit / vial Intravenous Novo Nordisk 2018-03-23 Not applicable Canada Refixia Injection, powder, for solution 2000 IU Intravenous Novo Nordisk 2020-12-22 Not applicable EU 
Refixia Injection, powder, for solution 500 IU Intravenous Novo Nordisk 2020-12-22 Not applicable EU Refixia Injection, powder, for solution 1000 IU Intravenous Novo Nordisk 2020-12-22 Not applicable EU
Categories
- Drug Categories
- Alcohols
- Amino Acids, Peptides, and Proteins
- Biological Factors
- Blood Coagulation Factors
- Blood Proteins
- Compounds used in a research, industrial, or household setting
- Enzyme Precursors
- Enzymes and Coenzymes
- Ethylene Glycols
- Glycols
- Hemostatics
- Macromolecular Substances
- Pegylated agents
- Polymers
- Proteins
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 27Y83O992Q
- CAS number
- 1175512-71-6
References
- General References
- Collins PW, Moss J, Knobe K, Groth A, Colberg T, Watson E: Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX. J Thromb Haemost. 2012 Nov;10(11):2305-12. doi: 10.1111/jth.12000. [Article]
- Syed YY: Nonacog Beta Pegol: A Review in Haemophilia B. Drugs. 2017 Dec;77(18):2003-2012. doi: 10.1007/s40265-017-0836-8. [Article]
- Palta S, Saroa R, Palta A: Overview of the coagulation system. Indian J Anaesth. 2014 Sep;58(5):515-23. doi: 10.4103/0019-5049.144643. [Article]
- Mancuso ME: GlycoPEGylated factor IX: a new step forward. Blood. 2014 Dec 18;124(26):3836-7. doi: 10.1182/blood-2014-10-604983. [Article]
- Baumann A, Tuerck D, Prabhu S, Dickmann L, Sims J: Pharmacokinetics, metabolism and distribution of PEGs and PEGylated proteins: quo vadis? Drug Discov Today. 2014 Oct;19(10):1623-31. doi: 10.1016/j.drudis.2014.06.002. Epub 2014 Jun 11. [Article]
- Sternebring O, Christensen JK, Bjornsdottir I: Pharmacokinetics, tissue distribution, excretion, and metabolite profiling of PEGylated rFIX (nonacog beta pegol, N9-GP) in rats. Eur J Pharm Sci. 2016 Sep 20;92:163-72. doi: 10.1016/j.ejps.2016.06.025. Epub 2016 Jul 1. [Article]
- Konkle B., Huston H. and Fletcher S. (2017). Gene Reviews. University of Washington..
- Globe Newswire [Link]
- Novo Nordisk News [Link]
- FDA Advisory committees [Link]
- FDA Advisory committees [Link]
- EMA Reports [Link]
- External Links
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Congenital Hematological Disorder / Hemophilia B 2 3 Completed Treatment Congenital Hematological Disorder / Hemophilia B 3 1 Completed Treatment Congenital Hematological Disorder / Hemophilia B 1 Not Available Completed Not Available Hemophilia 1 Not Available Enrolling by Invitation Not Available Hemophilia B 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Powder, for solution Intravenous 1000 unit / vial Powder, for solution Intravenous 2000 unit / vial Powder, for solution Intravenous 500 unit / vial Injection, powder, for solution Intravenous 1000 IU Injection, powder, for solution Intravenous 2000 IU Injection, powder, for solution Intravenous 500 IU - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Soluble Bolourchian N., et al. 12(Suppl): 11-20. (2013)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Cofactor
- General Function
- Serine-type peptidase activity
- Specific Function
- Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, o...
- Gene Name
- F7
- Uniprot ID
- P08709
- Uniprot Name
- Coagulation factor VII
- Molecular Weight
- 51593.465 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Cofactor
- General Function
- Oxidoreductase activity
- Specific Function
- Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
- Gene Name
- F8
- Uniprot ID
- P00451
- Uniprot Name
- Coagulation factor VIII
- Molecular Weight
- 267007.42 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
- Gene Name
- F10
- Uniprot ID
- P00742
- Uniprot Name
- Coagulation factor X
- Molecular Weight
- 54731.255 Da
References
Drug created at December 22, 2017 14:27 / Updated at December 08, 2021 01:57