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 is cleaved to leave the activated factor IX (Factor IXa).1 Nonacog beta pegol was developed by Novo Nordisk and received its first global approval by the FDA on May 31, 2017,7 followed by the European Commission approval on June 2, 2017.13 Nonacog beta pegol was approved by Health Canada on November 29, 2017.14
- Type
- Biotech
- Groups
- Approved, Investigational
- Synonyms
- Coagulation Factor IX (Recombinant), GlycoPEGylated
- Nonacog beta pegol
Pharmacology
- Indication
Nonacog beta pegol is indicated in adults and children with hemophilia B (congenital factor IX deficiency or Christmas disease) for control and prevention of bleeding episodes as well as control and prevention of bleeding in the perioperative setting.11,12,13,14 It is also used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes.12,14
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Bleeding caused by hemophilia b •••••••••••• ••••••••••• •••••• •••••••• Management of Bleeding caused by hemophilia b •••••••••••• ••••••••••• •••••• ••••••••• Prophylaxis of Bleeding caused by hemophilia b •••••••••••• ••••••••••• •••••• ••••••••• Management of Bleeding caused by hemophilia b •••••••••••• ••••••••••• ••••• Prophylaxis of Bleeding caused by hemophilia b •••••••••••• ••••••••••• ••••• - Associated Therapies
- 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.8 In preclinical studies, whole blood clotting time activity was restored and the activated-partial thromboplastin time returned to normal limits. In clinical trials, the administration of nonacog beta pegol significantly increased the levels of factor IX in plasma and temporarily corrected the level of activated partial thromboplastin time.9 The effect of nonacog beta pegol translated into good hemostasis when used to treat bleeding on demand. A reduction of annualized bleeding rates was also observed when used as prophylaxis without the 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.10
- Mechanism of action
Nonacog beta pegol is activated by factor IXa and the tissue complex factor VII, whereby the peptide, including the 40kDa PEG moiety, is cleaved off. The resulting product from this activation process is recombinant factor IX with the same biological activity as endogenous coagulation factor IXa.8 The activated coagulation factor IX, in combination with factor VIIIa, activates the coagulation factor X to trigger the coagulation cascade and promote the conversion of prothrombin into thrombin. Thrombin drives the conversion of fibrinogen into fibrin for clot formation.3
Target Actions Organism ACoagulation factor VII cofactorHumans ACoagulation factor VIII cofactorHumans ACoagulation factor X agonistHumans - Absorption
The mean area under the curve (AUC)inf ranged from 46 to 91 IU*hours/mL in children and adults.14 In preclinical studies, there was a reduced accumulation of systemic drug after multiple dosing.10
- Volume of distribution
The volume of distribution varies depending on the patient's age. After single administration, the volume of distribution goes from 72 ml/kg for children less than 6 years of age, 68 ml/kg for adolescents between 7 and 12 years of age, 59 ml/kg in adolescents between 13 and 17 years of age, and 47 ml/kg for adults.[L1099] At steady state, the volume of distribution of nonacog beta pegol is 64 ml/kg.[L1099]
Nonacog beta pegol is not expected to accumulate in tissues.5
- Protein binding
Nonacog beta pegol is not expected to bind to plasma proteins.10
- Metabolism
After being taken up by cells, the proteinic component of nonacog beta pegol is degraded by lysosomes or endosomes.4 The PEG component of the drug is retained in the body 7.5 to 9 times longer than the original compound, as it is returned to circulation.8
- Route of elimination
The 40 kDa PEG component of nonacog beta pegol is eliminated in urine and feces taking approximately 49 and 40% of the administered dose respectively.5 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.10
- Half-life
The mean half-life ranged from 70 to 89 hours in children and adults.14
- Clearance
Mean clearance in children and adults ranged from 0.4 to 0.8 mL/hour/kg.14
- Adverse Effects
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There is limited information regarding acute toxicity and overdosage of nonacog beta pegol.
- 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. - 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 Rebinyn Powder, for solution 1000 unit / vial Intravenous Novo Nordisk 2018-03-23 Not applicable Canada 
Rebinyn Powder, for solution 3000 unit / vial Intravenous Novo Nordisk Not applicable Not applicable Canada Rebinyn Powder, for solution 500 unit / vial Intravenous Novo Nordisk 2018-03-23 Not applicable Canada Rebinyn Powder, for solution 2000 unit / vial Intravenous Novo Nordisk 2018-03-23 Not applicable Canada Refixia Injection, powder, for solution 3000 IU Intravenous Novo Nordisk 2023-02-08 Not applicable EU 
Categories
- Drug Categories
- 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]
- 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 News Release: Novo Nordisk receives US FDA approval of REBINYN® (nonacog beta pegol; N9-GP) [Link]
- FDA Blood Products Advisory Committee: Coagulation Factor IX (Recombinant), GlycoPEGylated N9-GP (nonacog beta pegol)_Meeting Briefing Document (April 4, 2017) [Link]
- FDA Blood Products Advisory Committee: BLA 125611_FDA Briefing Document (April 4, 2017) [Link]
- EMA Assessment Report: Refixia, INN-nonacog beta pegol [Link]
- DailyMed Label: REBINYN [Coagulation Factor IX (Recombinant), GlycoPEGylated] lyophilized powder for solution for intravenous injection [Link]
- Health Canada Product Monograph: REBINYN (nonacog beta pegol) Intravenous injection [Link]
- Summary of Product Characteristics: Refixia (nonacog beta pegol) intravenous injection [Link]
- Health Canada Approved Drug Products: REBINYN (nonacog beta pegol) Lyophilized powder for solution, intravenous (October 2022) [Link]
- External Links
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Hemophilia B 1 3 Completed Treatment Congenital Hematological Disorder / Hemophilia B 5 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 3000 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 3000 IU Injection, powder, for solution Intravenous 500 IU Solution Intravenous 1000 UI Injection, solution 1000 iu Injection, powder, lyophilized, for solution Intravenous 1000 IU Injection, solution 2000 iu Injection, solution 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
- Health Canada Approved Drug Products: REBINYN (nonacog beta pegol) Lyophilized powder for solution, intravenous (October 2022) [Link]
- 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
- FDA Blood Products Advisory Committee: Coagulation Factor IX (Recombinant), GlycoPEGylated N9-GP (nonacog beta pegol)_Meeting Briefing Document (April 4, 2017) [Link]
- Health Canada Approved Drug Products: REBINYN (nonacog beta pegol) Lyophilized powder for solution, intravenous (October 2022) [Link]
- 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
- FDA Blood Products Advisory Committee: Coagulation Factor IX (Recombinant), GlycoPEGylated N9-GP (nonacog beta pegol)_Meeting Briefing Document (April 4, 2017) [Link]
- Health Canada Approved Drug Products: REBINYN (nonacog beta pegol) Lyophilized powder for solution, intravenous (October 2022) [Link]
Drug created at December 22, 2017 14:27 / Updated at December 01, 2022 11:28