Nonacog beta pegol

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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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofBleeding caused by hemophilia b••••••••••••••••••••••• •••••• ••••••••
Management ofBleeding caused by hemophilia b••••••••••••••••••••••• •••••• •••••••••
Prophylaxis ofBleeding caused by hemophilia b••••••••••••••••••••••• •••••• •••••••••
Management ofBleeding caused by hemophilia b••••••••••••••••••••••• •••••
Prophylaxis ofBleeding caused by hemophilia b••••••••••••••••••••••• •••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

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

TargetActionsOrganism
ACoagulation factor VII
cofactor
Humans
ACoagulation factor VIII
cofactor
Humans
ACoagulation factor X
agonist
Humans
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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Toxicity

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.
DrugInteraction
AbciximabThe therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Abciximab.
AcenocoumarolThe therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Acenocoumarol.
Alpha-1-proteinase inhibitorAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Nonacog beta pegol.
AlteplaseThe therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Alteplase.
Aminocaproic acidThe risk or severity of adverse effects can be increased when Aminocaproic acid is combined with Nonacog beta pegol.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RebinynPowder, for solution1000 unit / vialIntravenousNovo Nordisk2018-03-23Not applicableCanada flag
RebinynPowder, for solution3000 unit / vialIntravenousNovo Nordisk2024-02-13Not applicableCanada flag
RebinynPowder, for solution500 unit / vialIntravenousNovo Nordisk2018-03-23Not applicableCanada flag
RebinynPowder, for solution2000 unit / vialIntravenousNovo Nordisk2018-03-23Not applicableCanada flag
RefixiaInjection, powder, for solution3000 IUIntravenousNovo Nordisk2023-02-08Not applicableEU flag

Categories

Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
27Y83O992Q
CAS number
1175512-71-6

References

General References
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. Konkle B., Huston H. and Fletcher S. (2017). Gene Reviews. University of Washington..
  7. Globe Newswire News Release: Novo Nordisk receives US FDA approval of REBINYN® (nonacog beta pegol; N9-GP) [Link]
  8. FDA Blood Products Advisory Committee: Coagulation Factor IX (Recombinant), GlycoPEGylated N9-GP (nonacog beta pegol)_Meeting Briefing Document (April 4, 2017) [Link]
  9. FDA Blood Products Advisory Committee: BLA 125611_FDA Briefing Document (April 4, 2017) [Link]
  10. EMA Assessment Report: Refixia, INN-nonacog beta pegol [Link]
  11. DailyMed Label: REBINYN [Coagulation Factor IX (Recombinant), GlycoPEGylated] lyophilized powder for solution for intravenous injection [Link]
  12. Health Canada Product Monograph: REBINYN (nonacog beta pegol) Intravenous injection [Link]
  13. Summary of Product Characteristics: Refixia (nonacog beta pegol) intravenous injection [Link]
  14. Health Canada Approved Drug Products: REBINYN (nonacog beta pegol) Lyophilized powder for solution, intravenous (October 2022) [Link]
RxNav
1990855
Wikipedia
Factor_IX

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentHemophilia B1
3CompletedTreatmentCongenital Hematological Disorder / Hemophilia B5
1CompletedTreatmentCongenital Hematological Disorder / Hemophilia B1
Not AvailableCompletedNot AvailableHemophilia1
Not AvailableEnrolling by InvitationNot AvailableHemophilia B2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Powder, for solutionIntravenous1000 unit / vial
Powder, for solutionIntravenous2000 unit / vial
Powder, for solutionIntravenous3000 unit / vial
Powder, for solutionIntravenous500 unit / vial
Injection, powder, for solutionIntravenous1000 IU
Injection, powder, for solutionIntravenous2000 IU
Injection, powder, for solutionIntravenous3000 IU
Injection, powder, for solutionIntravenous500 IU
SolutionIntravenous1000 UI
Injection, solution1000 iu
Injection, powder, lyophilized, for solutionIntravenous1000 IU
Injection, solution2000 iu
Injection, solution500 iu
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySolubleBolourchian N., et al. 12(Suppl): 11-20. (2013)

Targets

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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
  1. 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
  1. FDA Blood Products Advisory Committee: Coagulation Factor IX (Recombinant), GlycoPEGylated N9-GP (nonacog beta pegol)_Meeting Briefing Document (April 4, 2017) [Link]
  2. 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
  1. FDA Blood Products Advisory Committee: Coagulation Factor IX (Recombinant), GlycoPEGylated N9-GP (nonacog beta pegol)_Meeting Briefing Document (April 4, 2017) [Link]
  2. 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