Identification

Summary

Damoctocog alfa pegol is a recombinant Factor VIII used to treat hemophilia A to control bleeding, perioperative bleeding, and also for prophylaxis of bleeding.

Brand Names
Jivi
Generic Name
Damoctocog alfa pegol
DrugBank Accession Number
DB14700
Background

In recent years, various extended half-life factor VIII and factor IX preparations have been studied and gained approval. In order to extend half-lives, techniques such as fusion to protein conjugates (Fc part of IgG1 or albumin), chemical modification (PEGylation), and protein sequence modification have been utilized.1

Also known as, BAY94-9027, Damoctocog alfa pegol is a longer-acting Factor VIII therapy formulated with polyethylene glycol (PEG) to reduce the number of infusions necessary to prevent bleeds in patients diagnosed with Haemophilia A.8,3,Label This product has been engineered by Bayer8 and a biological license application has been filed with the FDA in August 2017 and FDA approved in August 2018.13

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Blood factors
Protein Chemical Formula
Not Available
Protein Average Weight
234.0 Da (calculated average molecular weight)
Sequences
Not Available
Synonyms
  • Damoctocog alfa pegol

Pharmacology

Indication

Indicated for use in previously treated adults and adolescents (12 years of age and above) with hemophilia A (congenital Factor VIII deficiency) for:

On-demand treatment and control of bleeding episodes Label, perioperative management of bleeding Label, and routine prophylaxis to reduce the frequency of bleeding episodes Label.

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

This agent is engineered to prolong blood FVIII activity while maintaining coagulation activity using PEGylation, where a PEG (Polyethylene glycol) molecule is continually attached to the factor VIII protein at a specific site 8, 3. This prevents and controls bleeding episodes associated with hemophilia A.

The aPTT is prolonged in people diagnosed with hemophilia A. The determination of aPTT is a conventional in vitro assay for assessing the biological activity of Factor VIII. Treatment with damoctogog alfa pegol normalizes the aPTT similar to that achieved with plasma-derived Factor VIII. The administration of this agent increases plasma levels of Factor VIII and can temporarily correct the coagulation defect that exists in hemophilia A patients Label.

Mechanism of action

This drug is a site-specifically PEGylated recombinant antihemophilic factor, which temporarily replaces the missing coagulation Factor VIII. The site-specific PEGylation in the A3 domain reduces binding to the physiological Factor VIII clearance receptors resulting in a longer half-life and increased AUC (area under the curve) Label.

The active protein, prior to conjugation is a recombinant B-domain deleted human coagulation Factor VIII (BDD-rFVIII) produced by recombinant DNA technology in Baby Hamster Kidney (BHK) cells Label.

Damoctagol alfa pegol is manufactured by site-specific conjugation of the BDD-rFVIII variant K1804C at the cysteine amino acid position 1804 (within the A3 domain) with a single maleimide-derivatized, 60 kilodalton (kDa) branched PEG (two 30 kDa PEG) moiety. The A3 domain was identified and selected for conjugation to provide both a continual coagulation activity and high PEGylation efficiency Label.

TargetActionsOrganism
ACoagulation factor VIII
binder
Humans
Absorption

After a single dose, AUC (area under the curve) was 1640 ± 550 Label with a dose of 25 IU/kg.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

18.6 ± 4.6h after a single dose Label

Clearance

142 ± 33 mL/h on with a dose of 25 IU/kg and 121 ± 53 mL/h with a dose of 60 IU/kg Label.

Adverse Effects
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Toxicity

The most commonly reported adverse reactions in clinical trials in previously treated patients (PTPs) ≥ 12 years of age (≥ 5%) were headache, cough, nausea, and fever Label.

Hypersensitivity reactions, which includes severe allergic reactions, have occurred. Monitor patients for hypersensitivity symptoms. Should hypersensitivity symptoms occur, stop treatment with this agent and administer appropriate supportive treatment. Hypersensitivity reactions may also be related to antibodies targeted against polyethylene glycol (PEG) Label.

Development of Factor VIII neutralizing antibodies can also occur. If expected plasma Factor VIII activity levels are not reached, or if bleeding is not controlled as expected with the administered dose, perform an assay that quantifies Factor VIII inhibitor concentration Label.

Immune response to PEG, manifested as symptoms of acute hypersensitivity and/or loss of drug effect, has been observed mainly in subjects less than 6 years of age. Evaluate patients experiencing symptoms of hypersensitivity reactions in the absence of detectable Factor VIII inhibitors for possible bleeding or impaired recovery 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.
DrugInteraction
AbciximabThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Abciximab.
AcenocoumarolThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Acenocoumarol.
Alpha-1-proteinase inhibitorAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Damoctocog alfa pegol.
AlteplaseThe therapeutic efficacy of Damoctocog alfa 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 Damoctocog alfa pegol.
AncrodThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Ancrod.
AnistreplaseThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Anistreplase.
Antihemophilic factor (recombinant), PEGylatedThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Antihemophilic factor (recombinant), PEGylated.
Antithrombin AlfaThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Antithrombin Alfa.
Antithrombin III humanThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Antithrombin III human.
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
JiviInjection, powder, for solution250 IUIntravenousBayer Ag2021-01-12Not applicableEU flag
JiviPowder, for solution1000 unit / vialIntravenousBayer2020-03-11Not applicableCanada flag
JiviInjection, powder, for solution2000 IUIntravenousBayer Ag2021-01-12Not applicableEU flag
JiviSolution3000 [iU]/2.5mLIntravenousBayer HealthCare LLC2018-08-30Not applicableUS flag
JiviInjection, powder, for solution250 IUIntravenousBayer Ag2021-01-12Not applicableEU flag
JiviInjection, powder, for solution1000 IUIntravenousBayer Ag2021-01-12Not applicableEU flag
JiviSolution500 [iU]/2.5mLIntravenousBayer HealthCare LLC2018-08-30Not applicableUS flag
JiviPowder, for solution3000 unit / vialIntravenousBayer2020-01-27Not applicableCanada flag
JiviPowder, for solution500 unit / vialIntravenousBayer2020-04-08Not applicableCanada flag
JiviInjection, powder, for solution1000 IUIntravenousBayer Ag2021-01-12Not applicableEU flag

Categories

Drug Categories
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
  • Humans and other mammals

Chemical Identifiers

UNII
BY4TSK952Y
CAS number
1363853-26-2

References

General References
  1. Graf L: Extended Half-Life Factor VIII and Factor IX Preparations. Transfus Med Hemother. 2018 Apr;45(2):86-91. doi: 10.1159/000488060. Epub 2018 Mar 21. [Article]
  2. Morfini M, Gherardini S: Pharmacokinetic-based prediction of real-life dosing of extended half-life clotting factor concentrates on hemophilia. Ther Adv Hematol. 2018 Jun;9(6):149-162. doi: 10.1177/2040620718774258. Epub 2018 Jun 5. [Article]
  3. Hartmann J, Croteau SE: 2017 Clinical trials update: Innovations in hemophilia therapy. Am J Hematol. 2016 Dec;91(12):1252-1260. doi: 10.1002/ajh.24543. Epub 2016 Oct 3. [Article]
  4. Coyle TE, Reding MT, Lin JC, Michaels LA, Shah A, Powell J: Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A. J Thromb Haemost. 2014 Apr;12(4):488-96. [Article]
  5. Schulte S: Innovative coagulation factors: albumin fusion technology and recombinant single-chain factor VIII. Thromb Res. 2013 Mar;131 Suppl 2:S2-6. doi: 10.1016/S0049-3848(13)70150-6. [Article]
  6. Klamroth R, Simpson M, von Depka-Prondzinski M, Gill JC, Morfini M, Powell JS, Santagostino E, Davis J, Huth-Kuhne A, Leissinger C, Neumeister P, Bensen-Kennedy D, Feussner A, Limsakun T, Zhou M, Veldman A, St Ledger K, Blackman N, Pabinger I: Comparative pharmacokinetics of rVIII-SingleChain and octocog alfa (Advate((R)) ) in patients with severe haemophilia A. Haemophilia. 2016 Sep;22(5):730-8. doi: 10.1111/hae.12985. Epub 2016 Jul 19. [Article]
  7. Mei B, Pan C, Jiang H, Tjandra H, Strauss J, Chen Y, Liu T, Zhang X, Severs J, Newgren J, Chen J, Gu JM, Subramanyam B, Fournel MA, Pierce GF, Murphy JE: Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment. Blood. 2010 Jul 15;116(2):270-9. doi: 10.1182/blood-2009-11-254755. Epub 2010 Mar 1. [Article]
  8. Pharmatimes: Bayer files long-acting haemophilia therapy in the US [Link]
  9. A Trial Investigating Safety and Efficacy of Treatment With BAY94-9027 in Severe Hemophilia A (PROTECT-VIII) [Link]
  10. EMA: Damoctagog Alfa [Link]
  11. World Health Organization Document [File]
  12. Extended Half-Life Factor VIII and Factor IX Preparations [File]
  13. BLA, Damoctacog alfa peg, August 2018 [File]
RxNav
2055655
Wikipedia
Damoctocog_alfa_pegol
FDA label
Download (503 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentHemophilia As1
4Not Yet RecruitingTreatmentHemophilia As / Prophylaxis of Bleeding1
3RecruitingTreatmentChildren / Hemophilia As / Prophylaxis of Bleeding / Treatment of Bleeding1
1CompletedBasic ScienceHemophilia As1
1CompletedTreatmentHemophilia As1
Not AvailableCompletedNot AvailableHemophilia As1
Not AvailableRecruitingNot AvailableHemophilia As3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous1000 IU
Injection, powder, for solutionIntravenous2000 IU
Injection, powder, for solutionIntravenous250 IU
Injection, powder, for solutionIntravenous3000 IU
Injection, powder, for solutionIntravenous500 IU
Powder, for solutionIntravenous1000 unit / vial
Powder, for solutionIntravenous2000 unit / vial
Powder, for solutionIntravenous250 unit / vial
Powder, for solutionIntravenous3000 unit / vial
Powder, for solutionIntravenous500 unit / vial
SolutionIntravenous1000 [iU]/2.5mL
SolutionIntravenous2000 [iU]/5mL
SolutionIntravenous3000 [iU]/2.5mL
SolutionIntravenous500 [iU]/2.5mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
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. Graf L: Extended Half-Life Factor VIII and Factor IX Preparations. Transfus Med Hemother. 2018 Apr;45(2):86-91. doi: 10.1159/000488060. Epub 2018 Mar 21. [Article]
  2. Morfini M, Gherardini S: Pharmacokinetic-based prediction of real-life dosing of extended half-life clotting factor concentrates on hemophilia. Ther Adv Hematol. 2018 Jun;9(6):149-162. doi: 10.1177/2040620718774258. Epub 2018 Jun 5. [Article]
  3. Klamroth R, Simpson M, von Depka-Prondzinski M, Gill JC, Morfini M, Powell JS, Santagostino E, Davis J, Huth-Kuhne A, Leissinger C, Neumeister P, Bensen-Kennedy D, Feussner A, Limsakun T, Zhou M, Veldman A, St Ledger K, Blackman N, Pabinger I: Comparative pharmacokinetics of rVIII-SingleChain and octocog alfa (Advate((R)) ) in patients with severe haemophilia A. Haemophilia. 2016 Sep;22(5):730-8. doi: 10.1111/hae.12985. Epub 2016 Jul 19. [Article]
  4. Mei B, Pan C, Jiang H, Tjandra H, Strauss J, Chen Y, Liu T, Zhang X, Severs J, Newgren J, Chen J, Gu JM, Subramanyam B, Fournel MA, Pierce GF, Murphy JE: Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment. Blood. 2010 Jul 15;116(2):270-9. doi: 10.1182/blood-2009-11-254755. Epub 2010 Mar 1. [Article]

Drug created at September 13, 2018 17:56 / Updated at June 03, 2022 07:24