Damoctocog alfa pegol

Identification

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Name
Damoctocog alfa pegol
Accession Number
DB14700
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Blood factors
Description

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

Protein chemical formula
Not Available
Protein average weight
234.0 Da (calculated average molecular weight)
Sequences
Not Available
Synonyms
  • Damoctocog alfa pegol
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
JiviKit3000 [iU]/2.5mLIntravenousBayer HealthCare LLC2018-08-30Not applicableUs
JiviKit2000 [iU]/5mLIntravenousBayer HealthCare LLC2018-08-30Not applicableUs
JiviPowder, for solution3000 unitIntravenousBayerNot applicableNot applicableCanada
JiviKit1000 [iU]/2.5mLIntravenousBayer HealthCare LLC2018-08-30Not applicableUs
JiviPowder, for solution2000 unitIntravenousBayerNot applicableNot applicableCanada
JiviPowder, for solution500 unitIntravenousBayerNot applicableNot applicableCanada
JiviKit500 [iU]/2.5mLIntravenousBayer HealthCare LLC2018-08-30Not applicableUs
JiviPowder, for solution1000 unitIntravenousBayerNot applicableNot applicableCanada
JiviPowder, for solution250 unitIntravenousBayerNot applicableNot applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

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Categories
UNII
BY4TSK952Y
CAS number
1363853-26-2

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.

Associated Conditions
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
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

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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.

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.

Affected organisms
  • Humans and other mammals
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
(R)-warfarinThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with (R)-warfarin.
(S)-WarfarinThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with (S)-Warfarin.
4-hydroxycoumarinThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with 4-hydroxycoumarin.
AbciximabThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Abciximab.
Abicipar PegolThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Abicipar Pegol.
AcenocoumarolThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Acenocoumarol.
Acetylsalicylic acidThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Acetylsalicylic acid.
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.
AmediplaseThe therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Amediplase.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
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Food Interactions
Not Available

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. [PubMed:29765290]
  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. [PubMed:29899890]
  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. [PubMed:27563744]
  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. [PubMed:24843882]
  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. [PubMed:23537723]
  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. [PubMed:27434619]
  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. [PubMed:20194895]
  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]
External Links
Not Available
FDA label
Download (503 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHemophilia A1
1RecruitingTreatmentHemophilia A1
4Not Yet RecruitingTreatmentHemophilia A1
Not AvailableNot Yet RecruitingNot AvailableHemophilia A2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
KitIntravenous1000 [iU]/2.5mL
KitIntravenous2000 [iU]/5mL
KitIntravenous3000 [iU]/2.5mL
KitIntravenous500 [iU]/2.5mL
Powder, for solutionIntravenous1000 unit
Powder, for solutionIntravenous2000 unit
Powder, for solutionIntravenous250 unit
Powder, for solutionIntravenous3000 unit
Powder, for solutionIntravenous500 unit
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

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

Targets

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. [PubMed:29765290]
  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. [PubMed:29899890]
  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. [PubMed:27434619]
  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. [PubMed:20194895]

Drug created on September 13, 2018 11:56 / Updated on September 02, 2019 20:21