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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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Hemophilia as •••••••••••• ••••••••••• ••••• •••••••••• ••••••• ••••••••• - Contraindications & Blackbox Warnings
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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.
Target Actions Organism ACoagulation factor VIII binderHumans - 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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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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Abciximab. Acenocoumarol The therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Acenocoumarol. Alpha-1-proteinase inhibitor Alpha-1-proteinase inhibitor may increase the thrombogenic activities of Damoctocog alfa pegol. Alteplase The therapeutic efficacy of Damoctocog alfa 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 Damoctocog alfa 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 Jivi Injection, powder, for solution 250 IU Intravenous Bayer Ag 2021-01-12 Not applicable EU 
Jivi Injection, powder, for solution 250 IU Intravenous Bayer Ag 2021-01-12 Not applicable EU Jivi Powder, for solution 1000 unit / vial Intravenous Bayer 2020-03-11 Not applicable Canada 
Jivi Injection, powder, lyophilized, for solution; Kit 3000 [iU]/2.5mL Intravenous Bayer HealthCare LLC 2018-08-30 Not applicable US 
Jivi Injection, powder, lyophilized, for solution; Kit 500 [iU]/2.5mL Intravenous Bayer HealthCare LLC 2018-08-30 Not applicable US
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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Pharmatimes: Bayer files long-acting haemophilia therapy in the US [Link]
- A Trial Investigating Safety and Efficacy of Treatment With BAY94-9027 in Severe Hemophilia A (PROTECT-VIII) [Link]
- EMA: Damoctagog Alfa [Link]
- World Health Organization Document [File]
- Extended Half-Life Factor VIII and Factor IX Preparations [File]
- BLA, Damoctacog alfa peg, August 2018 [File]
- External Links
- 2055655
- Wikipedia
- Damoctocog_alfa_pegol
- FDA label
- Download (503 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Hemophilia A 1 4 Recruiting Treatment Hemophilia A / Prophylaxis of Bleeding 1 3 Active Not Recruiting Treatment Children / Hemophilia A / Prophylaxis of Bleeding / Treatment of Bleeding 1 1 Completed Basic Science Hemophilia A 1 1 Completed Treatment Hemophilia A 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 1000 IU Injection, powder, for solution Intravenous 2000 IU Injection, powder, for solution Intravenous 250 IU Injection, powder, for solution Intravenous 3000 IU Injection, powder, for solution Intravenous 500 IU Injection, powder, lyophilized, for solution; kit Intravenous 1000 [iU]/2.5mL Injection, powder, lyophilized, for solution; kit Intravenous 2000 [iU]/5mL Injection, powder, lyophilized, for solution; kit Intravenous 3000 [iU]/2.5mL Injection, powder, lyophilized, for solution; kit Intravenous 500 [iU]/2.5mL Powder, for solution Intravenous 1000 unit / vial Powder, for solution Intravenous 2000 unit / vial Powder, for solution Intravenous 250 unit / vial Powder, for solution Intravenous 3000 unit / vial Powder, for solution Intravenous 500 unit / vial - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- 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
- 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]
- 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]
- 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]
- 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