Identification
- Summary
Turoctocog alfa is an antihemorrhagic agent used for the treatment and prophylaxis of bleeding in patients of all ages with haemophilia A (congenital factor VIII deficiency).
- Brand Names
- Novoeight, Zonovate
- Generic Name
- Turoctocog alfa
- DrugBank Accession Number
- DB09109
- Background
Turoctocog alfa is a recombinant factor VIII (rFVIII) with a truncated B-domain made from the sequence coding for 10 amino acids from the N-terminus and 11 amino acids from the C-terminus of the naturally occurring B-domain. Turoctocog alfa is produced in Chinese hamster ovary (CHO) cells without addition of any human- or animal-derived materials. During secretion, some rFVIII molecules are cleaved at the C-terminal of the heavy chain (HC) at amino acid 720, and a monoclonal antibody binding C-terminal to this position is used in the purification process allowing isolation of the intact rFVIII.1 It was developped by Novo Nordisk and FDA approved in October 16, 2013.6
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Blood factors - Protein Structure
- Protein Chemical Formula
- C7480H11379N1999O2194S68
- Protein Average Weight
- 166000.0 Da (Without post-translational modifications)
- Sequences
>>Heavy chain<<< ATRRYYLGAVELSWDYMQSDLGELPVDARFPPRVPKSFPFNTSVVYKKTLFVEFTDHLFN IAKPRPPWMGLLGPTIQAEVYDTVVITLKNMASHPVSLHAVGVSYWKASEGAEYDDQTSQ REKEDDKVFPGGSHTYVWQVLKENGPMASDPLCLTYSYLSHVDLVKDLNSGLIGALLVCR EGSLAKEKTQTLHKFILLFAVFDEGKSWHSETKNSLMQDRDAASARAWPKMHTVNGYVNR SLPGLIGCHRKSVYWHVIGMGTTPEVHSIFLEGHTFLVRNHRQASLEISPITFLTAQTLL MDLGQFLLFCHISSHQHDGMEAYVKVDSCPEEPQLRMKNNEEAEDYDDDLTDSEMDVVRF DDDNSPSFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLAPDDRSYKSQYLNNGPQRIG RKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTLLIIFKNQASRPYNIYPHGI TDVRPLYSRRLPKGVKHLKDFPILPGEIFKYKWTVTVEDGPTKSDPRCLTRYYSSFVNME RDLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDENRSWYLTENIQRFLPNPAG VQLEDPEFQASNIMHSINGYVFDSLQLSVCLHEVAYWYILSIGAQTDFLSVFFSGYTFKH KMVYEDTLTLFPFSGETVFMSMENPGLWILGCHNSDFRNRGMTALLKVSSCDKNTGDYYE DSYEDISAYLLSKNNAIEPRSFSQNSRHPSQNPPVLKRHQR
>>Light chain<<< EITRTTLQSDQEEIDYDDTISVEMKKEDFDIYDEDENQSPRSFQKKTRHYFIAAVERLWD YGMSSSPHVLRNRAQSGSVPQFKKVVFQEFTDGSFTQPLYRGELNEHLGLLGPYIRAEVE DNIMVTFRNQASRPYSFYSSLISYEEDQRQGAEPRKNFVKPNETKTYFWKVQHHMAPTKD EFDCKAWAYFSDVDLEKDVHSGLIGPLLVCHTNTLNPAHGRQVTVQEFALFFTIFDETKS WYFTENMERNCRAPCNIQMEDPTFKENYRFHAINGYIMDTLPGLVMAQDQRIRWYLLSMG SNENIHSIHFSGHVFTVRKKEEYKMALYNLYPGVFETVEMLPSKAGIWRVECLIGEHLHA GMSTLFLVYSNKCQTPLGMASGHIRDFQITASGQYGQWAPKLARLHYSGSINAWSTKEPF SWIKVDLLAPMIIHGIKTQGARQKFSSLYISQFIIMYSLDGKKWQTYRGNSTGTLMVFFG NVDSSGIKHNIFNPPIIARYIRLHPTHYSIRSTLRMELMGCDLNSCSMPLGMESKAISDA QITASSYFTNMFATWSPSKARLHLQGRSNAWRPQVNNPKEWLQVDFQKTMKVTGVTTQGV KSLLTSMYVKEFLISSSQDGHQWTLFFQNGKVKVFQGNQDSFTPVVNSLDPPLLTRYLRI HPQSWVHQIALRMEVLGCEAQDLY
Download FASTA Format- Synonyms
- Turoctocog alfa
Pharmacology
- Indication
Turoctocog alfa is indicated for the treatment and prophylaxis of bleedings in patients presenting hemophilia A.7 The treatment with turoctocog alfa is related with its use to control bleeding episodes or as a perioperative management.8 Hemophilia A is a hereditary hemorrhagic disorder generated by the congenital deficit of the coagulation factor VIII. This disease is manifested as excessive spontaneous or trauma-driven bleeding. The coagulation factor VIII is a robust initiator of thrombin which is later required for the generation of fibrin to form a platelet plug and its gene is expressed in the X chromosome.2
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- Contraindications & Blackbox Warnings
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After turoctocog alfa administration, it has been reported a significant improvement in hemostasis. This effect was observed by the amelioration on whole blood clotting time.3 In clinical trials, there were no reports of development of factor VIII inhibitors and even 90% of the ocurred bleeds were resolved with 1 or 2 infusions of turoctocog alfa. There are no reports of treatment failure.9 In vitro studies confirmed the ability of turoctocog alfa to improve clot formation and clot stability. All these studies prove that turoctocog alfa is fully functional and its activity is similar to the one showed by other recombinant factor VIII products.10
- Mechanism of action
The B domain is known to perform the function of restrict the expression of the endogenous coagulation factor VIII but it has no direct relationship to the function of this factor. In normal conditions during hemostasis, the coagulation factor VIII will be activated by specific thrombin cleavages producing A1, A2 and A3-C1-C2 fragments of activated factor VIII (Factor VIIIa) which will form a complex with the factor IXa and activate the factor X leading to a stable haemostatic plug.1 Turoctocog contains all function-related domains with a considerably easier intact expression of the protein in mammalian cells by truncating the B domain.4 This recombinant structure allows it to replace the missing factor VIII and restore hemostasis.7
Target Actions Organism ACoagulation factor IX activatorHumans ACoagulation factor X activatorHumans AProthrombin binderHumans - Absorption
In pre-clinical studies, the absorption half-life was reported wot be 5.4 hours.3 The absorption profile varies depending on the age of the patient where the AUC is 9.92, 11.09 and 15.26 IU hour/ml for the age range of 0-6 years, 6-12 years and over 12 years old respectively. The Cmax according to the different age groups is 1, 1.07 and 1.226 IU/ml for the age range of 0-6 years, 6-12 years and over 12 years old respectively.9
- Volume of distribution
In pre-clinical studies, turoctocog distribution was studied based on a two model compartment and it resulted in 59 ml/kg in the central compartment and 13 ml/kg in the peripheral compartment. It also presented an inter-compartmental flow of 0.66 ml/hour kg.3
- Protein binding
Because turoctocog alfa is a recombinant protein, there has been not enough studies of protein binding.10
- Metabolism
Turoctocog alfa is expected to be cleaved by proteolysis into small individual aminoacids that constitute them after receptor mediated cell endocytosis.10
- Route of elimination
After intravenous administration of turoctocog alfa, the time for complete elimination of the blood plasma is of 50-55 hours. Due to the fact that this drug is a 166 kDa, it is thought that it will be eliminated by tissue mechanisms such as receptor mediated endocytosis followed by catabolism rather than hepatic metabolism and renal excretion.10
- Half-life
In pre-clinical studies, turoctocog half-life was reported to be 16 hours.3 In knockout mice there are reports of half-life of 7-8 hours.10
- Clearance
In pre-clinical studies, turoctocog clearance was reported to be 6.5 ml/hour kg.3
- Adverse Effects
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In preclinical safety studies, there was a change in reported systolic pressure after 2-weeks of multiple dosing.9 Thrombus formation, cardiovascular, neurological or respiratory effects are not expected to be a safety concern.10
- 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 Turoctocog alfa can be decreased when used in combination with Abciximab. Acenocoumarol The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Acenocoumarol. Alpha-1-proteinase inhibitor Alpha-1-proteinase inhibitor may increase the thrombogenic activities of Turoctocog alfa. Alteplase The therapeutic efficacy of Turoctocog alfa 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 Turoctocog alfa. - 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 Novoeight Injection, powder, for solution 2000 IU Intravenous Novo Nordisk 2016-09-08 Not applicable EU 
Novoeight Injection, powder, for solution 500 IU Intravenous Novo Nordisk 2016-09-08 Not applicable EU Novoeight Injection, powder, for solution 1500 IU Intravenous Novo Nordisk 2016-09-08 Not applicable EU Novoeight Injection, powder, for solution 250 IU Intravenous Novo Nordisk 2016-09-08 Not applicable EU Novoeight Injection, powder, for solution 3000 IU Intravenous Novo Nordisk 2016-09-08 Not applicable EU
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
- 969NZA3X9T
- CAS number
- 1192451-26-5
References
- General References
- Ezban M, Vad K, Kjalke M: Turoctocog alfa (NovoEight(R))--from design to clinical proof of concept. Eur J Haematol. 2014 Nov;93(5):369-76. doi: 10.1111/ejh.12366. Epub 2014 May 28. [Article]
- Salen P, Babiker HM: Hemophilia A . [Article]
- Agerso H, Stennicke HR, Pelzer H, Olsen EN, Merricks EP, Defriess NA, Nichols TC, Ezban M: Pharmacokinetics and pharmacodynamics of turoctocog alfa and N8-GP in haemophilia A dogs. Haemophilia. 2012 Nov;18(6):941-7. doi: 10.1111/j.1365-2516.2012.02896.x. Epub 2012 Jul 20. [Article]
- Ahmadian H, Hansen EB, Faber JH, Sejergaard L, Karlsson J, Bolt G, Hansen JJ, Thim L: Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule. Blood Coagul Fibrinolysis. 2016 Jul;27(5):568-75. doi: 10.1097/MBC.0000000000000477. [Article]
- Takedani H, Hirose J: Turoctocog alfa: an evidence-based review of its potential in the treatment of hemophilia A. Drug Des Devel Ther. 2015 Mar 24;9:1767-72. doi: 10.2147/DDDT.S57967. eCollection 2015. [Article]
- FiercePharma [Link]
- EMA Reports [Link]
- NovoNordisk [Link]
- EU Reports [Link]
- Australian report [Link]
- External Links
- PubChem Substance
- 347910410
- 1737557
- Wikipedia
- Turoctocog_alfa
- MSDS
- Download (269 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Congenital Hematological Disorder / Hemophilia A 1 3 Completed Treatment Congenital Hematological Disorder / Hemophilia A 5 3 Terminated Treatment Hemophilia A 1 2 Completed Treatment Hemophilia A / Hemostasis 1 1 Completed Treatment Congenital Hematological Disorder / Hemophilia A 5
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Intravenous 500 UI Injection, powder, for solution Intravenous Injection, powder, for solution Intravenous 1500 IU Injection, powder, for solution Intravenous 2000 IU Injection, powder, for solution Intravenous 3000 IU Solution Intravenous 250.00 UI Injection, powder, for solution Parenteral 1000 iu Injection, powder, for solution Parenteral 1500 iu Injection, powder, for solution Parenteral 2000 iu Injection, powder, for solution Parenteral 250 iu Injection, powder, for solution Parenteral 3000 iu Injection, powder, for solution Parenteral 500 iu Injection, powder, for solution Intravenous 1000 IU Injection, powder, for solution Intravenous 250 IU Injection, powder, for solution Intravenous 500 IU Injection, powder, lyophilized, for solution Intravenous 1500 IU Injection, powder, lyophilized, for solution Intravenous 150000000 IU Injection, powder, lyophilized, for solution Intravenous 200000000 IU Injection, powder, lyophilized, for solution Intravenous 25000000 IU Injection, powder, lyophilized, for solution Intravenous 3000 IU Injection, powder, for solution Intravenous 100000000 IU Injection, powder, lyophilized, for solution Intravenous 50000000 IU Kit; powder, for solution Intravenous 1000 unit / vial Kit; powder, for solution Intravenous 1500 unit / vial Kit; powder, for solution Intravenous 2000 unit / vial Kit; powder, for solution Intravenous 250 unit / vial Kit; powder, for solution Intravenous 3000 unit / vial Kit; powder, for solution Intravenous 500 unit / vial Injection, powder, for solution 250 IU Injection, powder, for solution 500 IU - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source water solubility Soluble NovoNordisk monograph isoelectric point It does not posses a distinct value NovoNordisk monograph
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Serine-type endopeptidase activity
- Specific Function
- Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholi...
- Gene Name
- F9
- Uniprot ID
- P00740
- Uniprot Name
- Coagulation factor IX
- Molecular Weight
- 51778.11 Da
References
- Ezban M, Vad K, Kjalke M: Turoctocog alfa (NovoEight(R))--from design to clinical proof of concept. Eur J Haematol. 2014 Nov;93(5):369-76. doi: 10.1111/ejh.12366. Epub 2014 May 28. [Article]
- Ahmadian H, Hansen EB, Faber JH, Sejergaard L, Karlsson J, Bolt G, Hansen JJ, Thim L: Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule. Blood Coagul Fibrinolysis. 2016 Jul;27(5):568-75. doi: 10.1097/MBC.0000000000000477. [Article]
- EMA Reports [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- 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
- Ezban M, Vad K, Kjalke M: Turoctocog alfa (NovoEight(R))--from design to clinical proof of concept. Eur J Haematol. 2014 Nov;93(5):369-76. doi: 10.1111/ejh.12366. Epub 2014 May 28. [Article]
- Ahmadian H, Hansen EB, Faber JH, Sejergaard L, Karlsson J, Bolt G, Hansen JJ, Thim L: Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule. Blood Coagul Fibrinolysis. 2016 Jul;27(5):568-75. doi: 10.1097/MBC.0000000000000477. [Article]
- EMA Reports [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Thrombospondin receptor activity
- Specific Function
- Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
- Gene Name
- F2
- Uniprot ID
- P00734
- Uniprot Name
- Prothrombin
- Molecular Weight
- 70036.295 Da
References
- Australian report [Link]
Drug created at September 17, 2015 21:07 / Updated at June 03, 2022 07:24