Identification

Name
Vonicog Alfa
Accession Number
DB12872
Description

Vonicog Alfa is a recombinant von Willebrand factor manufactured by Baxalta. It was FDA approved in December 2015.1 The gen of von Willebrand factor was first cloned in 1985 by Stuart Orkin and David Ginsburg.6 By the EMA, vonicog alfa is still under clinical analysis.7

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Blood factors
Protein Structure
Db12872
Protein Chemical Formula
Not Available
Protein Average Weight
20000000.0 Da (Contains all multimers and ultra-large multimers)
Sequences
>>von Willebrand factor<<<
MIPARFAGVLLALALILPGTLCAEGTRGRSSTARCSLFGSDFVNTFDGSMYSFAGYCSYL
AGGCQKRSFSIIGDFQNGKRVSLSVYLGEFFDIHLFVNGTVTQGDQRVSMPYASKGLYLE
TEAGYYKLSGEAYGFVARIDGSGNFQVLLSDRYFNKTCGLCGNFNIFAEDDFMTQEGTLT
SDPYDFANSWALSSGEQWCERASPPSSSCNISSGEMQKGLWEQCQLLKSTSVFARCHPLV
DPEPFVALCEKTLCECAGGLECACPALLEYARTCAQEGMVLYGWTDHSACSPVCPAGMEY
RQCVSPCARTCQSLHINEMCQERCVDGCSCPEGQLLDEGLCVESTECPCVHSGKRYPPGT
SLSRDCNTCICRNSQWICSNEECPGECLVTGQSHFKSFDNRYFTFSGICQYLLARDCQDH
SFSIVIETVQCADDRDAVCTRSVTVRLPGLHNSLVKLKHGAGVAMDGQDIQLPLLKGDLR
IQHTVTASVRLSYGEDLQMDWDGRGRLLVKLSPVYAGKTCGLCGNYNGNQGDDFLTPSGL
AEPRVEDFGNAWKLHGDCQDLQKQHSDPCALNPRMTRFSEEACAVLTSPTFEACHRAVSP
LPYLRNCRYDVCSCSDGRECLCGALASYAAACAGRGVRVAWREPGRCELNCPKGQVYLQC
GTPCNLTCRSLSYPDEECNEACLEGCFCPPGLYMDERGDCVPKAQCPCYYDGEIFQPEDI
FSDHHTMCYCEDGFMHCTMSGVPGSLLPDAVLSSPLSHRSKRSLSCRPPMVKLVCPADNL
RAEGLECTKTCQNYDLECMSMGCVSGCLCPPGMVRHENRCVALERCPCFHQGKEYAPGET
VKIGCNTCVCRDRKWNCTDHVCDATCSTIGMAHYLTFDGLKYLFPGECQYVLVQDYCGSN
PGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNVKRPMKDETHFEVVESGRY
IILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVEEDPVDF
GNSWKVSSQCADTRKVPLDSSPATCHNNIMKQTMVDSSCRILTSDVFQDCNKLVDPEPYL
DVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTATLCPQSCEERNLRENGYE
CEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKILDELLQTCVDPEDCPVCEV
AGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEPGGLVVPPTDAPVSPTTLYVED
ISEPPLHDFYCSRLLDLVFLLDGSSRLSEAEFEVLKAFVVDMMERLRISQKWVRVAVVEY
HDGSHAYIGLKDRKRPSELRRIASQVKYAGSQVASTSEVLKYTLFQIFSKIDRPEASRIA
LLLMASQEPQRMSRNFVRYVQGLKKKKVIVIPVGIGPHANLKQIRLIEKQAPENKAFVLS
SVDELEQQRDEIVSYLCDLAPEAPPPTLPPHMAQVTVGPGLLGVSTLGPKRNSMVLDVAF
VLEGSDKIGEADFNRSKEFMEEVIQRMDVGQDSIHVTVLQYSYMVTVEYPFSEAQSKGDI
LQRVREIRYQGGNRTNTGLALRYLSDHSFLVSQGDREQAPNLVYMVTGNPASDEIKRLPG
DIQVVPIGVGPNANVQELERIGWPNAPILIQDFETLPREAPDLVLQRCCSGEGLQIPTLS
PAPDCSQPLDVILLLDGSSSFPASYFDEMKSFAKAFISKANIGPRLTQVSVLQYGSITTI
DVPWNVVPEKAHLLSLVDVMQREGGPSQIGDALGFAVRYLTSEMHGARPGASKAVVILVT
DVSVDSVDAAADAARSNRVTVFPIGIGDRYDAAQLRILAGPAGDSNVVKLQRIEDLPTMV
TLGNSFLHKLCSGFVRICMDEDGNEKRPGDVWTLPDQCHTVTCQPDGQTLLKSHRVNCDR
GLRPSCPNSQSPVKVEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVLFQNKE
QDLEVILHNGACSPGARQGCMKSIEVKHSALSVELHSDMEVTVNGRLVSVPYVGGNMEVN
VYGAIMHEVRFNHLGHIFTFTPQNNEFQLQLSPKTFASKTYGLCGICDENGANDFMLRDG
TVTTDWKTLVQEWTVQRPGQTCQPILEEQCLVPDSSHCQVLLLPLFAECHKVLAPATFYA
ICQQDSCHQEQVCEVIASYAHLCRTNGVCVDWRTPDFCAMSCPPSLVYNHCEHGCPRHCD
GNVSSCGDHPSEGCFCPPDKVMLEGSCVPEEACTQCIGEDGVQHQFLEAWVPDHQPCQIC
TCLSGRKVNCTTQPCPTAKAPTCGLCEVARLRQNADQCCPEYECVCDPVSCDLPPVPHCE
RGLQPTLTNPGECRPNFTCACRKEECKRVSPPSCPPHRLPTLRKTQCCDEYECACNCVNS
TVSCPLGYLASTATNDCGCTTTTCLPDKVCVHRSTIYPVGQFWEEGCDVCTCTDMEDAVM
GLRVAQCSQKPCEDSCRSGFTYVLHEGECCGRCLPSACEVVTGSPRGDSQSSWKSVGSQW
ASPENPCLINECVRVKEEVFIQQRNVSCPQLEVPVCPSGFQLSCKTSACCPSCRCERMEA
CMLNGTVIGPGKTVMIDVCTTCRCMVQVGVISGFKLECRKTTCNPCPLGYKEENNTGECC
GRCLPTACTIQLRGGQIMTLKRDETLQDGCDTHFCKVNERGEYFWEKRVTGCPPFDEHKC
LAEGGKIMKIPGTCCDTCEEPECNDITARLQYVKVGSCKSEVEVDIHYCQGKCASKAMYS
IDINDVQDQCSCCSPTRTEPMQVALHCTNGSVVYHEVLNAMECKCSPRKCSK
Download FASTA Format
Synonyms
  • Von willebrand factor (recombinant)
External IDs
  • BAX 111
  • BAX-111

Pharmacology

Indication

Vonicog alfa is indicated for the on-demand treatment and control of bleeding episodes in adults previously diagnosed with von Willebrand disease.8 Vonicog alfa contains only the vWF and thus, its administration offers the flexibility to administer the coagulation factor VIII if needed. The von Willebrand disease is an inherited disorder characterized by the deficiency or misfunction of the von Willebrand factor (vWF). Due to this deficiency, the blood cannot clot properly and the patients that present this disease are prone to prolonged or excessive bleeding. There are three types of this disease, and type 3 is an autosomal recessive inherited disorder marked by very low or absent levels of vWF.9

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Vonicog alfa does not present a risk of transmission of blood-borne pathogens as it is a recombinant, plasma- and albumin-free protein. The two first clinical trials showed an effective reduction of bleeding episodes in different sites of the body. This effect was observed even after the first infusion in 81% of the cases.3

Mechanism of action

Von Willebrand factor (vWF) is an important piece of the blood coagulation cascade and it acts by stabilizing the coagulation factor VIII. It also binds to collagen and platelets in blood vessel walls which helps with the formation of a platelet plug during clotting process. The presence of different mutations in vWF causes a common bleeding disorder named von Willebrand disease.6 The bleeding episodes were usually treated with plasma-derived vWF/factor VIII concentrates which required high doses and long treatment duration. The use of vonicog alfa allows a separate administration of vWF without the presence of the Factor VIII. This separate dosing allows the personalization of the dosage according to the patient's needs.2 On the same note, the plasma-derived vWF concentrates variably lack ULM due to an in vivo exposure to plasma ADAMTS13 and granulocyte elastases. Vonicog alfa can be delivered as an unaltered vWF and it functions as a replacement of vWF. Thus, it mediates platelet adhesion and aggregation as well as stabilization of the procoagulant factor VIII.3

TargetActionsOrganism
ACoagulation factor VIII
stabilization
Humans
ACollagen alpha-1(I) chain
binder
Humans
Absorption

In pharmacokinetic studies, the Cmax, AUC and mean residence time of vonicog alfa are reported to be 90.7 mcg, 1877 h.U/dL and 29.8 hours, respectively.3

Volume of distribution

In phase 3 clinical trials, the volume of distribution of vonicog alfa is reported to be of 0.80 L.3

Protein binding

Vonicog alfa presents a very high plasma protein binding as its main function is performed in the blood.3

Metabolism

The endogenous regulator of the vWF is ADAMTS13. The interaction between these two proteins results in the proteolysis of vWF. This proteolysis occurs primarily in the cleavage site at the domain A2 which is a target domain for ADAMTS13.5

Route of elimination

The majority of vonicog alfa is targeted to the liver and spleen which indicates an active regulatory elimination mechanism. It seems to be uptaken mainly by macrophages.4

Half-life

Clinical trials have shown a terminal half-life of 21.9 hours for vonicog alfa which can be modified by the coadministration of the factor VIII.3

Clearance

In phase 3 clinical trials, the clearance rate of vonicog alfa is reported to be of 0.29 dL/kg/h.3

Adverse Effects
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Toxicity

Studies performed in vitro and in vivo have indicated no mutagenic potential. Carcinogenic or fertility studies have not been performed.8

Affected organisms
  • Humans
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.
Not Available
Food Interactions
Not Available

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VonvendiPowder, for solution650 unitIntravenousShire Pharma Canada UlcNot applicableNot applicableCanada flag
VonvendiPowder, for solution1300 unitIntravenousShire Pharma Canada UlcNot applicableNot applicableCanada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

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

    Learn more
  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

Drug Categories
Not Available
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

Chemical Identifiers

UNII
5PKM8P0G5I
CAS number
109319-16-6

References

General References
  1. Singal M, Kouides PA: Recombinant von Willebrand factor: a first-of-its-kind product for von Willebrand disease. Drugs Today (Barc). 2016 Dec;52(12):653-664. doi: 10.1358/dot.2016.52.12.2570978. [PubMed:28276537]
  2. Brown R: Recombinant von Willebrand factor for severe gastrointestinal bleeding unresponsive to other treatments in a patient with type 2A von Willebrand disease: a case report. Blood Coagul Fibrinolysis. 2017 Oct;28(7):570-575. doi: 10.1097/MBC.0000000000000632. [PubMed:28379876]
  3. Gill JC, Castaman G, Windyga J, Kouides P, Ragni M, Leebeek FW, Obermann-Slupetzky O, Chapman M, Fritsch S, Pavlova BG, Presch I, Ewenstein B: Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease. Blood. 2015 Oct 22;126(17):2038-46. doi: 10.1182/blood-2015-02-629873. Epub 2015 Aug 3. [PubMed:26239086]
  4. Lenting PJ, Christophe OD, Denis CV: von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends. Blood. 2015 Mar 26;125(13):2019-28. doi: 10.1182/blood-2014-06-528406. Epub 2015 Feb 23. [PubMed:25712991]
  5. Chung MC, Popova TG, Jorgensen SC, Dong L, Chandhoke V, Bailey CL, Popov SG: Degradation of circulating von Willebrand factor and its regulator ADAMTS13 implicates secreted Bacillus anthracis metalloproteases in anthrax consumptive coagulopathy. J Biol Chem. 2008 Apr 11;283(15):9531-42. doi: 10.1074/jbc.M705871200. Epub 2008 Feb 8. [PubMed:18263586]
  6. Boston Children's Hospital [Link]
  7. EMA [Link]
  8. FDA application [Link]
  9. National Institute for Health Research [Link]
  10. Hemophilia [Link]
PubChem Substance
347911400
RxNav
1812589
FDA label
Download (1.51 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedPreventionVon Willebrand's Disease1
3CompletedTreatmentVon Willebrand's Disease1
3RecruitingPreventionVon Willebrand's Disease1
3RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19) / Von Willebrand's Disease1
3RecruitingTreatmentVon Willebrand Diseases1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous130 UI
Injection, powder, for solutionIntravenous650 UI
Powder, for solutionIntravenous1300 unit
Powder, for solutionIntravenous650 unit
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Stabilization
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. Brown R: Recombinant von Willebrand factor for severe gastrointestinal bleeding unresponsive to other treatments in a patient with type 2A von Willebrand disease: a case report. Blood Coagul Fibrinolysis. 2017 Oct;28(7):570-575. doi: 10.1097/MBC.0000000000000632. [PubMed:28379876]
  2. Gill JC, Castaman G, Windyga J, Kouides P, Ragni M, Leebeek FW, Obermann-Slupetzky O, Chapman M, Fritsch S, Pavlova BG, Presch I, Ewenstein B: Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease. Blood. 2015 Oct 22;126(17):2038-46. doi: 10.1182/blood-2015-02-629873. Epub 2015 Aug 3. [PubMed:26239086]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Platelet-derived growth factor binding
Specific Function
Type I collagen is a member of group I collagen (fibrillar forming collagen).
Gene Name
COL1A1
Uniprot ID
P02452
Uniprot Name
Collagen alpha-1(I) chain
Molecular Weight
138941.105 Da
References
  1. Brown R: Recombinant von Willebrand factor for severe gastrointestinal bleeding unresponsive to other treatments in a patient with type 2A von Willebrand disease: a case report. Blood Coagul Fibrinolysis. 2017 Oct;28(7):570-575. doi: 10.1097/MBC.0000000000000632. [PubMed:28379876]
  2. Gill JC, Castaman G, Windyga J, Kouides P, Ragni M, Leebeek FW, Obermann-Slupetzky O, Chapman M, Fritsch S, Pavlova BG, Presch I, Ewenstein B: Hemostatic efficacy, safety, and pharmacokinetics of a recombinant von Willebrand factor in severe von Willebrand disease. Blood. 2015 Oct 22;126(17):2038-46. doi: 10.1182/blood-2015-02-629873. Epub 2015 Aug 3. [PubMed:26239086]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.
Specific Function
Calcium ion binding
Gene Name
ADAMTS13
Uniprot ID
Q76LX8
Uniprot Name
A disintegrin and metalloproteinase with thrombospondin motifs 13
Molecular Weight
153603.05 Da
References
  1. Chung MC, Popova TG, Jorgensen SC, Dong L, Chandhoke V, Bailey CL, Popov SG: Degradation of circulating von Willebrand factor and its regulator ADAMTS13 implicates secreted Bacillus anthracis metalloproteases in anthrax consumptive coagulopathy. J Biol Chem. 2008 Apr 11;283(15):9531-42. doi: 10.1074/jbc.M705871200. Epub 2008 Feb 8. [PubMed:18263586]

Drug created on October 20, 2016 18:56 / Updated on June 12, 2020 11:42