Detailed description page of ThPDB2
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Th1787 details |
| Primary information | |
|---|---|
| ID | 16274 |
| Therapeutic ID | Th1787 |
| Protein Name | Vonicog alfa |
| Sequence | >Th1787_Vonicog_alfa MIPARFAGVLLALALILPGTLCAEGTRGRSSTARCSLFGSDFVNTFDGSMYSFAGYCSYLAGGCQKRSFSIIGDFQNGKRVSLSVYLGEFFDIHLFVNGTVTQGDQRVSMPYASKGLYLETEAGYYKLSGEAYGFVARIDGSGNFQVLLSDRYFNKTCGLCGNFNIFAEDDFMTQEGTLTSDPYDFANSWALSSGEQWCERASPPSSSCNISSGEMQKGLWEQCQLLKSTSVFARCHPLVDPEPFVALCEKTLCECAGGLECACPALLEYARTCAQEGMVLYGWTDHSACSPVCPAGMEYRQCVSPCARTCQSLHINEMCQERCVDGCSCPEGQLLDEGLCVESTECPCVHSGKRYPPGTSLSRDCNTCICRNSQWICSNEECPGECLVTGQSHFKSFDNRYFTFSGICQYLLARDCQDHSFSIVIETVQCADDRDAVCTRSVTVRLPGLHNSLVKLKHGAGVAMDGQDIQLPLLKGDLRIQHTVTASVRLSYGEDLQMDWDGRGRLLVKLSPVYAGKTCGLCGNYNGNQGDDFLTPSGLAEPRVEDFGNAWKLHGDCQDLQKQHSDPCALNPRMTRFSEEACAVLTSPTFEACHRAVSPLPYLRNCRYDVCSCSDGRECLCGALASYAAACAGRGVRVAWREPGRCELNCPKGQVYLQCGTPCNLTCRSLSYPDEECNEACLEGCFCPPGLYMDERGDCVPKAQCPCYYDGEIFQPEDIFSDHHTMCYCEDGFMHCTMSGVPGSLLPDAVLSSPLSHRSKRSLSCRPPMVKLVCPADNLRAEGLECTKTCQNYDLECMSMGCVSGCLCPPGMVRHENRCVALERCPCFHQGKEYAPGETVKIGCNTCVCRDRKWNCTDHVCDATCSTIGMAHYLTFDGLKYLFPGECQYVLVQDYCGSNPGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNVKRPMKDETHFEVVESGRYIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVEEDPVDFGNSWKVSSQCADTRKVPLDSSPATCHNNIMKQTMVDSSCRILTSDVFQDCNKLVDPEPYLDVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTATLCPQSCEERNLRENGYECEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKILDELLQTCVDPEDCPVCEVAGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEPGGLVVPPTDAPVSPTTLYVEDISEPPLHDFYCSRLLDLVFLLDGSSRLSEAEFEVLKAFVVDMMERLRISQKWVRVAVVEYHDGSHAYIGLKDRKRPSELRRIASQVKYAGSQVASTSEVLKYTLFQIFSKIDRPEASRIALLLMASQEPQRMSRNFVRYVQGLKKKKVIVIPVGIGPHANLKQIRLIEKQAPENKAFVLSSVDELEQQRDEIVSYLCDLAPEAPPPTLPPHMAQVTVGPGLLGVSTLGPKRNSMVLDVAFVLEGSDKIGEADFNRSKEFMEEVIQRMDVGQDSIHVTVLQYSYMVTVEYPFSEAQSKGDILQRVREIRYQGGNRTNTGLALRYLSDHSFLVSQGDREQAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPNANVQELERIGWPNAPILIQDFETLPREAPDLVLQRCCSGEGLQIPTLSPAPDCSQPLDVILLLDGSSSFPASYFDEMKSFAKAFISKANIGPRLTQVSVLQYGSITTIDVPWNVVPEKAHLLSLVDVMQREGGPSQIGDALGFAVRYLTSEMHGARPGASKAVVILVTDVSVDSVDAAADAARSNRVTVFPIGIGDRYDAAQLRILAGPAGDSNVVKLQRIEDLPTMVTLGNSFLHKLCSGFVRICMDEDGNEKRPGDVWTLPDQCHTVTCQPDGQTLLKSHRVNCDRGLRPSCPNSQSPVKVEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVLFQNKEQDLEVILHNGACSPGARQGCMKSIEVKHSALSVELHSDMEVTVNGRLVSVPYVGGNMEVNVYGAIMHEVRFNHLGHIFTFTPQNNEFQLQLSPKTFASKTYGLCGICDENGANDFMLRDGTVTTDWKTLVQEWTVQRPGQTCQPILEEQCLVPDSSHCQVLLLPLFAECHKVLAPATFYAICQQDSCHQEQVCEVIASYAHLCRTNGVCVDWRTPDFCAMSCPPSLVYNHCEHGCPRHCDGNVSSCGDHPSEGCFCPPDKVMLEGSCVPEEACTQCIGEDGVQHQFLEAWVPDHQPCQICTCLSGRKVNCTTQPCPTAKAPTCGLCEVARLRQNADQCCPEYECVCDPVSCDLPPVPHCERGLQPTLTNPGECRPNFTCACRKEECKRVSPPSCPPHRLPTLRKTQCCDEYECACNCVNSTVSCPLGYLASTATNDCGCTTTTCLPDKVCVHRSTIYPVGQFWEEGCDVCTCTDMEDAVMGLRVAQCSQKPCEDSCRSGFTYVLHEGECCGRCLPSACEVVTGSPRGDSQSSWKSVGSQWASPENPCLINECVRVKEEVFIQQRNVSCPQLEVPVCPSGFQLSCKTSACCPSCRCERMEACMLNGTVIGPGKTVMIDVCTTCRCMVQVGVISGFKLECRKTTCNPCPLGYKEENNTGECCGRCLPTACTIQLRGGQIMTLKRDETLQDGCDTHFCKVNERGEYFWEKRVTGCPPFDEHKCLAEGGKIMKIPGTCCDTCEEPECNDITARLQYVKVGSCKSEVEVDIHYCQGKCASKAMYSIDINDVQDQCSCCSPTRTEPMQVALHCTNGSVVYHEVLNAMECKCSPRKCSK |
| Molecular Weight | 20000000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| 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.[A32262] |
| Description | Vonicog alfa is a recombinant von Willebrand factor manufactured by Baxalta. It was FDA approved in December 2015.[A32230] The gen of von Willebrand factor was first cloned in 1985 by Stuart Orkin and David Ginsburg.[L1849] By the EMA, vonicog alfa is still under clinical analysis.[L1862] |
| Indication/Disease | Vonicog alfa is indicated for the on-demand treatment and control of bleeding episodes in adults previously diagnosed with von Willebrand disease.[L1866] 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.[L1867] |
| 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.[A32262] |
| 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.[L1849] 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.[A32261] 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.[A32262] |
| Toxicity | Studies performed in vitro and in vivo have indicated no mutagenic potential. Carcinogenic or fertility studies have not been performed.[L1866] |
| 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.[A32290] |
| 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.[A32262] |
| In phase 3 clinical trials, the volume of distribution of vonicog alfa is reported to be of 0.80 L.[A32262] | |
| Clearance | In phase 3 clinical trials, the clearance rate of vonicog alfa is reported to be of 0.29 dL/kg/h.[A32262] |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Coagulation factor VIII,Collagen alpha-1(I) chain |
| Brand Name | Veyvondi |
| Company | Baxalta Innovations Gmb H |
| Brand Description | Baxalta Innovations Gmb H |
| Prescribed For | Intravenous |
| Chemical Name | 650 IU |
| Formulation | NA |
| Physical Appearance | The following side effects may occur during treatment with Veyvondi: hypersensitivity (allergic) reactions, thromboembolic events (problems due to the formation of blood clots in the blood vessels), development of inhibitors (antibodies) against von Willebrand factor, causing the medicine to stop working and resulting in a loss of bleeding control. The most common side effects with Veyvondi (which may affect up to 1 in 10 patients) are dizziness, vertigo (a spinning sensation), dysgeusia (taste disturbances), tremor, rapid heartbeat, deep venous thrombosis (blood clot in a deep vein, usually in the leg), hypertension (high blood pressure), hot flush, vomiting, nausea (feeling sick), pruritus (itching), chest discomfort, sensations like numbness, tingling, pins and n |
| Route of Administration | Veyvondi is available as a powder and solvent that are mixed together to make a solution for injection into a vein. The dose and frequency of treatment depend on the type and seriousness of the bleeding episode or extent of the surgery, and the patient’s condition and body weight. |
| Recommended Dosage | to treat bleeding episodes |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 16275 |
| Therapeutic ID | Th1787 |
| Protein Name | Vonicog alfa |
| Sequence | >Th1787_Vonicog_alfa MIPARFAGVLLALALILPGTLCAEGTRGRSSTARCSLFGSDFVNTFDGSMYSFAGYCSYLAGGCQKRSFSIIGDFQNGKRVSLSVYLGEFFDIHLFVNGTVTQGDQRVSMPYASKGLYLETEAGYYKLSGEAYGFVARIDGSGNFQVLLSDRYFNKTCGLCGNFNIFAEDDFMTQEGTLTSDPYDFANSWALSSGEQWCERASPPSSSCNISSGEMQKGLWEQCQLLKSTSVFARCHPLVDPEPFVALCEKTLCECAGGLECACPALLEYARTCAQEGMVLYGWTDHSACSPVCPAGMEYRQCVSPCARTCQSLHINEMCQERCVDGCSCPEGQLLDEGLCVESTECPCVHSGKRYPPGTSLSRDCNTCICRNSQWICSNEECPGECLVTGQSHFKSFDNRYFTFSGICQYLLARDCQDHSFSIVIETVQCADDRDAVCTRSVTVRLPGLHNSLVKLKHGAGVAMDGQDIQLPLLKGDLRIQHTVTASVRLSYGEDLQMDWDGRGRLLVKLSPVYAGKTCGLCGNYNGNQGDDFLTPSGLAEPRVEDFGNAWKLHGDCQDLQKQHSDPCALNPRMTRFSEEACAVLTSPTFEACHRAVSPLPYLRNCRYDVCSCSDGRECLCGALASYAAACAGRGVRVAWREPGRCELNCPKGQVYLQCGTPCNLTCRSLSYPDEECNEACLEGCFCPPGLYMDERGDCVPKAQCPCYYDGEIFQPEDIFSDHHTMCYCEDGFMHCTMSGVPGSLLPDAVLSSPLSHRSKRSLSCRPPMVKLVCPADNLRAEGLECTKTCQNYDLECMSMGCVSGCLCPPGMVRHENRCVALERCPCFHQGKEYAPGETVKIGCNTCVCRDRKWNCTDHVCDATCSTIGMAHYLTFDGLKYLFPGECQYVLVQDYCGSNPGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNVKRPMKDETHFEVVESGRYIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVEEDPVDFGNSWKVSSQCADTRKVPLDSSPATCHNNIMKQTMVDSSCRILTSDVFQDCNKLVDPEPYLDVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTATLCPQSCEERNLRENGYECEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKILDELLQTCVDPEDCPVCEVAGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEPGGLVVPPTDAPVSPTTLYVEDISEPPLHDFYCSRLLDLVFLLDGSSRLSEAEFEVLKAFVVDMMERLRISQKWVRVAVVEYHDGSHAYIGLKDRKRPSELRRIASQVKYAGSQVASTSEVLKYTLFQIFSKIDRPEASRIALLLMASQEPQRMSRNFVRYVQGLKKKKVIVIPVGIGPHANLKQIRLIEKQAPENKAFVLSSVDELEQQRDEIVSYLCDLAPEAPPPTLPPHMAQVTVGPGLLGVSTLGPKRNSMVLDVAFVLEGSDKIGEADFNRSKEFMEEVIQRMDVGQDSIHVTVLQYSYMVTVEYPFSEAQSKGDILQRVREIRYQGGNRTNTGLALRYLSDHSFLVSQGDREQAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPNANVQELERIGWPNAPILIQDFETLPREAPDLVLQRCCSGEGLQIPTLSPAPDCSQPLDVILLLDGSSSFPASYFDEMKSFAKAFISKANIGPRLTQVSVLQYGSITTIDVPWNVVPEKAHLLSLVDVMQREGGPSQIGDALGFAVRYLTSEMHGARPGASKAVVILVTDVSVDSVDAAADAARSNRVTVFPIGIGDRYDAAQLRILAGPAGDSNVVKLQRIEDLPTMVTLGNSFLHKLCSGFVRICMDEDGNEKRPGDVWTLPDQCHTVTCQPDGQTLLKSHRVNCDRGLRPSCPNSQSPVKVEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVLFQNKEQDLEVILHNGACSPGARQGCMKSIEVKHSALSVELHSDMEVTVNGRLVSVPYVGGNMEVNVYGAIMHEVRFNHLGHIFTFTPQNNEFQLQLSPKTFASKTYGLCGICDENGANDFMLRDGTVTTDWKTLVQEWTVQRPGQTCQPILEEQCLVPDSSHCQVLLLPLFAECHKVLAPATFYAICQQDSCHQEQVCEVIASYAHLCRTNGVCVDWRTPDFCAMSCPPSLVYNHCEHGCPRHCDGNVSSCGDHPSEGCFCPPDKVMLEGSCVPEEACTQCIGEDGVQHQFLEAWVPDHQPCQICTCLSGRKVNCTTQPCPTAKAPTCGLCEVARLRQNADQCCPEYECVCDPVSCDLPPVPHCERGLQPTLTNPGECRPNFTCACRKEECKRVSPPSCPPHRLPTLRKTQCCDEYECACNCVNSTVSCPLGYLASTATNDCGCTTTTCLPDKVCVHRSTIYPVGQFWEEGCDVCTCTDMEDAVMGLRVAQCSQKPCEDSCRSGFTYVLHEGECCGRCLPSACEVVTGSPRGDSQSSWKSVGSQWASPENPCLINECVRVKEEVFIQQRNVSCPQLEVPVCPSGFQLSCKTSACCPSCRCERMEACMLNGTVIGPGKTVMIDVCTTCRCMVQVGVISGFKLECRKTTCNPCPLGYKEENNTGECCGRCLPTACTIQLRGGQIMTLKRDETLQDGCDTHFCKVNERGEYFWEKRVTGCPPFDEHKCLAEGGKIMKIPGTCCDTCEEPECNDITARLQYVKVGSCKSEVEVDIHYCQGKCASKAMYSIDINDVQDQCSCCSPTRTEPMQVALHCTNGSVVYHEVLNAMECKCSPRKCSK |
| Molecular Weight | 20000000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| 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.[A32262] |
| Description | Vonicog alfa is a recombinant von Willebrand factor manufactured by Baxalta. It was FDA approved in December 2015.[A32230] The gen of von Willebrand factor was first cloned in 1985 by Stuart Orkin and David Ginsburg.[L1849] By the EMA, vonicog alfa is still under clinical analysis.[L1862] |
| Indication/Disease | Vonicog alfa is indicated for the on-demand treatment and control of bleeding episodes in adults previously diagnosed with von Willebrand disease.[L1866] 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.[L1867] |
| 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.[A32262] |
| 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.[L1849] 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.[A32261] 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.[A32262] |
| Toxicity | Studies performed in vitro and in vivo have indicated no mutagenic potential. Carcinogenic or fertility studies have not been performed.[L1866] |
| 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.[A32290] |
| 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.[A32262] |
| In phase 3 clinical trials, the volume of distribution of vonicog alfa is reported to be of 0.80 L.[A32262] | |
| Clearance | In phase 3 clinical trials, the clearance rate of vonicog alfa is reported to be of 0.29 dL/kg/h.[A32262] |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Coagulation factor VIII,Collagen alpha-1(I) chain |
| Brand Name | Veyvondi |
| Company | Baxalta Innovations Gmb H |
| Brand Description | Baxalta Innovations Gmb H |
| Prescribed For | Intravenous |
| Chemical Name | 1300 IU |
| Formulation | NA |
| Physical Appearance | The following side effects may occur during treatment with Veyvondi: hypersensitivity (allergic) reactions, thromboembolic events (problems due to the formation of blood clots in the blood vessels), development of inhibitors (antibodies) against von Willebrand factor, causing the medicine to stop working and resulting in a loss of bleeding control. The most common side effects with Veyvondi (which may affect up to 1 in 10 patients) are dizziness, vertigo (a spinning sensation), dysgeusia (taste disturbances), tremor, rapid heartbeat, deep venous thrombosis (blood clot in a deep vein, usually in the leg), hypertension (high blood pressure), hot flush, vomiting, nausea (feeling sick), pruritus (itching), chest discomfort, sensations like numbness, tingling, pins and n |
| Route of Administration | Veyvondi is available as a powder and solvent that are mixed together to make a solution for injection into a vein. The dose and frequency of treatment depend on the type and seriousness of the bleeding episode or extent of the surgery, and the patient’s condition and body weight. |
| Recommended Dosage | to treat bleeding episodes |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 16276 |
| Therapeutic ID | Th1787 |
| Protein Name | Vonicog alfa |
| Sequence | >Th1787_Vonicog_alfa MIPARFAGVLLALALILPGTLCAEGTRGRSSTARCSLFGSDFVNTFDGSMYSFAGYCSYLAGGCQKRSFSIIGDFQNGKRVSLSVYLGEFFDIHLFVNGTVTQGDQRVSMPYASKGLYLETEAGYYKLSGEAYGFVARIDGSGNFQVLLSDRYFNKTCGLCGNFNIFAEDDFMTQEGTLTSDPYDFANSWALSSGEQWCERASPPSSSCNISSGEMQKGLWEQCQLLKSTSVFARCHPLVDPEPFVALCEKTLCECAGGLECACPALLEYARTCAQEGMVLYGWTDHSACSPVCPAGMEYRQCVSPCARTCQSLHINEMCQERCVDGCSCPEGQLLDEGLCVESTECPCVHSGKRYPPGTSLSRDCNTCICRNSQWICSNEECPGECLVTGQSHFKSFDNRYFTFSGICQYLLARDCQDHSFSIVIETVQCADDRDAVCTRSVTVRLPGLHNSLVKLKHGAGVAMDGQDIQLPLLKGDLRIQHTVTASVRLSYGEDLQMDWDGRGRLLVKLSPVYAGKTCGLCGNYNGNQGDDFLTPSGLAEPRVEDFGNAWKLHGDCQDLQKQHSDPCALNPRMTRFSEEACAVLTSPTFEACHRAVSPLPYLRNCRYDVCSCSDGRECLCGALASYAAACAGRGVRVAWREPGRCELNCPKGQVYLQCGTPCNLTCRSLSYPDEECNEACLEGCFCPPGLYMDERGDCVPKAQCPCYYDGEIFQPEDIFSDHHTMCYCEDGFMHCTMSGVPGSLLPDAVLSSPLSHRSKRSLSCRPPMVKLVCPADNLRAEGLECTKTCQNYDLECMSMGCVSGCLCPPGMVRHENRCVALERCPCFHQGKEYAPGETVKIGCNTCVCRDRKWNCTDHVCDATCSTIGMAHYLTFDGLKYLFPGECQYVLVQDYCGSNPGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNVKRPMKDETHFEVVESGRYIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVEEDPVDFGNSWKVSSQCADTRKVPLDSSPATCHNNIMKQTMVDSSCRILTSDVFQDCNKLVDPEPYLDVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTATLCPQSCEERNLRENGYECEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKILDELLQTCVDPEDCPVCEVAGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEPGGLVVPPTDAPVSPTTLYVEDISEPPLHDFYCSRLLDLVFLLDGSSRLSEAEFEVLKAFVVDMMERLRISQKWVRVAVVEYHDGSHAYIGLKDRKRPSELRRIASQVKYAGSQVASTSEVLKYTLFQIFSKIDRPEASRIALLLMASQEPQRMSRNFVRYVQGLKKKKVIVIPVGIGPHANLKQIRLIEKQAPENKAFVLSSVDELEQQRDEIVSYLCDLAPEAPPPTLPPHMAQVTVGPGLLGVSTLGPKRNSMVLDVAFVLEGSDKIGEADFNRSKEFMEEVIQRMDVGQDSIHVTVLQYSYMVTVEYPFSEAQSKGDILQRVREIRYQGGNRTNTGLALRYLSDHSFLVSQGDREQAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPNANVQELERIGWPNAPILIQDFETLPREAPDLVLQRCCSGEGLQIPTLSPAPDCSQPLDVILLLDGSSSFPASYFDEMKSFAKAFISKANIGPRLTQVSVLQYGSITTIDVPWNVVPEKAHLLSLVDVMQREGGPSQIGDALGFAVRYLTSEMHGARPGASKAVVILVTDVSVDSVDAAADAARSNRVTVFPIGIGDRYDAAQLRILAGPAGDSNVVKLQRIEDLPTMVTLGNSFLHKLCSGFVRICMDEDGNEKRPGDVWTLPDQCHTVTCQPDGQTLLKSHRVNCDRGLRPSCPNSQSPVKVEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVLFQNKEQDLEVILHNGACSPGARQGCMKSIEVKHSALSVELHSDMEVTVNGRLVSVPYVGGNMEVNVYGAIMHEVRFNHLGHIFTFTPQNNEFQLQLSPKTFASKTYGLCGICDENGANDFMLRDGTVTTDWKTLVQEWTVQRPGQTCQPILEEQCLVPDSSHCQVLLLPLFAECHKVLAPATFYAICQQDSCHQEQVCEVIASYAHLCRTNGVCVDWRTPDFCAMSCPPSLVYNHCEHGCPRHCDGNVSSCGDHPSEGCFCPPDKVMLEGSCVPEEACTQCIGEDGVQHQFLEAWVPDHQPCQICTCLSGRKVNCTTQPCPTAKAPTCGLCEVARLRQNADQCCPEYECVCDPVSCDLPPVPHCERGLQPTLTNPGECRPNFTCACRKEECKRVSPPSCPPHRLPTLRKTQCCDEYECACNCVNSTVSCPLGYLASTATNDCGCTTTTCLPDKVCVHRSTIYPVGQFWEEGCDVCTCTDMEDAVMGLRVAQCSQKPCEDSCRSGFTYVLHEGECCGRCLPSACEVVTGSPRGDSQSSWKSVGSQWASPENPCLINECVRVKEEVFIQQRNVSCPQLEVPVCPSGFQLSCKTSACCPSCRCERMEACMLNGTVIGPGKTVMIDVCTTCRCMVQVGVISGFKLECRKTTCNPCPLGYKEENNTGECCGRCLPTACTIQLRGGQIMTLKRDETLQDGCDTHFCKVNERGEYFWEKRVTGCPPFDEHKCLAEGGKIMKIPGTCCDTCEEPECNDITARLQYVKVGSCKSEVEVDIHYCQGKCASKAMYSIDINDVQDQCSCCSPTRTEPMQVALHCTNGSVVYHEVLNAMECKCSPRKCSK |
| Molecular Weight | 20000000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| 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.[A32262] |
| Description | Vonicog alfa is a recombinant von Willebrand factor manufactured by Baxalta. It was FDA approved in December 2015.[A32230] The gen of von Willebrand factor was first cloned in 1985 by Stuart Orkin and David Ginsburg.[L1849] By the EMA, vonicog alfa is still under clinical analysis.[L1862] |
| Indication/Disease | Vonicog alfa is indicated for the on-demand treatment and control of bleeding episodes in adults previously diagnosed with von Willebrand disease.[L1866] 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.[L1867] |
| 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.[A32262] |
| 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.[L1849] 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.[A32261] 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.[A32262] |
| Toxicity | Studies performed in vitro and in vivo have indicated no mutagenic potential. Carcinogenic or fertility studies have not been performed.[L1866] |
| 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.[A32290] |
| 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.[A32262] |
| In phase 3 clinical trials, the volume of distribution of vonicog alfa is reported to be of 0.80 L.[A32262] | |
| Clearance | In phase 3 clinical trials, the clearance rate of vonicog alfa is reported to be of 0.29 dL/kg/h.[A32262] |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Coagulation factor VIII,Collagen alpha-1(I) chain |
| Brand Name | Vonvendi |
| Company | Takeda |
| Brand Description | Takeda |
| Prescribed For | Intravenous |
| Chemical Name | 650 unit / vial |
| Formulation | VONVENDI is contraindicated in patients who have had life-threatening hypersensitivity reactions to VONVENDI or constituents of the product (tri-sodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate, polysorbate 80, and hamster or mouse proteins). [see DESCRIPTION] |
| Physical Appearance | generalized itching, rapid heart rate, nausea, tingling or pricking sensation at the infusion site, chest discomfort, hot flashes, flushing, high blood pressure (hypertension), dizziness, changes in taste, and tremor |
| Route of Administration | Vonvendi is a naturally occurring protein in the blood that helps blood to clot. People with an inherited blood-clotting disorder called von Willebrand disease do not have enough of this protein in their blood. A lack of von Willebrand factor can cause uncontrolled bleeding. Vonvendi is used in adults... |
| Recommended Dosage | VONVENDI [von Willebrand factor (recombinant)] is a recombinant von Willebrand factor (rVWF) indicated for use in adults (age 18 and older) diagnosed with von Willebrand disease (VWD) for: |
| Contraindication | NA |
| Side Effects | Stockschlaeder M, Schneppenheim R, Budde U, Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis. Blood Coagul Fibrinolysis 2014, 25:206-216. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 16277 |
| Therapeutic ID | Th1787 |
| Protein Name | Vonicog alfa |
| Sequence | >Th1787_Vonicog_alfa MIPARFAGVLLALALILPGTLCAEGTRGRSSTARCSLFGSDFVNTFDGSMYSFAGYCSYLAGGCQKRSFSIIGDFQNGKRVSLSVYLGEFFDIHLFVNGTVTQGDQRVSMPYASKGLYLETEAGYYKLSGEAYGFVARIDGSGNFQVLLSDRYFNKTCGLCGNFNIFAEDDFMTQEGTLTSDPYDFANSWALSSGEQWCERASPPSSSCNISSGEMQKGLWEQCQLLKSTSVFARCHPLVDPEPFVALCEKTLCECAGGLECACPALLEYARTCAQEGMVLYGWTDHSACSPVCPAGMEYRQCVSPCARTCQSLHINEMCQERCVDGCSCPEGQLLDEGLCVESTECPCVHSGKRYPPGTSLSRDCNTCICRNSQWICSNEECPGECLVTGQSHFKSFDNRYFTFSGICQYLLARDCQDHSFSIVIETVQCADDRDAVCTRSVTVRLPGLHNSLVKLKHGAGVAMDGQDIQLPLLKGDLRIQHTVTASVRLSYGEDLQMDWDGRGRLLVKLSPVYAGKTCGLCGNYNGNQGDDFLTPSGLAEPRVEDFGNAWKLHGDCQDLQKQHSDPCALNPRMTRFSEEACAVLTSPTFEACHRAVSPLPYLRNCRYDVCSCSDGRECLCGALASYAAACAGRGVRVAWREPGRCELNCPKGQVYLQCGTPCNLTCRSLSYPDEECNEACLEGCFCPPGLYMDERGDCVPKAQCPCYYDGEIFQPEDIFSDHHTMCYCEDGFMHCTMSGVPGSLLPDAVLSSPLSHRSKRSLSCRPPMVKLVCPADNLRAEGLECTKTCQNYDLECMSMGCVSGCLCPPGMVRHENRCVALERCPCFHQGKEYAPGETVKIGCNTCVCRDRKWNCTDHVCDATCSTIGMAHYLTFDGLKYLFPGECQYVLVQDYCGSNPGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNVKRPMKDETHFEVVESGRYIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVEEDPVDFGNSWKVSSQCADTRKVPLDSSPATCHNNIMKQTMVDSSCRILTSDVFQDCNKLVDPEPYLDVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTATLCPQSCEERNLRENGYECEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKILDELLQTCVDPEDCPVCEVAGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEPGGLVVPPTDAPVSPTTLYVEDISEPPLHDFYCSRLLDLVFLLDGSSRLSEAEFEVLKAFVVDMMERLRISQKWVRVAVVEYHDGSHAYIGLKDRKRPSELRRIASQVKYAGSQVASTSEVLKYTLFQIFSKIDRPEASRIALLLMASQEPQRMSRNFVRYVQGLKKKKVIVIPVGIGPHANLKQIRLIEKQAPENKAFVLSSVDELEQQRDEIVSYLCDLAPEAPPPTLPPHMAQVTVGPGLLGVSTLGPKRNSMVLDVAFVLEGSDKIGEADFNRSKEFMEEVIQRMDVGQDSIHVTVLQYSYMVTVEYPFSEAQSKGDILQRVREIRYQGGNRTNTGLALRYLSDHSFLVSQGDREQAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPNANVQELERIGWPNAPILIQDFETLPREAPDLVLQRCCSGEGLQIPTLSPAPDCSQPLDVILLLDGSSSFPASYFDEMKSFAKAFISKANIGPRLTQVSVLQYGSITTIDVPWNVVPEKAHLLSLVDVMQREGGPSQIGDALGFAVRYLTSEMHGARPGASKAVVILVTDVSVDSVDAAADAARSNRVTVFPIGIGDRYDAAQLRILAGPAGDSNVVKLQRIEDLPTMVTLGNSFLHKLCSGFVRICMDEDGNEKRPGDVWTLPDQCHTVTCQPDGQTLLKSHRVNCDRGLRPSCPNSQSPVKVEETCGCRWTCPCVCTGSSTRHIVTFDGQNFKLTGSCSYVLFQNKEQDLEVILHNGACSPGARQGCMKSIEVKHSALSVELHSDMEVTVNGRLVSVPYVGGNMEVNVYGAIMHEVRFNHLGHIFTFTPQNNEFQLQLSPKTFASKTYGLCGICDENGANDFMLRDGTVTTDWKTLVQEWTVQRPGQTCQPILEEQCLVPDSSHCQVLLLPLFAECHKVLAPATFYAICQQDSCHQEQVCEVIASYAHLCRTNGVCVDWRTPDFCAMSCPPSLVYNHCEHGCPRHCDGNVSSCGDHPSEGCFCPPDKVMLEGSCVPEEACTQCIGEDGVQHQFLEAWVPDHQPCQICTCLSGRKVNCTTQPCPTAKAPTCGLCEVARLRQNADQCCPEYECVCDPVSCDLPPVPHCERGLQPTLTNPGECRPNFTCACRKEECKRVSPPSCPPHRLPTLRKTQCCDEYECACNCVNSTVSCPLGYLASTATNDCGCTTTTCLPDKVCVHRSTIYPVGQFWEEGCDVCTCTDMEDAVMGLRVAQCSQKPCEDSCRSGFTYVLHEGECCGRCLPSACEVVTGSPRGDSQSSWKSVGSQWASPENPCLINECVRVKEEVFIQQRNVSCPQLEVPVCPSGFQLSCKTSACCPSCRCERMEACMLNGTVIGPGKTVMIDVCTTCRCMVQVGVISGFKLECRKTTCNPCPLGYKEENNTGECCGRCLPTACTIQLRGGQIMTLKRDETLQDGCDTHFCKVNERGEYFWEKRVTGCPPFDEHKCLAEGGKIMKIPGTCCDTCEEPECNDITARLQYVKVGSCKSEVEVDIHYCQGKCASKAMYSIDINDVQDQCSCCSPTRTEPMQVALHCTNGSVVYHEVLNAMECKCSPRKCSK |
| Molecular Weight | 20000000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| 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.[A32262] |
| Description | Vonicog alfa is a recombinant von Willebrand factor manufactured by Baxalta. It was FDA approved in December 2015.[A32230] The gen of von Willebrand factor was first cloned in 1985 by Stuart Orkin and David Ginsburg.[L1849] By the EMA, vonicog alfa is still under clinical analysis.[L1862] |
| Indication/Disease | Vonicog alfa is indicated for the on-demand treatment and control of bleeding episodes in adults previously diagnosed with von Willebrand disease.[L1866] 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.[L1867] |
| 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.[A32262] |
| 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.[L1849] 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.[A32261] 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.[A32262] |
| Toxicity | Studies performed in vitro and in vivo have indicated no mutagenic potential. Carcinogenic or fertility studies have not been performed.[L1866] |
| 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.[A32290] |
| 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.[A32262] |
| In phase 3 clinical trials, the volume of distribution of vonicog alfa is reported to be of 0.80 L.[A32262] | |
| Clearance | In phase 3 clinical trials, the clearance rate of vonicog alfa is reported to be of 0.29 dL/kg/h.[A32262] |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Coagulation factor VIII,Collagen alpha-1(I) chain |
| Brand Name | Vonvendi |
| Company | Takeda |
| Brand Description | Takeda |
| Prescribed For | Intravenous |
| Chemical Name | 1300 unit / vial |
| Formulation | VONVENDI is contraindicated in patients who have had life-threatening hypersensitivity reactions to VONVENDI or constituents of the product (tri-sodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate, polysorbate 80, and hamster or mouse proteins). [see DESCRIPTION] |
| Physical Appearance | generalized itching, rapid heart rate, nausea, tingling or pricking sensation at the infusion site, chest discomfort, hot flashes, flushing, high blood pressure (hypertension), dizziness, changes in taste, and tremor |
| Route of Administration | Vonvendi is a naturally occurring protein in the blood that helps blood to clot. People with an inherited blood-clotting disorder called von Willebrand disease do not have enough of this protein in their blood. A lack of von Willebrand factor can cause uncontrolled bleeding. Vonvendi is used in adults... |
| Recommended Dosage | VONVENDI [von Willebrand factor (recombinant)] is a recombinant von Willebrand factor (rVWF) indicated for use in adults (age 18 and older) diagnosed with von Willebrand disease (VWD) for: |
| Contraindication | NA |
| Side Effects | Stockschlaeder M, Schneppenheim R, Budde U, Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis. Blood Coagul Fibrinolysis 2014, 25:206-216. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |