Efanesoctocog alfa; Recombinant DNA-derived, Factor VIII; F8

Specification

• Cat#: THP-1104
• Product Name: Efanesoctocog alfa; Recombinant DNA-derived, Factor VIII; F8
• Description: Efanesoctocog alfa is a recombinant DNA-derived, Factor VIII concentrate indicated for routine prophylaxis, on-demand treatment and control of bleeding episodes, and perioperative management of bleeding in patients with hemophilia A.
• Sequences: >BddFVIII-Fc chain ATRRYYLGAVELSWDYMQSDLGELPVDARFPPRVPKSFPFNTSVVYKKTLFVEFTDHLFNIAKPRPPWMGLLGPTIQAEVYDTVVITLKNMASHPVSLHAVGVSYWKASEGAEYDDQTSQREKEDDKVFPGGSHTYVWQVLKENGPMASDPLCLTYSYLSHVDLVKDLNSGLIGALLVCREGSLAKEKTQTLHKFILLFAVFDEGKSWHSETKNSLMQDRDAASARAWPKMHTVNGYVNRSLPGLIGCHRKSVYWHVIGMGTTPEVHSIFLEGHTFLVRNHRQASLEISPITFLTAQTLLMDLGQFLLFCHISSHQHDGMEAYVKVDSCPEEPQLRMKNNEEAEDYDDDLTDSEMDVVRFDDDNSPSFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLAPDDRSYKSQYLNNGPQRIGRKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTLLIIFKNQASRPYNIYPHGITDVRPLYSRRLPKGVKHLKDFPILPGEIFKYKWTVTVEDGPTKSDPRCLTRYYSSFVNMERDLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDENRSWYLTENIQRFLPNPAGVQLEDPEFQASNIMHSINGYVFDSLQLSVCLHEVAYWYILSIGAQTDFLSVFFSGYTFKHKMVYEDTLTLFPFSGETVFMSMENPGLWILGCHNSDFRNRGMTALLKVSSCDKNTGDYYEDSYEDISAYLLSKNNAIEPRSFSQNGTSESATPESGPGSEPATSGSETPGTSESATPESGPGSEPATSGSETPGTSESATPESGPGTSTEPSEGSAPGSPAGSPTSTEEGTSESATPESGPGSEPATSGSETPGTSESATPESGPGSPAGSPTSTEEGSPAGSPTSTEEGTSTEPSEGSAPGTSESATPESGPGTSESATPESGPGTSESATPESGPGSEPATSGSETPGSEPATSGSETPGSPAGSPTSTEEGTSTEPSEGSAPGTSTEPSEGSAPGSEPATSGSETPGTSESATPESGPGTSTEPSEGSAPASSEITRTTLQSDQEEIDYDDTISVEMKKEDFDIYDEDENQSPRSFQKKTRHYFIAAVERLWDYGMSSSPHVLRNRAQSGSVPQFKKVVFQEFTDGSFTQPLYRGELNEHLGLLGPYIRAEVEDNIMVTFRNQASRPYSFYSSLISYEEDQRQGAEPRKNFVKPNETKTYFWKVQHHMAPTKDEFDCKAWAYFSDVDLEKDVHSGLIGPLLVCHTNTLNPAHGRQVTVQEFALFFTIFDETKSWYFTENMERNCRAPCNIQMEDPTFKENYRFHAINGYIMDTLPGLVMAQDQRIRWYLLSMGSNENIHSIHFSGHVFTVRKKEEYKMALYNLYPGVFETVEMLPSKAGIWRVECLIGEHLHAGMSTLFLVYSNKCQTPLGMASGHIRDFQITASGQYGQWAPKLARLHYSGSINAWSTKEPFSWIKVDLLAPMIIHGIKTQGARQKFSSLYISQFIIMYSLDGKKWQTYRGNSTGTLMVFFGNVDSSGIKHNIFNPPIIARYIRLHPTHYSIRSTLRMELMGCDLNSCSMPLGMESKAISDAQITASSYFTNMFATWSPSKARLHLQGRSNAWRPQVNNPKEWLQVDFQKTMKVTGVTTQGVKSLLTSMYVKEFLISSSQDGHQWTLFFQNGKVKVFQGNQDSFTPVVNSLDPPLLTRYLRIHPQSWVHQIALRMEVLGCEAQDLYDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >vWF fragment-FVIII a2-Fc chain SLSCRPPMVKLVCPADNLRAEGLECTKTCQNYDLECMSMGCVSGCLCPPGMVRHENRCVALERCPCFHQGKEYAPGETVKIGCNTCVCRDRKWNCTDHVCDATCSTIGMAHYLTFDGLKYLFPGECQYVLVQDYCGSNPGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNVKRPMKDETHFEVVESGRYIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQNNDLTSSNLQVEEDPVDFGNSWKVSSQCADTRKVPLDSSPATCHNNIMKQTMVDSSCRILTSDVFQDCNKLVDPEPYLDVCIYDTCSCESIGDCAAFCDTIAAYAHVCAQHGKVVTWRTATLCPQSCEERNLRENGYEAEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKILDELLQTCVDPEDCPVCEVAGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEPGTSESATPESGPGSEPATSGSETPGTSESATPESGPGSEPATSGSETPGTSESATPESGPGTSTEPSEGSAPGSPAGSPTSTEEGTSESATPESGPGSEPATSGSETPGTSESATPESGPGSPAGSPTSTEEGSPAGSPTSTEEGASSDKNTGDYYEDSYEDISAYLLSKNNAIEPRSFSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
• Species: Human
• Molecular Weight: 312000.0 Da (approximate)
• Introduction: Efanesoctocog alfa is a recombinant factor VIII (FVIII) analogue fusion protein used for the routine prophylaxis, perioperative management of bleeding and on-demand treatment and control of bleeding episodes in patients with hemophilia A. The use of FVIII replacement products is beneficial in patients with hemophilia A; however, their quality of life can be affected due to frequent doses. Efanesoctocog alfa was designed to have an extended half-life, and to surpass the half-life ceiling to which other forms of recombinant FVIII are subjected due to their association with von Willebrand factor (VWF). Endogenous VWF protects FVIII from degradation but also sets a half-life of approximately 15 to 19 h. To extend the half-life of FVIII, efanesoctocog alfa is fused to dimeric Fc, a D'D3 domain of VWF, and two XTEN polypeptides. In February 2023, efanesoctocog alfa was approved by the FDA as a new class of factor VIII therapy for hemophilia A.
• Cas No: 2252477-42-0
• Biologic Classification: Protein Based Therapies Blood factors / Fusion proteins
• Physical Appearance: Solid

Pharmaceutical Information

• Pharmacodynamics: The efficacy of efanesoctocog alfa is comparable to that of recombinant factor VIII (FVIII). Both promote fibrin clot formation and injury‐induced platelet accumulation and have a similar hemostatic potential. The use of 50 IU/kg of efanesoctocog alfa once a week resulted in FVIII levels associated with a low risk of bleeding. Efanesoctocog alfa has an acceptable side-effect profile and is usually well tolerated. However, patients treated with efanesoctocog alfa may present allergic-type hypersensitivity reactions, including anaphylaxis. Also, the formation of FVIII neutralizing antibodies is possible following the administration of efanesoctocog alfa.
• Mechanism of action: Efanesoctocog alfa is a recombinant factor VIII (FVIII) analogue fusion protein that temporarily replaces the missing coagulation FVIII needed for effective hemostasis.6 It is formed by a single recombinant FVIII protein fused to dimeric Fc, a D'D3 domain of von Willebrand factor (VWF), and two XTEN polypeptides, and was designed to have an extended half-life. In plasma, most FVIII circulates in a complex with VWF, which protects FVIII from degradation and extends its half-life. However, it also sets a half-life ceiling of approximately 15 to 19 h. Linking the D'D3 domain of VWF to the recombinant FVIII-Fc fusion protein provides protection and stability to FVIII and prevents FVIII interaction with endogenous VWF. The lysosomal degradation of efanesoctocog alfa is delayed thanks to the Fc region of human immunoglobulin G1 (IgG1) that binds to the neonatal Fc receptor (FcRn), and the XTEN polypeptides alter the hydrodynamic radius of the fusion protein and reduce clearance and degradation rates. Altogether, these modifications lead to a 3- to 4-fold increase in FVIII half-life. Hemophilia A is a genetic disorder caused by missing or defective FVIII. The use of efanesoctocog alfa in patients with hemophilia A increases FVIII plasma levels, temporarily correcting coagulation deficiency.
• Affected organisms: Humans and other mammals
• Targets: 1. Coagulation factor IX; 2. Coagulation factor X; 3. Low-density lipoprotein receptor-related protein 2; 4. Basement membrane-specific heparan sulfate proteoglycan core protein