Details of the Drug

General Information of Drug (ID: DM0AQ83)

Drug Name
Emicizumab
Indication
Disease Entry ICD 11 Status REF
Factor VIII deficiency 3B10 Approved [1]
Drug Type
Antibody
Sequence
>heavy chain 1
QVQLVESGGGLVQPGGSLRLSCAASGFTFSYYDIQWVRQAPGKGLEWVSSISPSGQSTYY
RREVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRTGREYGGGWYFDYWGQGTLVT
VSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLSSVVTVPSSSLGTQTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQKE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW
QEGNVFSCSVMHEALHNRYTQKSLSLSP
>heavy chain 2
QVQLVQSGSELKKPGASVKVSCKASGYTFTDNNMDWVRQAPGQGLEWMGDINTRSGGSIY
NEEFQDRVIMTVDKSTDTAYMELSSLRSEDTATYHCARRKSYGYYLDEWGEGTLVTVSSA
STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN
QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQEGN
VFSCSVMHEALHNHYTQESLSLSP
>light chain
DIQMTQSPSSLSASVGDRVTITCKASRNIERQLAWYQQKPGQAPELLIYQASRKESGVPD
RFSGSRYGTDFTLTISSLQPEDIATYYCQQYSDPPLTFGGGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 304 mgday/L [2]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 5.92 mg/L [2]
Bioavailability
The bioavailability of drug is 80.4-93.1% [2]
Clearance
The clearance of drug is 0.24 L/day [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 27.8 - 34.4 days [3]
Metabolism
The drug is metabolized via recycling [4]
Vd
The volume of distribution (Vd) of drug is 11.4 L [2]
Cross-matching ID
DrugBank ID
DB13923
TTD ID
D09XTN

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Coagulation factor IX (F9) TTFEZ5Q FA9_HUMAN Modulator [1]
Coagulation factor Xa (F10) TTCIHJA FA10_HUMAN Modulator [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Factor VIII deficiency
ICD Disease Classification 3B10
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Coagulation factor Xa (F10) DTT F10 4.84E-02 -0.28 -0.9
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
2 Yoneyama K, Schmitt C, Kotani N, Levy GG, Kasai R, Iida S, Shima M, Kawanishi T: A Pharmacometric Approach to Substitute for a Conventional Dose-Finding Study in Rare Diseases: Example of Phase III Dose Selection for Emicizumab in Hemophilia A. Clin Pharmacokinet. 2018 Sep;57(9):1123-1134. doi: 10.1007/s40262-017-0616-3.
3 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4 Li K, Xu Y: Citrate metabolism in blood transfusions and its relationship due to metabolic alkalosis and respiratory acidosis. Int J Clin Exp Med. 2015 Apr 15;8(4):6578-84. eCollection 2015.
5 BAX326 (RIXUBIS): a novel recombinant factor IX for the control and prevention of bleeding episodes in adults and children with hemophilia B. Ther Adv Hematol. 2014 Oct;5(5):168-80.
6 Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. Blood. 2012 September 20; 120(12): 2405-2411.
7 Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation. J Thromb Haemost. 2014 Feb;12(2):206-13.
8 Clinical pipeline report, company report or official report of uniQure.
9 Factor IX assay discrepancies in the setting of liver gene therapy using a hyperfunctional variant factor IX-Padua. J Thromb Haemost. 2021 May;19(5):1212-1218.
10 Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study. J Thromb Haemost. 2008 Mar;6(3):457-63.
11 Phase I/II clinical trial of AMT-060 for treating hemophilia B. uniQure N.V.
12 ClinicalTrials.gov (NCT02695160) Ascending Dose Study of Genome Editing by Zinc Finger Nuclease Therapeutic SB-FIX in Subjects With Severe Hemophilia B. U.S. National Institutes of Health.
13 Assessing the potential for AAV vector genotoxicity in a murine model. Correction in: Blood. 2011 June 16; 117(24): 6739.
14 Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B. Blood. 2011 Sep 8;118(10):2695-701.
15 Pfizer. Product Development Pipeline. March 31 2009.
16 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
17 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2359).
18 Company report (Portola)
19 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
20 Serum zinc concentrations: contamination from laboratory equipment. JPEN J Parenter Enteral Nutr. 1979 May-Jun;3(3):179-81.
21 Biochemistry and clinical pharmacology of new anticoagulant agents. Pathophysiol Haemost Thromb. 2002 Sep-Dec;32(5-6):218-24.
22 Effect of factor X inhibition on coagulation activation and cytokine induction in human systemic inflammation. J Infect Dis. 2002 Nov 1;186(9):1270-6.
23 Haemophilia B: Christmas disease. Expert Opin Pharmacother. 2005 Aug;6(9):1517-24.