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Identification
- Summary
Emicizumab is an antibody against Factor IXa and Factor X used to treat hemophilia A.
- Brand Names
- Hemlibra
- Generic Name
- Emicizumab
- DrugBank Accession Number
- DB13923
- Background
Emicizumab is a humanized recombinant monoclonal antibody that mimics the function of the coagulation Factor VIII and it has the capacity to bind simultaneously to activated Factor IX and Factor X. The ability of Emicizumab to bind to all these three different factors allows it to overcome immunogenicity and unstable hemostatic efficacy produced by previous Factor VII agents. Emicizumab was originated as an improved form of hBS23 and it was approved on November 16, 2017.1,8 It was created by Chugai Pharmaceuticals Co. Ltd. and co-developed with Roche and Genentech.7
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6434-H9940-N1724-O2047-S45
- Protein Average Weight
- 145637.0 Da
- Sequences
>>>Emicizumab heavy chain 1<<<< QVQLVESGGGLVQPGGSLRLSCAASGFTFSYYDIQWVRQAPGKGLEWVSSISPSGQSTYY RREVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRTGREYGGGWYFDYWGQGTLVT VSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQKE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QEGNVFSCSVMHEALHNRYTQKSLSLSP
>>>Emicizumab heavy chain 2<<<< QVQLVQSGSELKKPGASVKVSCKASGYTFTDNNMDWVRQAPGQGLEWMGDINTRSGGSIY NEEFQDRVIMTVDKSTDTAYMELSSLRSEDTATYHCARRKSYGYYLDEWGEGTLVTVSSA STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTQTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQEGN VFSCSVMHEALHNHYTQESLSLSP
>>>Emicizumab light chain<<<< DIQMTQSPSSLSASVGDRVTITCKASRNIERQLAWYQQKPGQAPELLIYQASRKESGVPD RFSGSRYGTDFTLTISSLQPEDIATYYCQQYSDPPLTFGGGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- KEGG [Link]
- Synonyms
- Emicizumab
- emicizumab-kxwh
- External IDs
- ACE 910
- ACE-910
- ACE910
Pharmacology
- Indication
The main function of Emicizumab is the prevention of bleeding episodes. Thus, Emicizumab is approved for the routine prophylaxis to prevent or reduce the frequency of bleeding episodes of adult and pediatric patients with hemophilia A with or without Factor VIII inhibitors.11
Hemophilia A is a deficiency of coagulation Factor VIII which causes a serious bleeding disorder. The standard treatment is done with the administration of recombinant or serum-deriver Factor VIII which induces the formation of anti-factor VIII alloantibodies (Factor VIII inhibitors) and renders the standard treatment ineffective.2
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in prophylaxis of Bleeding caused by hemophilia a •••••••••••• Prophylaxis of Bleeding caused by hemophilia a •••••••••••• - Contraindications & Blackbox Warnings
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Emicizumab mimics the function of coagulation factor VIII, therefore it binds to the activated form of Factor IX (Factor IXa). This binding forms a complex that will later bind to the X factor of the coagulation factor. 4 The ability of Emicizumab to interact with both factors (Factor IXa and Factor X) activates the coagulation cascade that will subsequently lead to the segmentation of fibrinogen into fibrin and the formation of blood clots.3 The effect of Emicizumab is translated into the restoration of the blood coagulation process and, therefore, in the reduction of hemorrhagic episodes.8 The activity of emicizumab can also produce changes in activated clotting time (ACT), activated partial thromboplastin time (aPTT) and one-step Factor VIII activity. 10 In addition, the unique bispecific structure of Emicizumab prevents the formation of Factor VIII inhibitors or their effect. 2
In the first clinical trials, emicizumab was tried on previously treated adult and pediatric patients of hemophilia A with FVIII inhibitors. In this trials, the annualized bleeding rate requiring treatment with coagulation factors was reduced by 87% when compared to untreated patients.12
Those clinical trials were followed by a second round on previously treated patients of severe hemophilia A without FVIII inhibitors. In this trial, the annualized bleed rate was reduced by 96% when compared to untreated patients.12
- Mechanism of action
Emicizumab exerts its action by performing the function of the coagulation Factor VIII without presenting a structural homology.9 It presents a dual specificity which allows it to bind to both the Factor IXa and Factor X, performing the required bridging activity for the launch of the coagulation cascade.2
Target Actions Organism ACoagulation factor IX cofactorHumans ACoagulation factor X activatorHumans - Absorption
Subcutaneous administration of Emicizumab presents a very high bioavailability ranging from 80.4% to 93.1% when administered subcutaneously in a dose of 1 mg/kg.6 In clinical trials, at the same dose, Emicizumab presented a linear exposure which concentration peaked 1-2 weeks after administration and presented a profile framed by a Cmax of 5.92 mcg/ml and an AUC of 304 mcg day/ml.1
After subcutaneous administration, the absorption half-life was 1.7 days and the pharmacokinetic profile seemed to be shared when the medication was administered in the abdomen, upper arm, and thigh.13
- Volume of distribution
The apparent volume of distribution is 11.4 L when administered subcutaneously and there are reports indicating that this value can increase with increasing body weight.6 When emicizumab is administered intravenously, the volume of distribution at steady state is 106 ml/kg.13
- Protein binding
As emicizumab is a monoclonal antibody acting on the bloodstream, the determination of protein binding studies is not required.
- Metabolism
Emicizumab is a monoclonal antibody and thus, it is thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.5
- Route of elimination
The elimination of Emicizumab was monophasic in clinical trials.1
- Half-life
Emcicizumab presents a long half-life ranging from 27.8 to 34.4 days.Label,1
- Clearance
The apparent clearance is 0.24 L/day when administered in multiple subcutaneous injections and there are reports indicating that this value can increase with increasing body weight.6
- Adverse Effects
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The administration of Emicizumab has reported cases of microangiopathy and thrombotic events with concomitant use of activated prothrombin complex concentrate at doses higher of 100 U/kg/24 hours. There are also reports of injection site reaction, headaches and arthralgia.10
Genotoxicity and carcinogenicity studies have not been performed as it is not expected that emicizumab can have any interaction with DNA, or chromosomal material.13
- 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 Emicizumab can be decreased when used in combination with Abciximab. Acenocoumarol The therapeutic efficacy of Emicizumab can be decreased when used in combination with Acenocoumarol. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Emicizumab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Emicizumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Emicizumab. - 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 Hemlibra Injection, solution 150 mg/ml Subcutaneous Roche Registration Gmb H 2020-12-16 Not applicable EU 
Hemlibra Injection, solution 300 mg/2mL Subcutaneous Genentech, Inc. 2023-03-16 Not applicable US 
Hemlibra Solution 150 mg / mL Subcutaneous Hoffmann La Roche 2018-11-27 Not applicable Canada 
Hemlibra Injection, solution 150 mg/ml Subcutaneous Roche Registration Gmb H 2020-12-16 Not applicable EU Hemlibra Injection, solution 30 mg/1mL Subcutaneous Genentech, Inc. 2017-11-16 Not applicable US
Categories
- ATC Codes
- B02BX06 — Emicizumab
- 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
- 7NL2E3F6K3
- CAS number
- 1610943-06-0
References
- General References
- Uchida N, Sambe T, Yoneyama K, Fukazawa N, Kawanishi T, Kobayashi S, Shima M: A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects. Blood. 2016 Mar 31;127(13):1633-41. doi: 10.1182/blood-2015-06-650226. Epub 2015 Dec 1. [Article]
- Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, Fukazawa N, Yoneyama K, Yoshida H, Nogami K: Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A. N Engl J Med. 2016 May 26;374(21):2044-53. doi: 10.1056/NEJMoa1511769. [Article]
- Chavin SI: Factor VIII: structure and function in blood clotting. Am J Hematol. 1984 Apr;16(3):297-306. [Article]
- Nogami K: Bispecific antibody mimicking factor VIII. Thromb Res. 2016 May;141 Suppl 2:S34-5. doi: 10.1016/S0049-3848(16)30361-9. [Article]
- Tabrizi MA, Tseng CM, Roskos LK: Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006 Jan;11(1-2):81-8. doi: 10.1016/S1359-6446(05)03638-X. [Article]
- 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. [Article]
- Roche news [Link]
- Bussiness wire [Link]
- Roche study [Link]
- Genentech professionals information [Link]
- FDA news [Link]
- FDA news [Link]
- Hemlibra (Emicizumab) EMA label [File]
- External Links
- 1989795
- Wikipedia
- Emicizumab
- FDA label
- Download (592 KB)
- MSDS
- Download (1.25 MB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Recruiting Not Available Hemophilia A 1 somestatus stop reason just information to hide 4 Active Not Recruiting Basic Science Moderate Hemophilia A / Severe Hemophilia A 1 somestatus stop reason just information to hide 4 Active Not Recruiting Prevention Hemophilia A / Immune Tolerance 1 somestatus stop reason just information to hide 4 Recruiting Treatment Factor VIII (FVIII) / Hemophilia A 1 somestatus stop reason just information to hide 4 Recruiting Treatment Factor VIII Deficiency, Congenital 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Subcutaneous 30 MG/ML Injection, solution Parenteral; Subcutaneous 150 MG/ML Injection, solution Parenteral; Subcutaneous 30 MG/ML Injection, solution Subcutaneous 105 mg/0.7mL Injection, solution Subcutaneous 12 mg/0.4mL Injection, solution Subcutaneous 150 mg/1mL Injection, solution Subcutaneous 30 mg/1mL Injection, solution Subcutaneous 300 mg/2mL Injection, solution Subcutaneous 60 mg/0.4mL Solution Subcutaneous 105 mg / 0.7 mL Solution Subcutaneous 150 mg / mL Solution Subcutaneous 30 mg / 1 mL Solution Subcutaneous 60 mg / 0.4 mL Injection, solution Subcutaneous Injection, solution Subcutaneous 150 mg/ml Injection, solution Subcutaneous 30 mg/mL Solution Subcutaneous 150 mg Solution Subcutaneous 30 mg Injection, solution 150 mg/1ml Injection, solution 30 mg/1ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 78ºC Ji-Hee, et al. Front Immunol, 7:394 (2016) boiling point (°C) Fab and Fc domains denaturates at 60 and 70 ºC respectively Arnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404 water solubility 50 mg/ml Human IgG purified. Product Information isoelectric point 6.6 - 7.2 Jin, et al. Electrophoresis. Sep;23(19):3385-91. (2002).
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Cofactor
- General 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, phospholipids, and factor VIIIa
- Specific Function
- Calcium ion binding
- Gene Name
- F9
- Uniprot ID
- P00740
- Uniprot Name
- Coagulation factor IX
- Molecular Weight
- 51778.11 Da
References
- Uchida N, Sambe T, Yoneyama K, Fukazawa N, Kawanishi T, Kobayashi S, Shima M: A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects. Blood. 2016 Mar 31;127(13):1633-41. doi: 10.1182/blood-2015-06-650226. Epub 2015 Dec 1. [Article]
- Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, Fukazawa N, Yoneyama K, Yoshida H, Nogami K: Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A. N Engl J Med. 2016 May 26;374(21):2044-53. doi: 10.1056/NEJMoa1511769. [Article]
- Chavin SI: Factor VIII: structure and function in blood clotting. Am J Hematol. 1984 Apr;16(3):297-306. [Article]
- Nogami K: Bispecific antibody mimicking factor VIII. Thromb Res. 2016 May;141 Suppl 2:S34-5. doi: 10.1016/S0049-3848(16)30361-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General 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. Factor Xa activates pro-inflammatory signaling pathways in a protease-activated receptor (PAR)-dependent manner (PubMed:24041930, PubMed:30568593, PubMed:34831181). Up-regulates expression of protease-activated receptors (PARs) F2R, F2RL1 and F2RL2 in dermal microvascular endothelial cells (PubMed:35738824). Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL6, in cardiac fibroblasts and umbilical vein endothelial cells in PAR-1 (F2R)-dependent manner (PubMed:30568593, PubMed:34831181). Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2, IL6, TNF-alpha/TNF, IL-1beta/IL1B, IL8/CXCL8 and IL18, in endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824, PubMed:9780208). Induces expression of adhesion molecules, such as ICAM1, VCAM1 and SELE, in endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824, PubMed:9780208). Increases expression of phosphorylated ERK1/2 in dermal microvascular endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824). Triggers activation of the transcription factor NF-kappa-B in dermal microvascular endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824). Up-regulates expression of plasminogen activator inhibitor 1 (SERPINE1) in atrial tissues (PubMed:24041930)
- Specific Function
- Calcium ion binding
- Gene Name
- F10
- Uniprot ID
- P00742
- Uniprot Name
- Coagulation factor X
- Molecular Weight
- 54731.255 Da
References
- Uchida N, Sambe T, Yoneyama K, Fukazawa N, Kawanishi T, Kobayashi S, Shima M: A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects. Blood. 2016 Mar 31;127(13):1633-41. doi: 10.1182/blood-2015-06-650226. Epub 2015 Dec 1. [Article]
- Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, Fukazawa N, Yoneyama K, Yoshida H, Nogami K: Factor VIII-Mimetic Function of Humanized Bispecific Antibody in Hemophilia A. N Engl J Med. 2016 May 26;374(21):2044-53. doi: 10.1056/NEJMoa1511769. [Article]
- Chavin SI: Factor VIII: structure and function in blood clotting. Am J Hematol. 1984 Apr;16(3):297-306. [Article]
- Nogami K: Bispecific antibody mimicking factor VIII. Thromb Res. 2016 May;141 Suppl 2:S34-5. doi: 10.1016/S0049-3848(16)30361-9. [Article]
Drug created at November 16, 2017 18:12 / Updated at June 03, 2022 07:24