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Identification
NameBlinatumomab
Accession NumberDB09052
TypeBiotech
GroupsApproved
Description

Blinatumomab is a BiTE-class (bi-specific T-cell engagers) constructed monoclonal antibody indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Blinatumomab is manufactured by Amgen Inc. and marketed under the brand Blincyto™. A full treatment regimen consisting of two cycles of four weeks each, is priced at $178 000 USD. Blinatumomab was approved in December 2014 under the FDA’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.

Protein structureDb09052
Related Articles
Protein chemical formulaC2367H3577N649O772S19
Protein average weight54100.0 Da
Sequences
>single chain variable fragment fusion protein 
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLIYDASNLVS
GIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFGGGTKLEIKGGGGSGGGG
SGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIWPG
DGDTNYNGKFKGKATLTADESSSTAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYW
GQGTTVTVSSGGGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL
EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYCARYYDDHYC
LDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPAIMSASPGEKVTMTCRASSS
VSYMNWYQQKSGTSPKRWIYDTSKVASGVPYRFSGSGSGTSYSLTISSMEAEDAATYYCQ
QWSSNPLTFGAGTKLELKHHHHHH
Download FASTA Format
SynonymsNot Available
External Identifiers
  • AMG103
  • MEDI 538
  • MEDI-538
  • MEDI538
  • MT 103
  • MT-103
  • MT103
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BlincytokitintravenousAmgen Inc2014-12-18Not applicableUs
Blincytopowder for solution38.5 mcgintravenousAmgen Canada Inc2016-03-17Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNII4FR53SIF3A
CAS number853426-35-4
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationIndicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
PharmacodynamicsNot Available
Mechanism of actionBlinatumomab is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. It activates endogenous T cells by connecting CD3 in the T-cell receptor (TCR) complex with CD19 on benign and malignant B cells. Blinatumomab mediates the formation of a synapse between the T cell and the tumor cell, upregulation of cell adhesion molecules, production of cytolytic proteins, release of inflammatory cytokines, and proliferation of T cells, which result in redirected lysis of CD19+ cells.
Related Articles
AbsorptionNot Available
Volume of distribution

4.52 L, standard deviation 2.89.

Protein bindingNot Available
Metabolism

The metabolic pathway of blinatumomab has not been characterized. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Route of eliminationNot Available
Half life2.11 hours, standard deviation 1.42.
Clearance

2.92 L/hour, standard deviation 2.83.

Toxicity- Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab as recommended. - Neurological toxicities, which may be severe, life-threatening, or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab as recommended. - In patients receiving blinatumomab in clinical trials, serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections were observed in approximately 25% of patients, some of which were life-threatening or fatal. - Tumor lysis syndrome (TLS), which may be life-threatening or fatal, has been observed in patients. - Neutropenia and febrile neutropenia, including life-threatening cases, have been observed in patients. - Treatment with blinatumomab was associated with transient elevations in liver enzymes. - Cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving blinatumomab, especially in patients with prior treatment with cranial irradiation and antileukemic chemotherapy (including systemic high-dose methotrexate or intrathecal cytarabine).
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Kitintravenous
Powder for solutionintravenous38.5 mcg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US20120328618 No2009-10-272029-10-27Us
US20130323247 No2008-11-072028-11-07Us
US7235641 No2003-12-222023-12-22Us
US7575923 No1998-04-212018-04-21Us
US7635472 No2003-05-312023-05-31Us
US8247194 No2004-05-052024-05-05Us
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General References
  1. Zugmaier G, Klinger M, Schmidt M, Subklewe M: Clinical overview of anti-CD19 BiTE((R)) and ex vivo data from anti-CD33 BiTE((R)) as examples for retargeting T cells in hematologic malignancies. Mol Immunol. 2015 Oct;67(2 Pt A):58-66. doi: 10.1016/j.molimm.2015.02.033. Epub 2015 Apr 13. [PubMed:25883042 ]
  2. Garber K: Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801. doi: 10.1038/nrd4478. [PubMed:25359367 ]
External Links
ATC CodesL01XC19
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (242 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
ClozapineThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Clozapine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Blinatumomab.
LeflunomideThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Leflunomide.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Blinatumomab.
NatalizumabThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Blinatumomab.
RoflumilastRoflumilast may increase the immunosuppressive activities of Blinatumomab.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Blinatumomab.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Blinatumomab.
TofacitinibBlinatumomab may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Blinatumomab.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
activator
General Function:
Receptor signaling protein activity
Specific Function:
Assembles with the antigen receptor of B-lymphocytes in order to decrease the threshold for antigen receptor-dependent stimulation.
Gene Name:
CD19
Uniprot ID:
P15391
Molecular Weight:
61127.985 Da
References
  1. Zugmaier G, Klinger M, Schmidt M, Subklewe M: Clinical overview of anti-CD19 BiTE((R)) and ex vivo data from anti-CD33 BiTE((R)) as examples for retargeting T cells in hematologic malignancies. Mol Immunol. 2015 Oct;67(2 Pt A):58-66. doi: 10.1016/j.molimm.2015.02.033. Epub 2015 Apr 13. [PubMed:25883042 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
activator
General Function:
Transmembrane signaling receptor activity
Specific Function:
The CD3 complex mediates signal transduction.
Gene Name:
CD3D
Uniprot ID:
P04234
Molecular Weight:
18929.38 Da
References
  1. Zugmaier G, Klinger M, Schmidt M, Subklewe M: Clinical overview of anti-CD19 BiTE((R)) and ex vivo data from anti-CD33 BiTE((R)) as examples for retargeting T cells in hematologic malignancies. Mol Immunol. 2015 Oct;67(2 Pt A):58-66. doi: 10.1016/j.molimm.2015.02.033. Epub 2015 Apr 13. [PubMed:25883042 ]
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Drug created on May 06, 2015 16:29 / Updated on August 17, 2016 12:24