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 IDs AMG103 / MEDI 538 / MEDI-538 / MEDI538 / MT 103 / MT-103 / MT103
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BlincytoPowder, for solution38.5 mcgIntravenousAmgen2016-03-17Not applicableCanada
BlincytoKitIntravenousAmgen2014-12-18Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII4FR53SIF3A
CAS number853426-35-4
Pharmacology
Indication

Indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Structured Indications
PharmacodynamicsNot Available
Mechanism of action

Blinatumomab 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.

TargetKindPharmacological actionActionsOrganismUniProt ID
B-lymphocyte antigen CD19Proteinyes
activator
HumanP15391 details
T-cell surface glycoprotein CD3 delta chainProteinyes
activator
HumanP04234 details
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 life

2.11 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
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Blinatumomab.Approved
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Blinatumomab.Investigational
BelimumabThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Belimumab.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Blinatumomab.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Blinatumomab.Approved
ClozapineThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Clozapine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Blinatumomab.Approved, Investigational
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Blinatumomab.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Blinatumomab.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Blinatumomab.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Blinatumomab.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Blinatumomab.Approved, Investigational
FingolimodBlinatumomab may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe risk or severity of adverse effects can be increased when Blinatumomab is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Blinatumomab is combined with GI-5005.Investigational
INGN 201The risk or severity of adverse effects can be increased when Blinatumomab is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Blinatumomab is combined with INGN 225.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Leflunomide.Approved, Investigational
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Blinatumomab.Withdrawn
NatalizumabThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Natalizumab.Approved, Investigational
OleandrinAnvirzel may decrease the cardiotoxic activities of Blinatumomab.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Blinatumomab.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Blinatumomab.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Blinatumomab.Approved, Investigational
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Rabies vaccine.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Blinatumomab.Approved
RindopepimutThe risk or severity of adverse effects can be increased when Blinatumomab is combined with CDX-110.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Blinatumomab.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Blinatumomab.Approved
SRP 299The risk or severity of adverse effects can be increased when Blinatumomab is combined with SRP 299.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Blinatumomab.Approved, Investigational
TG4010The risk or severity of adverse effects can be increased when Blinatumomab is combined with TG4010.Investigational
TofacitinibBlinatumomab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Blinatumomab.Approved, Investigational
Food InteractionsNot 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 — Blinatumomab
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (242 KB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B-cell Non Hodgkin's Lymphoma / Pre B-Cell Acute Lymphoblastic Leukaemia1
0RecruitingTreatmentMultiple Myeloma (MM)1
1CompletedTreatmentNon-Hodgkin's Lymphoma, Relapsed1
1Not Yet RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentB Acute Lymphoblastic Leukemia / B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / CD19-Positive Neoplastic Cells Present / Mixed Phenotype Acute Leukemia (MPAL) / Mixed Phenotype Acute Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL11
1RecruitingTreatmentB-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma / CD19 Positive / Mediastinal Lymphoma / Recurrent Adult Burkitt Lymphoma / Recurrent Burkitt Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Small Lymphocytic Lymphoma1
1RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
1WithdrawnTreatmentLymphoma, B-Cell / Non-Hodgkin's Lymphoma (NHL)1
1, 2Active Not RecruitingTreatmentRelapsed Refractory B Precursor Acute Lymphoblastic Leukemia / Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL)1
1, 2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1, 2RecruitingTreatmentB-Cell Acute Lymphoblastic Leukemia, Adult1
1, 2WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL)1
2Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2Active Not RecruitingTreatmentB-All1
2Active Not RecruitingTreatmentB-cell Acute Lymphoblastic Leukemia1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2CompletedTreatmentRelapsed/Refractory Philadelphia Positive B-precursor Acute Lymphoblastic Leukemia / Relapsed/Refractory Philadelphia Positive B-precursor ALL1
2Not Yet RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2Not Yet RecruitingTreatmentAdult B Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive1
2RecruitingTreatmentALL, Recurrent, Adult1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myeloid Leukaemias (AML) / Chronic Myeloid Leukemia (CML) / Granulocytic Sarcoma / Juvenile Myelomonocytic Leukemia (JMML) / Myelodysplastic Syndromes (MDS) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia / B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative / Philadelphia Chromosome Positive / Recurrent Adult Acute Lymphoblastic Leukemia / Refractory Adult Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemias1
2RecruitingTreatmentAcute Lymphocytic Leukemia (ALL) / Leukemias1
2RecruitingTreatmentHematopoietic/Lymphoid Cancer / Richter's Transformation1
2RecruitingTreatmentHigh-risk Diffuse Large B-Cell Lymphoma / High-risk Diffuse Large B-Cell Lymphoma (DLBCL)1
2RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
2, 3RecruitingTreatmentB-cell Non Hodgkin's Lymphoma1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult B Acute Lymphoblastic Leukemia / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative / BCR/ABL1 Fusion Protein Negative / Untreated Adult Acute Lymphoblastic Leukemia1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia1
3TerminatedTreatmentAdult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia / Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia1
Not AvailableAvailableNot AvailableRelapsed/Refractory B-precursor Acute Lymphoblastic Leukemia / Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL)1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
KitIntravenous
Powder, for solutionIntravenous38.5 mcg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7235641 No2003-12-222023-12-22Us
US7575923 No1998-04-212018-04-21Us
US7635472 No2003-05-312023-05-31Us
US8247194 No2004-05-052024-05-05Us
US20120328618 No2009-10-272029-10-27Us
US20130323247 No2008-11-072028-11-07Us
Properties
StateSolid
Experimental PropertiesNot Available
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

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
Uniprot Name:
B-lymphocyte antigen CD19
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
Uniprot Name:
T-cell surface glycoprotein CD3 delta chain
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 ]
Drug created on May 06, 2015 16:29 / Updated on August 17, 2016 12:24