Identification

Name
Blinatumomab
Accession Number
DB09052
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
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 structure
Db09052
Protein chemical formula
C2367H3577N649O772S19
Protein average weight
54100.0 Da
Sequences
>single chain variable fragment fusion protein 
DIQLTQSPASLAVSLGQRATISCKASQSVDYDGDSYLNWYQQIPGQPPKLLIYDASNLVS
GIPPRFSGSGSGTDFTLNIHPVEKVDAATYHCQQSTEDPWTFGGGTKLEIKGGGGSGGGG
SGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIWPG
DGDTNYNGKFKGKATLTADESSSTAYMQLSSLASEDSAVYFCARRETTTVGRYYYAMDYW
GQGTTVTVSSGGGGSDIKLQQSGAELARPGASVKMSCKTSGYTFTRYTMHWVKQRPGQGL
EWIGYINPSRGYTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYCARYYDDHYC
LDYWGQGTTLTVSSVEGGSGGSGGSGGSGGVDDIQLTQSPAIMSASPGEKVTMTCRASSS
VSYMNWYQQKSGTSPKRWIYDTSKVASGVPYRFSGSGSGTSYSLTISSMEAEDAATYYCQ
QWSSNPLTFGAGTKLELKHHHHHH
Download FASTA Format
Synonyms
Not Available
External IDs
AMG103 / MEDI 538 / MEDI-538 / MEDI538 / MT 103 / MT-103 / MT103
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BlincytoPowder, for solution38.5 mcgIntravenousAmgen2016-03-17Not applicableCanada
BlincytoKitIntravenousAmgen2014-12-18Not applicableUs
Categories
UNII
4FR53SIF3A
CAS number
853426-35-4

Pharmacology

Indication

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

Structured Indications
Pharmacodynamics
Not 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.

TargetActionsOrganism
AB-lymphocyte antigen CD19
activator
Human
AT-cell surface glycoprotein CD3 delta chain
activator
Human
Absorption
Not Available
Volume of distribution

4.52 L, standard deviation 2.89.

Protein binding
Not 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 elimination
Not 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Blinatumomab.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Blinatumomab.Experimental
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Blinatumomab.Approved, Investigational, Withdrawn
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Anthrax immune globulin human.Approved
Bacillus calmette-guerin substrain connaught live antigenThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Bacillus calmette-guerin substrain connaught live antigen.Approved, Investigational
Bacillus calmette-guerin substrain tice live antigenThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Bacillus calmette-guerin substrain tice live antigen.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine 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
Clostridium tetani toxoid antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Blinatumomab is combined with Clostridium tetani toxoid antigen (formaldehyde inactivated).Approved
ClozapineThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Clozapine.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Blinatumomab is combined with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated).Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Blinatumomab.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Blinatumomab.Experimental
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, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Blinatumomab.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) 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
GitoformateGitoformate may decrease the cardiotoxic activities of Blinatumomab.Experimental
Hepatitis A VaccineThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Hepatitis A Vaccine.Approved
Hepatitis B Vaccine (Recombinant)The risk or severity of adverse effects can be increased when Blinatumomab is combined with Hepatitis B Vaccine (Recombinant).Approved, Withdrawn
Human rabies virus immune globulinThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Human rabies virus immune globulin.Approved
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
Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Blinatumomab is combined with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated).Approved
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Blinatumomab.Experimental
LeflunomideThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Leflunomide.Approved, Investigational
MetamizoleThe risk or severity of myelosuppression can be increased when Metamizole is combined with Blinatumomab.Approved, Investigational, Withdrawn
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Blinatumomab.Experimental
NatalizumabThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Natalizumab.Approved, Investigational
OcrelizumabOcrelizumab may increase the immunosuppressive activities of Blinatumomab.Approved, Investigational
OleandrinOleandrin may decrease the cardiotoxic activities of Blinatumomab.Experimental, Investigational
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
PeruvosidePeruvoside may decrease the cardiotoxic activities of Blinatumomab.Experimental
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Blinatumomab.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Blinatumomab.Experimental
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Rabies virus inactivated antigen, A.Approved, Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Blinatumomab.Approved, Investigational
RindopepimutThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Rindopepimut.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Blinatumomab.Approved
Rotavirus VaccineThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Rotavirus Vaccine.Approved
Rubella virus vaccineThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Rubella virus vaccine.Approved, Investigational
Salmonella typhi ty2 vi polysaccharide antigenThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Salmonella typhi ty2 vi polysaccharide antigen.Approved
Salmonella typhi ty21a live antigenThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Salmonella typhi ty21a live antigen.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Blinatumomab.Approved, Investigational
SRP 299The risk or severity of adverse effects can be increased when Blinatumomab is combined with SRP 299.Investigational
TacrolimusTacrolimus may increase the immunosuppressive activities of Blinatumomab.Approved, Investigational
TecemotideThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Tecemotide.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
Varicella Zoster Vaccine (Live/Attenuated)The risk or severity of adverse effects can be increased when Blinatumomab is combined with Varicella Zoster Vaccine (Live/Attenuated).Approved
Yellow Fever VaccineThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Yellow Fever Vaccine.Approved, Investigational
Food Interactions
Not Available

References

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
KEGG Drug
D09325
PubChem Substance
347910400
ChEMBL
CHEMBL1742992
Drugs.com
Drugs.com Drug Page
Wikipedia
Blinatumomab
ATC Codes
L01XC19 — Blinatumomab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (242 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B-cell Non Hodgkin's Lymphoma / Pre B-Cell Acute Lymphoblastic Leukaemia1
0RecruitingTreatmentMultiple Myeloma (MM)1
1CompletedTreatmentNon-Hodgkin's Lymphoma, Relapsed1
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 B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin 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 Lymphoma / Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma / Refractory Burkitt Lymphoma / Refractory Diffuse Large B-Cell Lymphoma / Refractory Follicular Lymphoma / Refractory Mantle Cell Lymphoma / Refractory Small Lymphocytic Lymphoma1
1RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
1RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentRelapsed or Refractory Diffuse Large B Cell Lymphoma (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, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemias1
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 Lymphocytic Leukemia (ALL) / Philadelphia Chromosome-Negative B-Cell Precursor1
2Not Yet RecruitingTreatmentHigh-risk Diffuse Large B-Cell Lymphoma1
2RecruitingTreatmentALL, Recurrent, Adult1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)2
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) / Chronic Myeloid Leukemia (CML) / Granulocytic Sarcoma / Juvenile Myelomonocytic Leukemia (JMML) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes (MDS) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemias1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic1
2RecruitingTreatmentAcute Lymphocytic Leukemia (ALL) / Leukemias1
2RecruitingTreatmentAdult B Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive1
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, 3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Lymphoblastic Lymphoma1
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
Not AvailableNot Yet RecruitingNot AvailableAcute Lymphoblastic Leukaemias (ALL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
KitIntravenous
Powder, for solutionIntravenous38.5 mcg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7235641No2003-12-222023-12-22Us
US7575923No1998-04-212018-04-21Us
US7635472No2003-05-312023-05-31Us
US8247194No2004-05-052024-05-05Us
US20120328618No2009-10-272029-10-27Us
US20130323247No2008-11-072028-11-07Us

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

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

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 April 22, 2018 23:40