Blinatumomab

Identification

Summary

Blinatumomab is an antineoplastic antibody used to treat Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Brand Names
Blincyto
Generic Name
Blinatumomab
DrugBank Accession Number
DB09052
Background

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.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
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
  • Blinatumomab
External IDs
  • AMG103
  • MEDI 538
  • MEDI-538
  • MEDI538
  • MT 103
  • MT-103
  • MT103

Pharmacology

Indication

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

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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
Humans
AT-cell surface glycoprotein CD3 delta chain
activator
Humans
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.

Adverse Effects
Adverseeffects
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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).
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.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Blinatumomab.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Blinatumomab.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Blinatumomab.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Blinatumomab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Blinatumomab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Blinatumomab.
AducanumabThe risk or severity of adverse effects can be increased when Blinatumomab is combined with Aducanumab.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Blinatumomab.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Blinatumomab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Blinatumomab.
Interactions
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Food Interactions
No interactions found.

Products

Products2
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dosage, form, labeller, route of administration, and marketing period.
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BlincytoSolution38.5 mcgIntravenousAmgen Europe B.V.2020-12-22Not applicableEU flag
BlincytoKit12.5 ug/1mLIntravenousAMGEN INC2014-12-18Not applicableUS flag
BlincytoPowder, for solution38.5 mcg / vialIntravenousAmgen2016-03-17Not applicableCanada flag

Categories

ATC Codes
L01XC19 — Blinatumomab
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
4FR53SIF3A
CAS number
853426-35-4

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. [Article]
  2. Garber K: Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801. doi: 10.1038/nrd4478. [Article]
KEGG Drug
D09325
PubChem Substance
347910400
RxNav
1597258
ChEMBL
CHEMBL1742992
Drugs.com
Drugs.com Drug Page
Wikipedia
Blinatumomab
FDA label
Download (242 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Not Yet RecruitingTreatmentPrecursor-B Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukemia (ALL)1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukemia (ALL) / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative1
3Active Not RecruitingTreatmentRecurrent B Acute Lymphoblastic Leukemia1
3CompletedTreatmentAcute Lymphoblastic Leukemia (ALL)1
3Not Yet RecruitingTreatmentAcute Lymphoblastic Leukemia (Philadelphia Chromosome Positive) / ALL, Adult / Philadelphia-Positive ALL1
3Not Yet RecruitingTreatmentNewly Diagnosed Philadelphia (Ph)-Negative B-cell Precursor Acute Lymphoblastic Leukemia (ALL)1
3RecruitingTreatmentAcute Lymphoblastic Leukemia (ALL)1
3RecruitingTreatmentB Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL11
3RecruitingTreatmentB Acute Lymphoblastic Leukemia / B Lymphoblastic Lymphoma / Down Syndrome (DS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous38.5 mcg/1vial
KitIntravenous12.5 ug/1mL
PowderIntravenous; Parenteral38.5 MICROGRAMMI
Powder, for solutionIntravenous38.5 mcg / vial
SolutionIntravenous38.5 mcg
InjectionIntravenous
InjectionParenteral
Injection, powder, lyophilized, for solutionIntravenous38.5 mcg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7235641No2007-06-262023-12-22US flag
US7575923No2009-08-182018-04-21US flag
US7635472No2009-12-222023-05-31US flag
US8247194No2012-08-212024-05-05US flag
US20120328618No2009-10-272029-10-27US flag
US20130323247No2008-11-072028-11-07US flag

Properties

State
Solid
Experimental Properties
Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Drug created on May 06, 2015 22:29 / Updated on September 16, 2021 13:04