Glatiramer Acetate

Identification

Name
Glatiramer Acetate
Accession Number
DB05259  (APRD00999)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Peptides
Description

Glatiramer acetate consists of the acetate salts of synthetic polypeptides, containing four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine with an average molar fraction of 0.141, 0.427, 0.095, and 0.338, respectively. The average molecular weight of glatiramer acetate is 5,000-9,000 daltons. It is an immunomodulator, licensed in much of the world for reduced frequency of relapses in relapsing-remitting multiple sclerosis.

Protein chemical formula
C254H422N70O72
Protein average weight
7000.0 Da (range 5000-9000)
Sequences
>Example Glatiramer peptide
EAYKAAEKAYAAKEAAKEAAKAKAEKKAAYAKAKAAKYEKKAKKAAAEYKKK
Download FASTA Format
Synonyms
  • COP-1
  • Copolymer-1
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CopaxonePowder, for solution20 mgSubcutaneousTeva Pharmaceutical Industries1997-10-142011-04-28Canada
CopaxoneSolution40 mgSubcutaneousTeva2016-08-26Not applicableCanada
CopaxoneSolution20 mgSubcutaneousTeva2002-05-01Not applicableCanada
CopaxoneInjection, solution20 mg/mLSubcutaneousTeva Neuroscience, Inc.2008-04-28Not applicableUs
CopaxoneInjection, solution40 mg/mLSubcutaneousTeva Neuroscience, Inc.2014-01-29Not applicableUs
GlatectSolution20 mgSubcutaneousPharmascience Inc2017-08-21Not applicableCanada
Teva-glatiramer AcetateSolution20 mgSubcutaneousTevaNot applicableNot applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Glatiramer AcetateInjection, solution20 mg/mLSubcutaneousMylan Pharmaceuticals2017-10-04Not applicableUs
Glatiramer AcetateInjection, solution40 mg/mLSubcutaneousMylan Pharmaceuticals2017-10-04Not applicableUs
GlatopaInjection, solution20 mg/mLSubcutaneousSandoz2015-06-18Not applicableUs
Categories
UNII
5M691HL4BO
CAS number
147245-92-9

Pharmacology

Indication

For reduction of the frequency of relapses in patients with Relapsing-Remitting Multiple Sclerosis.

Structured Indications
Pharmacodynamics

Glatiramer acetate was originally designed to mimic a protein in myelin, called myelin basic protein, with the intention of inducing EAE (an animal model of MS). Quite to the contrary, it was found to suppress the disease and as a result came to be trialed in human MS. There is some evidence that Glatiramer acetate converts the body's immune response from a Th1 type to a Th2 one, promotes suppressor T cells or acts as an altered peptide ligand. Studies in animals and in vitro systems suggest that upon its administration, glatiramer acetate-specific suppressor T-cells are induced and activated in the periphery. Some fraction of the injected material, either intact or partially hydrolyzed, is presumed to enter the lymphatic circulation, enabling it to reach regional lymph nodes, and some may enter the systemic circulation intact.

Mechanism of action

Glatiramer acetate (GA) exhibits strong and promiscuous binding to MHC molecules (HLA DRB1* variants) and consequent competition with various myelin antigens for their presentation to T cells. A further aspect of its action is potent induction of specific suppressor cells of the T helper 2 (Th2) type that migrate to the brain and lead to in situ bystander suppression. Furthermore, the GA-specific cells in the brain express the anti-inflammatory cytokines IL-10 and transforming growth factor beta, in addition to brain-derived neurotrophic factor, whereas they do not express the inflammatory cytokine IFN-gamma. Recent evidence also suggests that Glatiramer acetate directly inhibits dendritic cells and monocytes - both of which are circulating antigen presenting cells.

TargetActionsOrganism
UHLA class II histocompatibility antigen, DRB1-1 beta chain
binder
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hydrolyzed by proteases

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Adverse reactions include injection site reactions, vasodilatation, chest pain, asthenia, infection, pain, nausea, arthralgia, anxiety, and hypertonia.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Glatiramer Acetate.Investigational
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Glatiramer Acetate.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Glatiramer Acetate.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Glatiramer Acetate.Approved
FingolimodGlatiramer Acetate may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Glatiramer Acetate.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Glatiramer Acetate.Investigational
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Glatiramer Acetate.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Glatiramer Acetate.Approved, Withdrawn
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Glatiramer Acetate.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Glatiramer Acetate.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Glatiramer Acetate is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Glatiramer Acetate is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Glatiramer Acetate.Approved, Investigational
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Glatiramer Acetate is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Glatiramer Acetate.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Glatiramer Acetate.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Glatiramer Acetate.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Glatiramer Acetate.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Glatiramer Acetate.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Glatiramer Acetate.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Glatiramer Acetate.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Glatiramer Acetate.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Glatiramer Acetate.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Glatiramer Acetate.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Glatiramer Acetate.Investigational
TofacitinibGlatiramer Acetate may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Glatiramer Acetate.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Glatiramer Acetate.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Glatiramer Acetate.Approved
Food Interactions
Not Available

References

Synthesis Reference

Tsung-Yu Hsiao, Meng-Fen Ho, "Synthesis of Glatiramer Acetate." U.S. Patent US20100036092, issued February 11, 2010.

US20100036092
General References
  1. Weber MS, Hohlfeld R, Zamvil SS: Mechanism of action of glatiramer acetate in treatment of multiple sclerosis. Neurotherapeutics. 2007 Oct;4(4):647-53. [PubMed:17920545]
  2. Arnon R, Aharoni R: Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications. Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14593-8. Epub 2004 Sep 15. [PubMed:15371592]
  3. Francis DA: Glatiramer acetate (Copaxone). Int J Clin Pract. 2001 Jul-Aug;55(6):394-8. [PubMed:11501229]
  4. Li Q, Milo R, Panitch H, Swoveland P, Bever CT Jr: Glatiramer acetate blocks the activation of THP-1 cells by interferon-gamma. Eur J Pharmacol. 1998 Jan 26;342(2-3):303-10. [PubMed:9548401]
External Links
PubChem Substance
46505299
ChEMBL
CHEMBL1201507
Therapeutic Targets Database
DAP001315
PharmGKB
PA449760
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Glatiramer_acetate
ATC Codes
L03AX13 — Glatiramer acetate
AHFS Codes
  • 92:20.00 — Immunomodulatory Agents
FDA label
Download (558 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAutoimmune Diseases / Disseminated or Multiple Sclerosis Nos / Disseminated Sclerosis / Multiple Sclerosis, Acute Relapsing / Multiple Sclerosis, Chronic Progressive / Multiple Sclerosis, Primary Progressive1
1SuspendedTreatmentDry Age Related Macular Degeneration1
1Unknown StatusTreatmentRett's Syndrome1
2CompletedDiagnosticRelapsing Remitting Multiple Sclerosis (RRMS)1
2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2CompletedTreatmentDisseminated Sclerosis3
2CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)4
2TerminatedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
2Unknown StatusTreatmentCrohns Disease1
2Unknown StatusTreatmentRett's Syndrome1
2, 3Not Yet RecruitingTreatmentProgressive Multiple Sclerosis1
2, 3RecruitingTreatmentDisseminated Sclerosis / Relapsing Remitting Multiple Sclerosis (RRMS)1
2, 3Unknown StatusTreatmentMacular Degeneration1
3CompletedNot AvailableDisseminated Sclerosis1
3CompletedTreatmentDisseminated Sclerosis2
3CompletedTreatmentOptic Neuritis1
3CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)8
3TerminatedNot AvailableRelapsing Remitting Multiple Sclerosis (RRMS)1
3TerminatedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
3Unknown StatusPreventionGlaucoma, Angle-closure, Primary, Acute1
4Active Not RecruitingTreatmentDisseminated Sclerosis1
4Active Not RecruitingTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
4CompletedPreventionDisseminated Sclerosis1
4CompletedTreatmentDisseminated Sclerosis3
4CompletedTreatmentRelapsing Forms of Multiple Sclerosis1
4CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)3
4TerminatedNot AvailableRelapsing Remitting Multiple Sclerosis (RRMS)1
4TerminatedPreventionRelapsing Remitting Multiple Sclerosis (RRMS)1
4TerminatedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
4Unknown StatusTreatmentDisseminated Sclerosis2
4Unknown StatusTreatmentRetinopathy, Diabetic1
Not AvailableCompletedNot AvailableDisseminated Sclerosis2
Not AvailableCompletedNot AvailableDisseminated Sclerosis / Low Bone Density1
Not AvailableCompletedDiagnosticDisseminated Sclerosis1
Not AvailableCompletedTreatmentAutoimmune Diseases / Disseminated Sclerosis1
Not AvailableRecruitingNot AvailableDisseminated Sclerosis1
Not AvailableRecruitingNot AvailableRelapsing Remitting Multiple Sclerosis (RRMS)1
Not AvailableUnknown StatusTreatmentDisseminated Sclerosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous20 mg/mL
Injection, solutionSubcutaneous40 mg/mL
Powder, for solutionSubcutaneous20 mg
SolutionSubcutaneous20 mg
SolutionSubcutaneous40 mg
Prices
Unit descriptionCostUnit
Copaxone 20 mg/ml Kit 20 mg Solution, 1 Box = 30 Pre-Filled Syringes3775.25USD box
Copaxone 20 mg injection kit2264.26USD kit
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5981589No1994-05-242014-05-24Us
CA2191088No2004-09-282015-05-23Canada
US8232250No2010-08-192030-08-19Us
US8399413No2010-08-192030-08-19Us
US8969302No2010-08-192030-08-19Us
US9155776No2010-08-192030-08-19Us
US9402874No2010-08-192030-08-19Us

Properties

State
Liquid
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
Unknown
Actions
Binder
General Function
Virus receptor activity
Specific Function
Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding ...
Gene Name
HLA-DRB1
Uniprot ID
P04229
Uniprot Name
HLA class II histocompatibility antigen, DRB1-1 beta chain
Molecular Weight
29913.945 Da
References
  1. Arnon R, Aharoni R: Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications. Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14593-8. Epub 2004 Sep 15. [PubMed:15371592]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on November 18, 2007 11:22 / Updated on November 19, 2017 20:34