Identification
- Summary
Glatiramer is an immunomodulator used to reduce the frequency of relapses in Multiple Sclerosis (MS).
- Brand Names
- Copaxone, Glatect, Glatopa
- Generic Name
- Glatiramer
- DrugBank Accession Number
- DB05259
- Background
Glatiramer acetate is a mix of synthetic polypeptides that includes L-glutamic acid, L-alanine, L-tyrosine, and L-lysine at an average molar fraction of 0.141, 0.427, 0.095, and 0.338, respectively.9 Since glatiramer acetate is a heterogeneous drug, there is limited information about its physicochemical properties.5 Originally, glatiramer acetate was designed as a stimulant of myelin basic protein (MBP), a myelin antigen involved in the development of multiple sclerosis (MS), to induce experimental autoimmune encephalitis (MS animal model).5 However, the opposite was observed. Glatiramer acetate exhibits several immunomodulatory effects and reduces the relapse rate of relapsing-remitting multiple sclerosis (RRMS) by 30%.5 Along with human interferon beta, teriflunomide, and dimethyl fumarate, glatiramer acetate is a first-line drug for patients with MS.8 It was approved by the FDA in 1996, and a generic version became available in 2017.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Peptides - Protein Chemical Formula
- (C5H9NO4•C3H7NO2•C6H14N2O2•C9H11NO3)x•xC2H4O2
- Protein Average Weight
- 7000.0 Da (Range 5000-9000)
- Sequences
>Example Glatiramer peptide EAYKAAEKAYAAKEAAKEAAKAKAEKKAAYAKAKAAKYEKKAKKAAAEYKKK
Download FASTA FormatReferences:
- Qi GB, Gao YJ, Wang L, Wang H: Self-Assembled Peptide-Based Nanomaterials for Biomedical Imaging and Therapy. Adv Mater. 2018 May;30(22):e1703444. doi: 10.1002/adma.201703444. Epub 2018 Feb 20. [Article]
- Synonyms
- (T,G)-A-L
- COP 1
- COP-1
- Copolymer I (synthetic peptide)
- Copolymer-1
Pharmacology
- Indication
Glatiramer acetate is indicated for the treatment of relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.9
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Glatiramer acetate is a mix of synthetic polypeptides that includes four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine, and L-lysine. This drug is indicated for the treatment of relapsing multiple sclerosis (MS) due to its ability to modify immune processes involved in the pathogenesis of this disease. Intact and large fragments of glatiramer acetate are recognized by glatiramer acetate-reactive antibodies. In vitro and in vivo studies suggest that upon its administration, glatiramer acetate-specific suppressor T-cells are induced and activated in the periphery. 9 A fraction of intact or partially hydrolyzed glatiramer acetate enters lymphatic circulation and is able to reach the lymph nodes.9 Compared to placebo and IFNb-1a, patients with relapsing-remitting MS receiving 20 mg/mL of glatiramer acetate once a day had significantly lower annualized relapse rates. Similar outcomes were observed in MS patients taking 40 mg/mL of glatiramer acetate three times a week.7
Some of the patients treated with glatiramer acetate (approximately 16%) have developed immediate post-injection reactions. Most of these cases are transient and do not require treatment, but there have been reports of patients requiring emergency medical care.9 Patients taking glatiramer acetate may also experience chest pain, injection site side effects such as localized lipoatrophy and skin necrosis, and hepatic injury.9 Since glatiramer acetate modifies immune response, it may interfere with immune function.9
- Mechanism of action
The mechanism of action of glatiramer acetate has not been fully elucidated; however, it is thought to act by modifying immune processes involved in the pathogenesis of multiple sclerosis (MS).9 MS is characterized by damage to the myelin layer that covers nerve cells (demyelination) and axonal degeneration.2,6 Also, it has been suggested that the myelin basic protein (MBP), a myelin autoantigen, plays a role in the development of MS.2
Several mechanisms of action have been proposed. For instance, glatiramer acetate binds strongly to several major histocompatibility complex (MHC) class II molecules on MBP-specific antigen-presenting cells, preventing MBP from stimulating these cells.2,7 Glatiramer acetate also has the ability to shift the immune system from a pro-inflammatory to an anti-inflammatory pattern. It inhibits the secretion of pro-inflammatory cytokines (IL-2, IL-12, IFNγ, TNF) released by T helper 1 (Th1) cells, and induces T helper 2 (Th2) suppressor cells that are able to cross the blood-brain barrier and produce anti-inflammatory cytokines (IL-4, IL-5, IL-13, IL-10, TGF-β).6,7 It has also been suggested that glatiramer acetate induces the production of T-regulatory cells associated with the suppression of MS, such as CD4+, CD8+ and CD4+CD25+ cells.1,7
Target Actions Organism UHLA class II histocompatibility antigen, DRB1-1 beta chain binderHumans UHLA class II histocompatibility antigen, DRB1-15 beta chain binderHumans UHLA class II histocompatibility antigen, DRB1-4 beta chain binderHumans - Absorption
After subcutaneous administration, most glatiramer acetate is rapidly absorbed and hydrolyzed locally.9 In 7 out of 9 healthy volunteers that received 60 mg of glatiramer acetate subcutaneously, the Cmax ranged from 69 to 126 ng/mL, while the other two subjects showed significantly higher values (605 and 301 ng/mL).10 AUC values showed great variability, ranging from 1,644 to 67,532 min⋅ng/mL.10 The Tmax of glatiramer acetate went from 15 to 30 min, and in all subjects, glatiramer acetate levels returned to baseline after 30-60 min.5,10 In healthy volunteers given 60 mg of glatiramer acetate subcutaneously, immunorecognizable fragments were no longer detected after 24 hours.6,10 The systemic bioavailability of glatiramer acetate is considered to be minimal.5 The pharmacokinetic parameters of glatiramer acetate in multiple sclerosis (MS) patients have not been determined.5
- Volume of distribution
Not available.
- Protein binding
Glatiramer acetate is highly bound to plasma proteins.6
- Metabolism
Glatiramer acetate is a mixture of synthetic polypeptides hydrolyzed by proteases.6,9
- Route of elimination
In vivo studies have shown that glatiramer acetate is mainly excreted through urine.6
- Half-life
Not available.
- Clearance
Not available.
- Adverse Effects
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In mice given 60 mg/kg/day of glatiramer acetate subcutaneously (15 times the human therapeutic dose of 20 mg/day on a mg/m2 basis), glatiramer acetate did not increase systemic neoplasms. Similar results were obtained in rats given 30 mg/kg/day of glatiramer acetate subcutaneously (15 times the human therapeutic dose of 20 mg/day on a mg/m2 basis).9 In vitro studies suggest that glatiramer acetate is non-mutagenic. No adverse effects were observed on reproductive or developmental parameters during in vivo studies.9 Overdose information regarding glatiramer acetate is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as hepatic injury, lipoatrophy and skin necrosis at the injection site.9 Symptomatic and supportive measures are recommended.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Glatiramer. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Glatiramer. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Glatiramer. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Glatiramer. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Glatiramer. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Glatiramer. Allogeneic processed thymus tissue The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Glatiramer. Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Glatiramer. Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Glatiramer. Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Glatiramer. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Glatiramer acetate 5M691HL4BO 147245-92-9 Not applicable - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Copaxone Powder, for solution 20 mg / vial Subcutaneous Teva Pharmaceutical Industries 1997-10-14 2011-04-28 Canada 
Copaxone Injection 20 mg/1mL Subcutaneous Sanofi Aventis 2002-04-22 2010-01-31 US 
Copaxone Solution 40 mg / mL Subcutaneous TEVA Canada Limited 2016-08-26 Not applicable Canada Copaxone Injection, solution 40 mg/1mL Subcutaneous Teva Neuroscience, Inc. 2014-01-29 Not applicable US Copaxone Solution 40 mg / mL Subcutaneous TEVA Canada Limited Not applicable Not applicable Canada Copaxone Solution 20 mg / mL Subcutaneous TEVA Canada Limited 2002-05-01 Not applicable Canada Copaxone Injection, solution 20 mg/1mL Subcutaneous Teva Neuroscience, Inc. 2008-04-28 Not applicable US Glatect Solution 20 mg / mL Subcutaneous Pharmascience Inc 2017-08-21 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Glatiramer Acetate Injection, solution 20 mg/1mL Subcutaneous Mylan Pharmaceuticals Inc. 2017-10-04 Not applicable US Glatiramer Acetate Injection, solution 40 mg/1mL Subcutaneous Mylan Pharmaceuticals Inc. 2017-10-04 Not applicable US Glatopa Injection, solution 20 mg/1mL Subcutaneous Sandoz Inc 2015-06-18 Not applicable US Glatopa Injection, solution 20 mg/1mL Subcutaneous bryant ranch prepack 2015-06-18 Not applicable US Glatopa Injection, solution 40 mg/1mL Subcutaneous bryant ranch prepack 2018-02-12 Not applicable US Glatopa Injection, solution 40 mg/1mL Subcutaneous Sandoz Inc 2018-02-12 Not applicable US Teva-glatiramer Acetate Solution 20 mg / mL Subcutaneous TEVA Canada Limited Not applicable Not applicable Canada Teva-glatiramer Acetate Solution 40 mg / mL Subcutaneous TEVA Canada Limited Not applicable Not applicable Canada
Categories
- ATC Codes
- L03AX13 — Glatiramer acetate
- 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
- U782C039QP
- CAS number
- 28704-27-0
References
- Synthesis Reference
Dolitzky, BZ. (2006). Process for producing polypeptide mixtures using hydrogenolysis (U.S. Patent No. US 2006/0172942 A1). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/b6/b3/7d/a80568fe5c6998/US20060172942A1.pdf
US20100036092- General References
- Weber MS, Hohlfeld R, Zamvil SS: Mechanism of action of glatiramer acetate in treatment of multiple sclerosis. Neurotherapeutics. 2007 Oct;4(4):647-53. [Article]
- 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. [Article]
- Francis DA: Glatiramer acetate (Copaxone). Int J Clin Pract. 2001 Jul-Aug;55(6):394-8. [Article]
- 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. [Article]
- Song JY, Larson NR, Thati S, Torres-Vazquez I, Martinez-Rivera N, Subelzu NJ, Leon MA, Rosa-Molinar E, Schoneich C, Forrest ML, Middaugh CR, Berkland CJ: Glatiramer acetate persists at the injection site and draining lymph nodes via electrostatically-induced aggregation. J Control Release. 2019 Jan 10;293:36-47. doi: 10.1016/j.jconrel.2018.11.007. Epub 2018 Nov 7. [Article]
- Messina S, Patti F: The pharmacokinetics of glatiramer acetate for multiple sclerosis treatment. Expert Opin Drug Metab Toxicol. 2013 Oct;9(10):1349-59. doi: 10.1517/17425255.2013.811489. Epub 2013 Jun 25. [Article]
- McKeage K: Glatiramer Acetate 40 mg/mL in Relapsing-Remitting Multiple Sclerosis: A Review. CNS Drugs. 2015 May;29(5):425-32. doi: 10.1007/s40263-015-0245-z. [Article]
- Gajofatto A, Benedetti MD: Treatment strategies for multiple sclerosis: When to start, when to change, when to stop? World J Clin Cases. 2015 Jul 16;3(7):545-55. doi: 10.12998/wjcc.v3.i7.545. [Article]
- FDA Approved Drug Products: COPAXONE (glatiramer acetate), injection for subcutaneous use [Link]
- FDA Approval Package: COPAXONE (glatiramer acetate), injection for subcutaneous use [Link]
- Teva Pharmaceuticals: Glatiramer acetate SDS [Link]
- External Links
- PubChem Substance
- 46505299
- 214582
- ChEMBL
- CHEMBL1201507
- Therapeutic Targets Database
- DAP001315
- PharmGKB
- PA449760
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Glatiramer_acetate
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Prevention Multiple Sclerosis 1 4 Completed Treatment Multiple Sclerosis 4 4 Completed Treatment Multiple Sclerosis, Relapsing Forms of Multiple Sclerosis 1 4 Completed Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 4 4 Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Relapsing Multiple Sclerosis (RMS) 1 4 Recruiting Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Terminated Prevention Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Terminated Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Unknown Status Treatment Diabetic Retinopathy (DR) 1 4 Unknown Status Treatment Multiple Sclerosis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Baxter International Inc.
- Ben Venue Laboratories Inc.
- Sanofi-Aventis Inc.
- Teva Pharmaceutical Industries Ltd.
- Dosage Forms
Form Route Strength Injection, solution Parenteral Injection Subcutaneous 20 mg/1mL Injection, powder, for solution Subcutaneous 20 mg/ml Injection, solution Subcutaneous 20 mg/1mL Injection, solution Subcutaneous 40 MG/ML Injection, solution Subcutaneous 40 mg/1mL Powder, for solution Subcutaneous 20 mg / vial Solution Subcutaneous 20 mg / mL Solution Subcutaneous 40 mg / mL Injection, solution Subcutaneous Solution Subcutaneous 36 mg Injection, solution Subcutaneous 20 MG/ML Solution Subcutaneous 40 mg Injection, solution Solution Subcutaneous 20 mg Injection, solution 20 mg/ml Injection, solution 40 mg/ml - Prices
Unit description Cost Unit Copaxone 20 mg/ml Kit 20 mg Solution, 1 Box = 30 Pre-Filled Syringes 3775.25USD box Copaxone 20 mg injection kit 2264.26USD kit DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5981589 No 1999-11-09 2014-05-24 US CA2191088 No 2004-09-28 2015-05-23 Canada US8232250 No 2012-07-31 2030-08-19 US US8399413 No 2013-03-19 2030-08-19 US US8969302 No 2015-03-03 2030-08-19 US US9155776 No 2015-10-13 2030-08-19 US US9402874 No 2016-08-02 2030-08-19 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) >236°C SDS
Targets
References
- 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. [Article]
- Fridkis-Hareli M, Strominger JL: Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules. J Immunol. 1998 May 1;160(9):4386-97. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- Curator comments
- Glatiramer binds MHC class II molecule HLA-DR2 (HLA-DR15).
- General 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 cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
- Specific Function
- Mhc class ii protein complex binding
- Gene Name
- HLA-DRB1
- Uniprot ID
- P01911
- Uniprot Name
- HLA class II histocompatibility antigen, DRB1-15 beta chain
- Molecular Weight
- 29965.985 Da
References
- Fridkis-Hareli M, Strominger JL: Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules. J Immunol. 1998 May 1;160(9):4386-97. [Article]
References
- Fridkis-Hareli M, Strominger JL: Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules. J Immunol. 1998 May 1;160(9):4386-97. [Article]
Drug created at November 18, 2007 18:22 / Updated at June 30, 2022 05:13