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{{Short description|Medication}}
{{drugbox
{{Drugbox
|IUPAC_name= acetic acid; (2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid; (2S)-2-aminopentanedioic acid; (2S)-2-aminopropanoic acid; (2S)-2,6-diaminohexanoic acid
| Verifiedfields = changed
|image=Glatiramer acetate.png
| Watchedfields = changed
|CAS_number=147245-92-9
| verifiedrevid = 387696338
|ATC_prefix=L03
| image = Glatiramer acetate.svg
|ATC_suffix=AX13
| alt =
|ATC_supplemental=

|PubChem=3081884
<!--Clinical data -->
|DrugBank=APRD00999
| tradename = Copaxone,<ref name="Copaxone FDA label" /> Glatopa,<ref name="Glatopa FDA label" /> Brabio
|C=25|H=45|N=5|O=13
| Drugs.com = {{drugs.com|monograph|glatiramer_acetate}}
|molecular_weight=623.65 g/mol
| MedlinePlus = a603016
|bioavailability=
| DailyMedID = Glatiramer
|protein_bound=
| pregnancy_AU = B1
|metabolism=
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|elimination_half-life=
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| legal_CA_comment = <ref>{{cite web | title=Neurological therapies | website=] | date=9 May 2018 | url=https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/neurological-therapies.html | access-date=13 April 2024 | archive-date=4 December 2024 | archive-url=https://web.archive.org/web/20241204035952/https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/neurological-therapies.html | url-status=live }}</ref>
|legal_UK=<!-- GSL / P / POM / CD -->
| legal_UK = POM
|legal_US=<!-- OTC / Rx-only -->
| legal_UK_comment = <ref>{{cite web | title=Brabio 20 mg/mL Solution for Injection, Pre-filled Syringe - Summary of Product Characteristics (SmPC) | website=(emc) | url=https://www.medicines.org.uk/emc/product/8536/smpc | access-date=11 November 2020 | archive-date=17 November 2020 | archive-url=https://web.archive.org/web/20201117114737/https://www.medicines.org.uk/emc/product/8536/smpc | url-status=live }}</ref><ref>{{cite web | title=Copaxone 20 mg/ml solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC) | website=(emc) | date=29 September 2020 | url=https://www.medicines.org.uk/emc/product/183/smpc | access-date=11 November 2020 | archive-date=12 November 2020 | archive-url=https://web.archive.org/web/20201112194101/https://www.medicines.org.uk/emc/product/183/smpc | url-status=live }}</ref>
|legal_status=
| legal_US = Rx-only
|routes_of_administration=
| legal_US_comment = <ref name="Copaxone FDA label">{{cite web | title=Copaxone- glatiramer acetate injection, solution | website=DailyMed | date=23 July 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa88f583-4f5f-433b-80b4-1f4c9fb28357 | access-date=11 November 2020 | archive-date=31 October 2021 | archive-url=https://web.archive.org/web/20211031195926/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa88f583-4f5f-433b-80b4-1f4c9fb28357 | url-status=live }}</ref><ref name="Glatopa FDA label">{{cite web | title=Glatopa- glatiramer acetate injection, solution | website=DailyMed | date=31 July 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5f01e40a-b6f6-40fb-b37c-3d06f1428e86 | access-date=11 November 2020 | archive-date=17 November 2020 | archive-url=https://web.archive.org/web/20201117184941/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5f01e40a-b6f6-40fb-b37c-3d06f1428e86 | url-status=live }}</ref>

<!--Identifiers -->
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| CAS_number = 147245-92-9
| PubChem = 3081884
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| DrugBank = DB05259
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 5M691HL4BO
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1201507

<!-- Chemical data -->
| C=25 | H=45 | N=5 | O=13
}} }}
'''Glatiramer acetate''' (also known as '''Copolymer 1''', '''Cop-1''', or '''Copaxone''' - as marketed by ]) is an ] drug currently used to treat ]. It is a random polymer of four amino acids found in ], namely ], ], ], and ], and may work as a decoy for the immune system. Although the clinical definition of multiple sclerosis requires two or more episodes of symptoms and signs, glatiramer acetate is approved for treatment after single episodes. It is also used to treat relapsing-remitting multiple sclerosis. It is administered by ] injection.


'''Glatiramer acetate''' (also known as '''Copolymer 1''', '''Cop-1'''), sold under the brand name '''Copaxone''' among others, is an ] medication used to treat ].<ref name="Copaxone FDA label" /><ref name="Glatopa FDA label" /> Glatiramer acetate is approved in the United States to reduce the frequency of relapses, but not for reducing the progression of disability. ], but not randomized controlled trials, suggest that it may reduce progression of disability. While a conclusive ] requires a history of two or more episodes of symptoms and signs, glatiramer acetate is approved to treat a first episode anticipating a diagnosis. It is also used to treat relapsing-remitting multiple sclerosis. It is administered by ].<ref name="Copaxone FDA label" /><ref name="Glatopa FDA label" />
==Mechanism of action==
Glatiramer acetate is a random polymer (average molecular mass 6.4 kD) composed of four ] that are found in ] basic protein. The mechanism of action for glatiramer is unknown, although several have been proposed. Administration of glatiramer shifts the population of T cells from pro-inflammatory Th1 cells to regulatory Th2 cells that suppress the inflammatory response.<ref></ref> Given its resemblance to myelin basic protein, glatiramer may also act as a sort of decoy, diverting an autoimmune response against myelin. The integrity of the blood-brain barrier, however, is not appreciably affected by glatiramer, at least not in the early stages of treatment. Glatiramer acetate has been shown in clinical trials to reduce the number and severity of exacerbations.<ref></ref>


It is a mixture of random-sized peptides that are composed of the four ] found in ], namely ], ], ], and ]. Myelin basic protein is the ] in the ] of the neurons that stimulates an ] reaction in people with MS, so the peptide may work as a decoy for the attacking immune cells.
The mechanism(s) by which glatiramer acetate exerts its effects in patients with Multiple Sclerosis (MS) is (are) not fully elucidated. However, it is thought to act by modifying immune processes that are currently believed to be responsible for the pathogenesis of MS. This hypothesis is supported by findings of studies that have been carried out to explore the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a condition induced in several animal species through immunization against central nervous system derived material containing myelin and often used as an experimental animal model of MS. 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. <ref></ref>


It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref>
==Development==
Glatiramer acetate was originally discovered by Professor ], Professor ], and Dr. ] at the ] in ]. The efficacy and safety of glatiramer acetate were demonstrated in three main clinical trials. The first trial, led by Professor ], was performed in a single center, double-blind, ] and included 50 patients.{{Citation needed|date=February 2010}}
The second trial was a 2-year, multi-center, randomized, double-blind, placebo controlled trial and was performed in eleven ] centers involving 251 patients. This study was led by Professor Kenneth Johnson, Chairman of the Department of Neurology, ], ].{{Citation needed|date=February 2010}} The third trial, a double-blind, multi-center, multi-country ] study, involved 29 MS Centers in six European countries and ], with the participation of 239 patients. This study was led by Professor G. Comi, Department of Neuroscience, ], the ].{{Citation needed|date=February 2010}}


== History ==
==Marketing and distribution==
Glatiramer acetate was originally discovered at the ]. Three main clinical trials followed to demonstrate safety and efficacy: The first trial was performed in a single center, double-blind, ] and included 50 patients.<ref>{{cite journal | vauthors = Bornstein MB, Miller A, Slagle S, Weitzman M, Crystal H, Drexler E, Keilson M, Merriam A, Wassertheil-Smoller S, Spada V | title = A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis | journal = The New England Journal of Medicine | volume = 317 | issue = 7 | pages = 408–14 | date = August 1987 | pmid = 3302705 | doi = 10.1056/NEJM198708133170703 }}</ref>
Glatiramer acetate has been approved for marketing in 47 countries worldwide, including the ], ], ], 22 ] Countries including the new accessors, ], ], ], ], ] and ].
The second trial was a two-year, multi-center, randomized, double-blind, placebo controlled trial and involved 251 patients.<ref>{{cite journal | vauthors = Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB | title = Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group | journal = Neurology | volume = 45 | issue = 7 | pages = 1268–76 | date = July 1995 | pmid = 7617181 | doi = 10.1212/WNL.45.7.1268 | s2cid = 28895177 }}</ref> The third trial was a double-blind ] study involving participation of 239 patients.<ref>{{cite journal | vauthors = Comi G, Filippi M, Wolinsky JS | title = European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging--measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group | journal = Annals of Neurology | volume = 49 | issue = 3 | pages = 290–7 | date = March 2001 | pmid = 11261502 | doi = 10.1002/ana.64 | s2cid = 35614752 }}</ref>


== Medical uses ==
Approval in the US was obtained in 1996. Glatiramer acetate was approved for marketing in the ] in August ], and launched in December. This first approval in a major European market enabled Teva to file for approval all over the ] under the mutual recognition procedure.
Glatiramer acetate is ] for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.<ref name="Copaxone FDA label" />


A 2010 ] review concluded that glatiramer acetate had partial efficacy in "relapse-related clinical outcomes" but no effect on progression of the disease.<ref name="2010cochrane">{{cite journal | vauthors = La Mantia L, Munari LM, Lovati R | title = Glatiramer acetate for multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 5 | issue = 5 | pages = CD004678 | date = May 2010 | pmid = 20464733 | doi = 10.1002/14651858.CD004678.pub2 }}</ref> As a result, it is approved by the FDA for reducing the frequency of relapses, but not for reducing the progression of disability.<ref name="Copaxone FDA label" /><ref name="Glatopa FDA label" />
==Side effects==
]
Side effects can include a lump at the injection site (injection site reaction) in approximately 30%<ref>iGuard.org TSQM survey results (n=1700+): http://www.iguard.org/medication/copaxone</ref> of users, and aches, fever, chills (flu-like symptoms) in 10% of users. (?) Copaxone is the only disease modifying drug that does not cause flu like symptoms in patients. Side effect symptoms are generally mild in nature. A reaction that involves flushing, shortness in breath, anxiety & rapid heartbeat has been reported soon after injection in up to 5% of patients (usually after injecting directly into a vein). These side effects subside within thirty minutes. Over time, a visible dent at the injection site can occur due to the local destruction of fat tissue, known as ], that may develop.


A 15-year followup of the original trial compared patients who continued with glatiramer to patients who dropped out of the trial. Patients with glatiramer had reduced relapse rates, and decreased disability progression and transition to secondary progressive MS, compared to patients who did not continue glatiramer. However, the two groups were not necessarily comparable, as it was no longer a randomized trial. There were no long-term safety issues.<ref name="Ford2010">{{cite journal | vauthors = Ford C, Goodman AD, Johnson K, Kachuck N, Lindsey JW, Lisak R, Luzzio C, Myers L, Panitch H, Preiningerova J, Pruitt A, Rose J, Rus H, Wolinsky J | display-authors = 6 | title = Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate | journal = Multiple Sclerosis | volume = 16 | issue = 3 | pages = 342–50 | date = March 2010 | pmid = 20106943 | pmc = 2850588 | doi = 10.1177/1352458509358088 | doi-access = free }}</ref>
More serious side effects have been reported for glatiramer acetate, according to the FDA's prescribing label, these include serious side effects to the body's Cardiovascular System, Digestive System (including Liver),
Hemic and Lymphatic System, Musculoskeletal System, Nervous System, Respiratory System, Special Senses (in particular the eyes), Urogenital System; also reported have been Metabolic and Nutritional Disorders; however a link between glatiramer acetate and these adverse effects has not been definitively established.<ref>FDA Copaxone Label: http://www.fda.gov/cder/foi/label/2001/20622s15lbl.pdf</ref>


== Adverse effects ==
==Effectiveness==
]
Evidence supporting the effectiveness of glatiramer acetate in decreasing the frequency of relapses in patients with Relapsing-Remitting Multiple Sclerosis (RR MS) derives from two placebo-controlled trials, both of which used a glatiramer acetate dose of 20 mg/day. (No other
dose or dosing regimen has been studied in placebo-controlled trials of RR MS).<ref>http://www.copaxone.com/pdf/PrescribingInformation.pdf</ref> A comparative trial of the approved 20 mg dose and the 40 mg dose showed no significant difference in efficacy between these doses<ref>the 9006 trial; Cohen JA et al. Neurology. 2007;68:939-944)</ref>.


Side effects may include a lump at the injection site (]) in approximately 30% of users, and aches, fever, chills (flu-like symptoms) in approximately 10% of users.<ref>{{cite web | url = https://www.mediguard.org/medication/view/copaxone | title = Copaxone | publisher = MediGuard | access-date = 2018-02-03 | archive-date = 2018-02-03 | archive-url = https://web.archive.org/web/20180203181436/https://www.mediguard.org/medication/view/copaxone | url-status = live }}</ref> Side effect symptoms are generally mild in nature. A reaction that involves flushing, shortness of breath, anxiety and rapid heartbeat has been reported soon after injection in up to 5% of patients (usually after inadvertently injecting directly into a vein). These side effects subside within thirty minutes. Over time, a visible dent at a repeat-injection site can occur due to the local destruction of fat tissue, known as ], that may develop.
In its pivotal trial <ref>FDA marketing label - http://www.copaxone.com/pdf/PrescribingInformation.pdf</ref> of 251 patients, after 2 years Copaxone failed to show any advantage in halting disability progression (78% of treated patients were Progression-free versus 75% Progression-free on placebo).


More serious side effects have been reported for glatiramer acetate, according to the FDA's prescribing label, these include serious side effects to the cardiovascular, digestive (including the liver), hematopoietic, lymphatic, musculoskeletal, nervous, respiratory, and urogenital systems as well as special senses (in particular the eyes). Metabolic and nutritional disorders have also been reported; however a link between glatiramer acetate and these adverse effects has not been established.<ref name="Copaxone FDA label" /><ref name="Glatopa FDA label" />
A 2004 Cochrane Medical review<ref>Cochrane Medical review of Copaxone - http://www.cochrane.org/reviews/en/ab004678.html</ref> pointed out that "''Glatiramer acetate did not show any beneficial effect on the main outcome measures in MS, i.e. disease progression, and it does not substantially affect the risk of clinical relapses''."


It may also cause ].<ref>{{cite book | vauthors = Krafchik BR | veditors = Schachner LA, Hansen RC | title = Pediatric Dermatology | chapter = Reaction Patterns | date = 2011 | publisher = Elsevier Health Sciences | isbn = 978-0-7234-3665-2 | page = 1022 | chapter-url = https://books.google.com/books?id=tAlGLYplkacC&pg=PA1022 }}</ref>
As a result<ref>Copaxone marketing materials - http://www.copaxone.com/NewlyDiagnosed/pivotTrial.aspx</ref>, the FDA marketing label for Copaxone does not as yet have an indication for reducing the progression of disability.


== Mechanism of action ==
On February 25, 2010, a long-term study on Copaxone was published in the February issue of the journal Multiple Sclerosis. It was the longest prospective and continuous evaluation ever conducted in relapsing-remitting multiple sclerosis. The fifteen-year clinical study showed that more than 80 percent of patients were still walking without assistance, despite a mean MS disease duration of 22 years, and two-thirds of the patients have not as yet transitioned to secondary progressive MS. Patients who remained in the study over 15 years showed a reduction in relapse rate from baseline, as well as minimal increase on the Expanded Disability Status Scale (EDSS.) It also established the long-term safety profile associated with Copaxone. <ref>The study “Continuous Long-Term Immunomodulatory Therapy in Relapsing Multiple Sclerosis: Results from the 15-Year Analysis of the U.S. Prospective Open-label Study of Glatiramer Acetate,” a follow-up to the pivotal, Phase III trial, followed 100 ongoing Copaxone® (glatiramer acetate injection) patients starting in 1991. Patients' EDSS scores were evaluated every six months. Confirmed disability progression was defined as ‰¥1.0 EDSS point increase sustained for six months. Patients were classified as “stable/improved” if EDSS score changes were less or equal to 0.5 points. Proportions of patients who reached confirmed thresholds of EDSS 4, 6, or 8 while on Copaxone®, and Kaplan-Meier (KM) estimates of median times to these thresholds, were obtained. http://www.mscare.org/cmsc/Informs-Copaxone-Demonstrates-Robust-Long-Term-Efficacy-and-Safety.html</ref>
Glatiramer acetate is a random polymer (average molecular mass {{val|6.4|ul=kDa}}) composed of four ] found in ]. The mechanism of action for glatiramer acetate is not fully elucidated. It is thought to act by modifying immune processes that are believed to be responsible for the pathogenesis of MS. Administration of glatiramer acetate shifts the population of T cells from proinflammatory ] to regulatory ] that suppress the inflammatory response.<ref>{{cite journal | vauthors = Arnon R, Sela M | url = http://www.weizmann.ac.il/ICS/booklet/1/pdf/copaxon.pdf | archive-url = https://web.archive.org/web/20030907080548/http://www.weizmann.ac.il/ICS/booklet/1/pdf/copaxon.pdf | url-status = dead | archive-date = 2003-09-07 | title = The chemistry of the Copaxone drug | pages = 12–17 | journal = Chem. Israel | year = 1999 | volume = 1 }}</ref> This is done by the inhibition of secretion of proinflammatory cytokines (IL-1, IL-12, TNF, INFγ) by Th1 T-cells, thereby inducing Th2 T-cells to cross the blood–brain barrier and produce anti-inflammatory cytokines (IL-4, IL-5, IL-13, IL-10, TGF-β).<ref>https://go.drugbank.com/drugs/DB05259 {{Webarchive|url=https://web.archive.org/web/20221130103008/https://go.drugbank.com/drugs/DB05259 |date=2022-11-30 }}; Glatiramer Mechanism of Action</ref> Given its resemblance to myelin basic protein, glatiramer acetate may act as a decoy, diverting an autoimmune response against myelin. This hypothesis is supported by findings of studies that have been carried out to explore the pathogenesis of ] (EAE), a condition induced in several animal species through immunization against central nervous system derived material containing myelin and often used as an experimental animal model of MS. Studies in animals and in vitro systems suggest that upon its administration, glatiramer acetate-specific ] (Tregs) are induced and activated in the periphery, inhibiting the inflammatory reaction to myelin basic protein.<ref name="Copaxone FDA label" /><ref name="Glatopa FDA label" />


The integrity of the ], however, is not appreciably affected by glatiramer acetate, at least not in the early stages of treatment. Glatiramer acetate has been shown in clinical trials to reduce the number and severity of multiple sclerosis exacerbations.<ref>{{cite web | url = http://www.mult-sclerosis.org/Copaxone.html | title = Copaxone | work = All About Multiple Sclerosis | access-date = 2007-07-16 | archive-date = 2020-11-14 | archive-url = https://web.archive.org/web/20201114003056/http://www.mult-sclerosis.org/Copaxone.html | url-status = live }}</ref>
In 2 recent studies, both reported at the 2007 ECTRIMS meeting, the efficacy of glatiramer acetate was compared to high-dose/high-frequency interferon beta. In the REGARD study, Rebif was compared to glatiramer, and in the BEYOND study, Betaseron was compared to glatiramer. In both trials, there was no significant difference between interferon and glatiramer in the primary endpoints (time to relapse) or in any clinical endpoints, although some differences in MRI measures of disease activity have been claimed.


== Society and culture ==
A recent study by the Department of Neurology at The University of Texas Health Science Center argues that a double-blind three year study failed to demonstrate a treatment effect of Glatiramer acetate on Primary-Progressive Multiple Sclerosis.<ref>{{cite journal |author=Wolinsky J, Narayana P, O'Connor P et al. |title=Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial |journal=Ann Neurol |volume=61 |issue=1 |pages=14&ndash;24 |year=2007 |pmid=17262850 |doi=10.1002/ana.21079}}</ref>
=== Marketing ===
Glatiramer acetate has been approved for marketing in numerous countries worldwide, including the ], ], ] and 24 ] countries.<ref>{{cite journal | vauthors = McKeage K | title = Glatiramer Acetate 40 mg/mL in Relapsing-Remitting Multiple Sclerosis: A Review | journal = CNS Drugs | volume = 29 | issue = 5 | pages = 425–32 | date = May 2015 | pmid = 25906331 | doi = 10.1007/s40263-015-0245-z | s2cid = 30186027 }}</ref><ref>{{cite journal | vauthors = Comi G, Amato MP, Bertolotto A, Centonze D, De Stefano N, Farina C, Gallo P, Ghezzi A, Grimaldi LM, Mancardi G, Marrosu MG, Montanari E, Patti F, Pozzilli C, Provinciali L, Salvetti M, Tedeschi G, Trojano M | display-authors = 6 |title=The heritage of glatiramer acetate and its use in multiple sclerosis|journal=Multiple Sclerosis and Demyelinating Disorders|date=2016|volume=1|issue=1|doi=10.1186/s40893-016-0010-2|doi-access=free}}</ref> Approval in the U.S. was obtained in 1997.<ref>{{cite web|url=http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/211/copaxone|work=CenterWatch|title=Copaxone|access-date=2017-02-01|archive-date=2019-08-05|archive-url=https://web.archive.org/web/20190805014203/https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/211/copaxone|url-status=dead}}</ref> Glatiramer acetate was approved for marketing in the ] in August 2000, and launched in December.<ref>{{cite web|url=http://www.thepharmaletter.com/article/teva-s-copaxone-approved-in-uk|title=Teva's Copaxone approved in UK|work=The Pharma Letter|access-date=2017-02-01|archive-date=2021-10-31|archive-url=https://web.archive.org/web/20211031195927/https://www.thepharmaletter.com/article/teva-s-copaxone-approved-in-uk|url-status=live}}</ref> This first approval in a major European market led to approval across the ] under the ].
Iran is proceeding with domestic manufacture of glatiramer acetate.<ref>{{cite web | url = http://tofighdaru.ir/en/products-2/glatiramer-acetate/ | publisher = Tofigh Daru Research and Engineering Company | title = Glatiramer Acetate | access-date = 2017-02-01 | archive-date = 2018-10-21 | archive-url = https://web.archive.org/web/20181021221746/http://tofighdaru.ir/en/products-2/glatiramer-acetate/ | url-status = dead }}</ref><ref>{{cite web | url = http://en.trend.az/iran/2020693.html | title = Iran to manufacture multiple sclerosis cure | work = Trend News Agency | date = 1 May 2012 | vauthors = Isayev S, Jafarov T | access-date = 1 February 2017 | archive-date = 1 December 2017 | archive-url = https://web.archive.org/web/20171201131913/https://en.trend.az/iran/2020693.html | url-status = live }}</ref>


=== Patent status ===
In February, 2009, the FDA approved an expanded indication for Copaxone "for reduction of the frequency of relapses in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), including patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis." <ref> http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020622s057lbl.pdf </ref>


] subsidiary Sandoz has marketed Glatopa since 2015, a generic version of the original Teva 20&nbsp;mg formulation that requires daily injection.<ref>{{cite web | url = https://www.novartis.com/news/media-releases/sandoz-announces-us-launch-glatopatm-first-generic-competitor-copaxone%C2%AE-20mg | title = Sandoz announces US launch of Glatopa | year = 2015 | publisher = Novartis | access-date = 2017-02-21 | archive-date = 2018-02-03 | archive-url = https://web.archive.org/web/20180203181521/https://www.novartis.com/news/media-releases/sandoz-announces-us-launch-glatopatm-first-generic-competitor-copaxone%C2%AE-20mg | url-status = dead }}</ref>
The expansion of Copaxone's indication to include patients with a Clinically Isolated Syndrome (CIS) is based on a clinical trial (PreCISe) which showed that Copaxone delayed the progression from the first clinical event to Clinically Definite Multiple Sclerosis (CDMS) in a statistically significant and clinically meaningful manner, corresponding to a risk reduction of 45%. The proportion of patients who converted to CDMS was 43% for the placebo group and 25% in the Copaxone group. <ref>http://www.medicalnewstoday.com/articles/90768.php</ref>


Teva developed a long-acting 40&nbsp;mg formulation, marketed since 2015, which reduced required injections to three per week.<ref>{{cite web | url = https://multiplesclerosisnewstoday.com/2015/10/09/new-3-times-per-week-regimen-tevas-copaxone-safe-effective-increases-patient-compliance-ectrims2015/ | title = New 3-Times-Per-Week Regimen For Teva's Copaxone | work = Multiple Sclerosis News Today | date = 9 October 2015 | vauthors = Silva P | access-date = 22 February 2017 | archive-date = 24 February 2019 | archive-url = https://web.archive.org/web/20190224103151/https://multiplesclerosisnewstoday.com/2015/10/09/new-3-times-per-week-regimen-tevas-copaxone-safe-effective-increases-patient-compliance-ectrims2015/ | url-status = live }}</ref> In October 2017, the FDA approved a generic version, which is manufactured in India by ], and imported and sold by Dutch firm ].<ref>{{cite news | vauthors = Erman M, Grover D | url = https://www.reuters.com/article/us-mylan-nl-stocks-teva-pharm-ind/mylan-surges-teva-slumps-after-fda-okays-copaxone-copy-idUSKCN1C91CT | title = Mylan surges, Teva slumps after FDA okays Copaxone copy | newspaper = Reuters | date = 3 October 2017 | access-date = 4 October 2017 | archive-date = 4 October 2017 | archive-url = https://web.archive.org/web/20171004152527/http://www.reuters.com/article/us-mylan-nl-stocks-teva-pharm-ind/mylan-surges-teva-slumps-after-fda-okays-copaxone-copy-idUSKCN1C91CT | url-status = live }}</ref><ref>{{cite web|url=http://www.natcopharma.co.in/about/news|title=NATCO's marketing partner Mylan receives final approval of generic glatiramer acetate, for both 20 mg/mL and 40 mg/mL versions|website=NATCO Pharma (India)|date=3 October 2017|access-date=4 October 2017|archive-date=10 January 2019|archive-url=https://web.archive.org/web/20190110005909/http://www.natcopharma.co.in/about/news/|url-status=dead}}></ref> In February 2018, Sandoz received FDA approval for their generic version.<ref>{{cite web|url=https://www.novartis.com/news/media-releases/sandoz-announces-us-fda-approval-and-launch-glatopar-40-mgml-three-times-week-generic-option-relapsing-forms-multiple-sclerosis|title=Sandoz announces US FDA approval and launch of Glatopa 40 mg/mL|website=Novartis International AG|date=February 13, 2018|access-date=May 10, 2018|archive-date=May 11, 2018|archive-url=https://web.archive.org/web/20180511154819/https://www.novartis.com/news/media-releases/sandoz-announces-us-fda-approval-and-launch-glatopar-40-mgml-three-times-week-generic-option-relapsing-forms-multiple-sclerosis|url-status=live}}</ref> In parallel with the development and approval processes, the generic competitors have disputed Teva's newer patents, any of which if upheld, would prevent marketing of long-acting generics.<ref>{{cite web|url=http://www.biopharmadive.com/news/tevas-copaxone-still-growing-despite-patent-risks/423956/|title=Teva's Copaxone still growing despite patent risks|work=BioPharmaDive|access-date=2017-02-22|archive-date=2018-12-01|archive-url=https://web.archive.org/web/20181201005332/https://www.biopharmadive.com/news/tevas-copaxone-still-growing-despite-patent-risks/423956/|url-status=live}}</ref>
==Research==
Glatiramer has been found to be protective in a mouse model of cerebral ].<ref name="Lackner2009">Lackner P., Part A., Burger C., Dietmann A., Broessner G., Helbok R., Reindl M., Schmutzhard E., Beer R. (2009) Glatiramer acetate reduces the risk for experimental cerebral malaria: a pilot study. Malar J. 27;8(1):36</ref>


While the ] on the chemical drug expired in 2015,<ref>{{cite web | vauthors = Helfand C | url = http://www.fiercepharma.com/special-report/copaxone | title = Copaxone | work = FiercePharma | access-date = 2017-01-31 | archive-date = 2020-08-09 | archive-url = https://web.archive.org/web/20200809094529/https://www.fiercepharma.com/special-report/copaxone | url-status = live }}</ref> Teva obtained new US patents covering pharmaceutical formulations for long-acting delivery.<ref>{{cite web | vauthors = Decker S | date = 1 September 2016 | url = https://www.bloomberg.com/news/articles/2016-09-01/teva-loses-decision-on-validity-of-302-copaxone-patent | title = Teva loses decision on validity of 302 copaxone patent | work = Bloomberg Markets | access-date = 2017-01-31 | archive-date = 2019-07-09 | archive-url = https://web.archive.org/web/20190709052331/https://www.bloomberg.com/news/articles/2016-09-01/teva-loses-decision-on-validity-of-302-copaxone-patent | url-status = live }}</ref> Litigation from industry competitors in 2016-2017 resulted in the new patents being judged invalid.<ref>{{cite web | vauthors = Decker S, Flanagan C, Benmeleh Y | date = 30 January 2017 | url = https://www.bloomberg.com/news/articles/2017-01-30/teva-loses-ruling-invalidating-patents-on-copaxone-drug | title = Teva loses ruling invalidating patents on copaxone drug | work = Bloomberg Markets | access-date = 2017-01-31 | archive-date = 2021-09-23 | archive-url = https://web.archive.org/web/20210923033120/https://www.bloomberg.com/news/articles/2017-01-30/teva-loses-ruling-invalidating-patents-on-copaxone-drug | url-status = live }}</ref><ref>{{Cite news|url=https://www.newspapers.com/clip/21233509/in_the_region/|title=Teva loses patent ruling|last=<!-- no byline -->|date=September 2, 2017|work=The Philadelphia Inquirer|access-date=June 23, 2018|agency=Bloomberg News|department=Briefcase|page=A12|via=Newspapers.com (Publisher Extra)|archive-date=June 24, 2018|archive-url=https://web.archive.org/web/20180624063939/https://www.newspapers.com/clip/21233509/in_the_region/|url-status=live}}</ref> In October 2018, the ] for the ] upheld the patent invalidation for ].<ref>{{cite news|url=https://www.reuters.com/article/teva-mylan-patent/update-1-us-appeals-court-upholds-ruling-that-canceled-teva-copaxone-patents-idUSL2N1WS0PB|newspaper=Reuters|title=U.S. appeals court upholds ruling that canceled Teva Copaxone patents|date=October 12, 2018|access-date=October 12, 2018|archive-date=October 12, 2018|archive-url=https://web.archive.org/web/20181012214540/https://www.reuters.com/article/teva-mylan-patent/update-1-us-appeals-court-upholds-ruling-that-canceled-teva-copaxone-patents-idUSL2N1WS0PB|url-status=live}}</ref><ref>{{cite web|url=http://www.cafc.uscourts.gov/sites/default/files/opinions-orders/17-1575.Opinion.10-12-2018.pdf|website=United States Court of Appeals for the Federal Circuit|title=In Re: Copaxone Consolidated Cases|date=October 12, 2018|access-date=October 12, 2018|archive-date=December 22, 2018|archive-url=https://web.archive.org/web/20181222153723/http://www.cafc.uscourts.gov/sites/default/files/opinions-orders/17-1575.Opinion.10-12-2018.pdf|url-status=live}}</ref> The case reflects the larger controversy over ] of branded drugs. On October 31, 2024, the ] fined Teva €462.6 million «over misuse of the patent system and disparagement to delay rival multiple sclerosis medicine», having attempted to obstacle other producers of glatiramer acetate both by abusing the patent system and by setting up a misinformation campaign targeting other glatiramer producers.<ref name="eucommission2024">{{cite web |title=Commission fines Teva €462.6 million over misuse of the patent system and disparagement to delay rival multiple sclerosis medicine |url=https://ec.europa.eu/commission/presscorner/detail/en/ip_24_5581 |website=European Commission |access-date=31 October 2024 |archive-date=5 November 2024 |archive-url=https://web.archive.org/web/20241105144824/https://ec.europa.eu/commission/presscorner/detail/en/ip_24_5581 |url-status=live }}</ref>
Glatiramer is currently in Phase I clinical trials for Dry Age-Related Macular Degeneration (AMD).


==References== == References ==
{{reflist|2}} {{reflist}}


{{Multiple sclerosis}} {{Multiple sclerosis}}
{{Immunostimulants}} {{Immunostimulants}}
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