Glatiramer acetate

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Glatiramer acetate
Clinical data
Trade namesCopaxone,[1] Glatopa,[2] Brabio
AHFS/Drugs.comMonograph
MedlinePlusa603016
License data
Pregnancy
category
  • AU: B1
Subcutaneous injection
ATC code
Legal status
Legal status
Identifiers
ECHA InfoCard
100.248.824 Edit this at Wikidata
Chemical and physical data
FormulaC25H45N5O13
Molar mass623.657 g·mol−1
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Glatiramer acetate (also known as Copolymer 1, Cop-1), sold under the brand name Copaxone among others, is an

subcutaneous injection.[1][2]

It is a mixture of random-sized peptides that are composed of the four

autoimmune
reaction in people with MS, so the peptide may work as a decoy for the attacking immune cells.

It is on the World Health Organization's List of Essential Medicines.[6]

History

Glatiramer acetate was originally discovered at the

placebo controlled trial and included 50 patients.[7]
The second trial was a two-year, multi-center, randomized, double-blind, placebo controlled trial and involved 251 patients.
MRI study involving participation of 239 patients.[9]

Medical uses

Glatiramer acetate is indicated 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.[1]

A 2010 Cochrane review concluded that glatiramer acetate had partial efficacy in "relapse-related clinical outcomes" but no effect on progression of the disease.[10] As a result, it is approved by the FDA for reducing the frequency of relapses, but not for reducing the progression of disability.[1][2]

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.[11]

Adverse effects

An injection site reaction on the upper left arm

Side effects may include a lump at the injection site (injection site reaction) in approximately 30% of users, and aches, fever, chills (flu-like symptoms) in approximately 10% of users.[12] 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 lipoatrophy, that may develop.

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.[1][2]

It may also cause

Jessner lymphocytic infiltrate.[13]

Mechanism of action

Glatiramer acetate is a random polymer (average molecular mass 6.4 

regulatory T cells (Tregs) are induced and activated in the periphery, inhibiting the inflammatory reaction to myelin basic protein.[1][2]

The integrity of the blood–brain barrier, 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.[16]

Society and culture

Marketing

Glatiramer acetate has been approved for marketing in numerous countries worldwide, including the

U.K. in August 2000, and launched in December.[20] This first approval in a major European market led to approval across the European Union under the mutual recognition procedure
. Iran is proceeding with domestic manufacture of glatiramer acetate.[21][22]

Patent status

Novartis subsidiary Sandoz has marketed Glatopa since 2015, a generic version of the original Teva 20 mg formulation that requires daily injection.[23]

Teva developed a long-acting 40 mg formulation, marketed since 2015, which reduced required injections to three per week.[24] In October 2017, the FDA approved a generic version, which is manufactured in India by Natco Pharma, and imported and sold by Dutch firm Mylan.[25][26] In February 2018, Sandoz received FDA approval for their generic version.[27] 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.[28]

While the

Federal Circuit upheld the patent invalidation for obviousness.[33][34] The case reflects the larger controversy over evergreening
of generic drugs.

References

  1. ^ a b c d e f g h "Copaxone- glatiramer acetate injection, solution". DailyMed. 23 July 2020. Retrieved 11 November 2020.
  2. ^ a b c d e f g "Glatopa- glatiramer acetate injection, solution". DailyMed. 31 July 2020. Retrieved 11 November 2020.
  3. ^ "Neurological therapies". Health Canada. 9 May 2018. Retrieved 13 April 2024.
  4. ^ "Brabio 20 mg/mL Solution for Injection, Pre-filled Syringe - Summary of Product Characteristics (SmPC)". (emc). Retrieved 11 November 2020.
  5. ^ "Copaxone 20 mg/ml solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC)". (emc). 29 September 2020. Retrieved 11 November 2020.
  6. hdl:10665/371090
    . WHO/MHP/HPS/EML/2023.02.
  7. PMID 3302705
    .
  8. S2CID 28895177
    .
  9. S2CID 35614752
    .
  10. PMID 20464733
    .
  11. PMID 20106943
    .
  12. ^ "Copaxone". MediGuard.
  13. ISBN 978-0-7234-3665-2
    .
  14. ^ Arnon R, Sela M (1999). "The chemistry of the Copaxone drug" (PDF). Chem. Israel. 1: 12–17. Archived from the original (PDF) on 2003-09-07.
  15. ^ https://go.drugbank.com/drugs/DB05259; Glatiramer Mechanism of Action
  16. ^ "Copaxone". All About Multiple Sclerosis.
  17. S2CID 30186027
    .
  18. doi:10.1186/s40893-016-0010-2
    .
  19. ^ "Copaxone". CenterWatch.
  20. ^ "Teva's Copaxone approved in UK". The Pharma Letter.
  21. ^ "Glatiramer Acetate". Tofigh Daru Research and Engineering Company. Archived from the original on 2018-10-21. Retrieved 2017-02-01.
  22. ^ Isayev S, Jafarov T (1 May 2012). "Iran to manufacture multiple sclerosis cure". Trend News Agency.
  23. ^ "Sandoz announces US launch of Glatopa". Novartis. 2015. Archived from the original on 2018-02-03. Retrieved 2017-02-21.
  24. ^ Silva P (9 October 2015). "New 3-Times-Per-Week Regimen For Teva's Copaxone". Multiple Sclerosis News Today.
  25. ^ Erman M, Grover D (3 October 2017). "Mylan surges, Teva slumps after FDA okays Copaxone copy". Reuters. Retrieved 4 October 2017.
  26. ^ "NATCO's marketing partner Mylan receives final approval of generic glatiramer acetate, for both 20 mg/mL and 40 mg/mL versions". NATCO Pharma (India). 3 October 2017. Archived from the original on 10 January 2019. Retrieved 4 October 2017.>
  27. ^ "Sandoz announces US FDA approval and launch of Glatopa 40 mg/mL". Novartis International AG. February 13, 2018. Retrieved May 10, 2018.
  28. ^ "Teva's Copaxone still growing despite patent risks". BioPharmaDive.
  29. ^ Helfand C. "Copaxone". FiercePharma.
  30. ^ Decker S (1 September 2016). "Teva loses decision on validity of 302 copaxone patent". Bloomberg Markets.
  31. ^ Decker S, Flanagan C, Benmeleh Y (30 January 2017). "Teva loses ruling invalidating patents on copaxone drug". Bloomberg Markets.
  32. ^ "Teva loses patent ruling". Briefcase. The Philadelphia Inquirer. Bloomberg News. September 2, 2017. p. A12. Retrieved June 23, 2018 – via Newspapers.com (Publisher Extra).
  33. ^ "U.S. appeals court upholds ruling that canceled Teva Copaxone patents". Reuters. October 12, 2018. Retrieved October 12, 2018.
  34. ^ "In Re: Copaxone Consolidated Cases" (PDF). United States Court of Appeals for the Federal Circuit. October 12, 2018. Retrieved October 12, 2018.
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