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Glatiramer acetate
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| Systematic (IUPAC) name | |
| Glatiramer acetate | |
| Identifiers | |
| CAS number | |
| ATC code | L03 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | ? |
| Mol. mass | ? |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
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| Legal status | |
| Routes | ? |
Glatiramer Acetate is the generic name for the drug Copaxone or Copolymer 1, developed by Teva Pharmaceuticals. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction In Pharmacology and Toxicology, a route A drug, broadly speaking is any chemical substance that when absorbed into the body Teva Pharmaceutical Industries Ltd (טבע תעשיות פרמצבטיות בע"מ is an international Pharmaceutical company headquartered in Petah Tikva It is an immunomodulator, licensed in much of the world for reduced frequency of relapses in relapsing-remitting multiple sclerosis. An immunomodulator is a drug used for its effect on the Immune system. Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the Copaxone is administered by subcutaneous injection at a dose of 20 mg per day. The subcutaneous tissue or subcutis is the layer of Loose connective tissue directly underlying the Dermis. It is a non-interferon and non steroidal medication. Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents A steroid is a Terpenoid Lipid characterized by a Carbon skeleton with four fused rings generally arranged in a 6-6-6-5 fashion
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How Glatiramer Acetate Works
Glatiramer acetate is a random polymer (average molecular mass 6. 4 kD) composed of four amino acids that are found in myelin basic protein. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Myelin is an electrically-insulating Dielectric Phospholipid layer that surrounds only the Axons of many Neurons It is an outgrowth 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. [1] 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. [2]
Development
Glatiramer acetate was originally discovered by Professor Sela, Professor Arnon and Dr. Teitelbaum at the Weizmann Institute of Science in Israel. The Weizmann Institute of Science (מכון ויצמן למדע known as Machon Weizmann is a university and research institute in Rehovot, Israel. For a topic outline on this subject see List of basic Israel topics. The efficacy and safety of glatiramer acetate were demonstrated in three main clinical trials: The first trial, led by Professor M. Bornstein, was performed in a single center, double-blind, placebo controlled trial and included 50 patients. The second trial was a 2-year, multi-center, randomized, double-blind, placebo controlled trial and was performed in eleven US centers involving 251 patients. The United States of America —commonly referred to as the This study was led by Professor Kenneth Johnson, Chairman of the Department of Neurology, University of Maryland Medical Center, Baltimore. University of Maryland may refer to University of Maryland College Park, a research-extensive and flagship university when the term "University of Maryland" The third trial, a double-blind, multi-center, multi-country MRI study, involved 29 MS Centers in six European countries and Canada, with the participation of 239 patients. Country to "Dominion of Canada" or "Canadian Federation" or anything else please read the Talk Page This study was led by Professor G. Comi, Department of Neuroscience, San Raffaele Hospital, the University of Milan. The San Raffaele Hospital ( HSR) is a University hospital situated in Milan, Italy. The University of Milan (Università degli Studi di Milano UNIMI is one the largest universities in Italy, with about 62801 Students a teaching and research
Marketing and distribution
Glatiramer acetate has been approved for marketing in 47 countries worldwide, including the United States, Israel, Canada, 22 European Union Countries including the new accessors, Switzerland, Australia, Russia, Brazil, Argentina and Czech republic. The United States of America —commonly referred to as the For a topic outline on this subject see List of basic Israel topics. Country to "Dominion of Canada" or "Canadian Federation" or anything else please read the Talk Page The European Union ( EU) is a political and economic union of twenty-seven member states, located primarily in Switzerland (English pronunciation; Schweiz Swiss German: Schwyz or Schwiiz Suisse Svizzera Svizra officially the Swiss Confederation For a topic outline on this subject see List of basic Australia topics. Russia (Россия Rossiya) or the Russian Federation ( Rossiyskaya Federatsiya) is a transcontinental Country extending |utc_offset = -2 to -4 |time_zone_DST = BRST |utc_offset_DST = -2 to -5 |cctld For a topic outline on this subject see List of basic Argentina topics. The Czech Republic ( ˈt͡ʃɛskaː ˈrɛpuˌblɪka short form in Česko ˈt͡ʃɛskɔ also called Czechia,
Approval in the US was obtained in 1996. Glatiramer acetate was approved for marketing in the U.K. in August 2000, and launched in December. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located 2000 ( MM) was a Leap year that started on Saturday of the Common Era, in accordance with the Gregorian calendar. This first approval in a major European market enabled Teva to file for approval all over the European Union under the mutual recognition procedure. The European Union ( EU) is a political and economic union of twenty-seven member states, located primarily in
Side Effects
Side effects generally include a lump at the injection site (injection site reaction), aches, fever, chills and are generally mild in nature. Occasionally a reaction occurs minutes after injection in which there is flushing, shortness in breath, anxiety & rapid heartbeat. These side effects subside within thirty minutes. Over time, a visible dent at the injection site due to the local destruction of fat tissue, known as lipoatrophy, may develop. Lipoatrophy is the term describing the localized loss of fat tissue
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. [1]
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). [2] A comparative trial of the approved 20 mg dose and the 40 mg dose showed no significant difference in efficacy between these doses[3].
However, a 2004 Cochrane Medical review[4] 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. "
In its pivotal trial [5] 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).
As a result[6], the FDA marketing label for Copaxone does not have an indication for reducing the progression of disability.
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.
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. [7]
Various clinical trials in glatiramer acetate are on-going. This includes studies with a higher dose of glatiramer acetare ( 40 mg - the FORTE study); studies in Clinically Isolated Syndrome patients (the PreCISe study) as well as numerous combination and induction protocols, in which glatiramer acetate is given together with or following another active product.
Etymology
The proper name of the drug is derived from its component amino acids: glutamic acid, lysine, alanine, and tyrosine. Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its Lysine (abbreviated as Lys or K) is an α- Amino acid with the Chemical formula HO2CCH(NH2(CH24NH2 Alanine (abbreviated as Ala or A) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH3 Tyrosine (abbreviated as Tyr or Y) or 4-hydroxyphenylalanine, is one of the 20 Amino acids that are used by cells to synthesize
References
- ^ FDA Copaxone Label: http://www.fda.gov/cder/foi/label/2001/20622s15lbl.pdf
- ^ http://www.copaxone.com/pdf/PrescribingInformation.pdf
- ^ the 9006 trial; Cohen JA et al. Neurology. 2007;68:939-944)
- ^ Cochrane Medical review of Copaxone - http://www.cochrane.org/reviews/en/ab004678.html
- ^ FDA marketing label - http://www.copaxone.com/pdf/PrescribingInformation.pdf
- ^ Copaxone marketing materials - http://www.copaxone.com/NewlyDiagnosed/pivotTrial.aspx
- ^ Wolinsky J, Narayana P, O'Connor P et al. (2007). "Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial". Ann Neurol 61 (1): 14–24. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17262850.
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