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Neurology and Therapy
Published in: Neurology and Therapy 2/2017

Open Access 01-12-2017 | Review

A Comprehensive Review on Copemyl®

Authors: Pietro Annovazzi, Antonio Bertolotto, Vincenzo Brescia Morra, Claudio Gasperini, Enrico Montanari, Pierluigi Navarra, Francesco Patti, Maria Pia Sormani, Angelo Ghezzi

Published in: Neurology and Therapy | Issue 2/2017

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Abstract

Economic sustainability is of paramount importance in the rapidly evolving therapeutic scenario of multiple sclerosis (MS). Glatiramoids are a class of drugs whose forefather, glatiramer acetate, has been used as a disease modifying drug (DMD) in patients with MS for over 20 years. Its patent expired in 2015; new versions of such drug are nowadays available on the market, potentially contributing to lowering prices and enhancing a better allocation of economic resources. In this review, we analyze the recommendations underlying the approval of both generic drugs and biosimilars by regulatory authorities, and we provide methodological tools to contextualize the design of studies on these new classes of drugs. We examine in more detail the preclinical and clinical data of Copemyl®, a new member of the glatiramoid class, focusing on its biological and immunological properties and illustrating randomized controlled trials that led to its authorization.
Literature
1.
Johnson KP. Glatiramer acetate and the glatiramoid class of immunomodulator drugs in multiple sclerosis: an update. Expert Opin Drug Metab Toxicol. 2010;6(5):643–60.CrossRefPubMed
2.
Comi G, Amato MP, Bertolotto A, et al. The heritage of glatiramer acetate and its use in multiple sclerosis. Mult Scler Demyelin Disord. 2016;1:6.CrossRef
3.
Arnon R. The development of Cop 1 (Copaxone), an innovative drug for the treatment of multiple sclerosis: personal reflections. Immunol Lett. 1996;50(1–2):1–15.CrossRefPubMed
4.
Teitelbaum D, Meshorer A, Hirshfeld T, Arnon R, Sela M. Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur J Immunol. 1971;1(4):242–8.CrossRefPubMed
5.
Aharoni R, Teitelbaum D, Sela M, Arnon R. Bystander suppression of experimental autoimmune encephalomyelitis by T cell lines and clones of the Th2 type induced by copolymer 1. J Neuroimmunol. 1998;91(1–2):135–46.CrossRefPubMed
6.
Oreja-Guevara C, Ramos-Cejudo J, Aroeira LS, Chamorro B, Diez-Tejedor E. TH1/TH2 cytokine profile in relapsing-remitting multiple sclerosis patients treated with glatiramer acetate or natalizumab. BMC Neurol. 2012;12:95.CrossRefPubMedPubMedCentral
7.
Haas J, Korporal M, Balint B, Fritzsching B, Schwarz A, Wildemann B. Glatiramer acetate improves regulatory T-cell function by expansion of naïve CD4(+)CD25(+)FOXP3(+)CD31(+) T-cells in patients with multiple sclerosis. J Neuroimmunol. 2009;216(1–2):113–7.CrossRefPubMed
8.
Aharoni R, Eilam R, Stock A, et al. Glatiramer acetate reduces Th-17 inflammation and induces regulatory T-cells in the CNS of mice with relapsing-remitting or chronic EAE. J Neuroimmunol. 2010;225(1–2):100–11.CrossRefPubMed
9.
Arnon R, Aharoni R. Neurogenesis and neuroprotection in the CNS–fundamental elements in the effect of glatiramer acetate on treatment of autoimmune neurological disorders. Mol Neurobiol. 2007;36(3):245–53.CrossRefPubMed
10.
Skihar V, Silva C, Chojnacki A, et al. Promoting oligodendrogenesis and myelin repair using the multiple sclerosis medication glatiramer acetate. Proc Natl Acad Sci USA. 2009;106(42):17992–7.CrossRefPubMedPubMedCentral
11.
Gentile A, Rossi S, Studer V, et al. Glatiramer acetate protects against inflammatory synaptopathy in experimental autoimmune encephalomyelitis. J Neuroimmune Pharmacol. 2013;8(3):651–63.CrossRefPubMed
12.
Farina C, Vargas V, Heydari N, Kumpfel T, Meinl E, Hohlfeld R. Treatment with glatiramer acetate induces specific IgG4 antibodies in multiple sclerosis patients. J Neuroimmunol. 2002;123(1–2):188–92.CrossRefPubMed
13.
Johnson KP, Teitelbaum D, Arnon R, The US Phase III Copolymer 1 Study Group, et al. Antibodies to copolymer do not interfere with its clinical effect. Ann Neurol. 1995;38:973.
14.
Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. Neurology. 1995;45(7):1268–76.CrossRefPubMed
15.
Comi G, Filippi M, Wolinsky JS, European/Canadian Glatiramer Acetate Study Group. 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. Ann Neurol. 2001;49(3):290–7.CrossRefPubMed
16.
EU Definition (Directive 2001/83/EC, Annex I (=Directive 2003/63/EC)) of a biological medicinal product.
17.
Schellekens H, Klinger E, Mühlebach S, Brin JF, Storm G, Crommelin DJ. The therapeutic equivalence of complex drugs. Regul Toxicol Pharmacol. 2011;59(1):176–83.CrossRefPubMed
18.
Crommelin DJ, Shah VP, Klebovich I, et al. The similarity question for biologicals and non-biological complex drugs. Eur J Pharm Sci. 2015;76:10–7.CrossRefPubMed
19.
Crommelin DJ, Bermejo T, Bissig M, et al. Pharmaceutical evaluation of biosimilars: important differences from generic low-molecular weight pharmaceuticals. Eur J Hosp Pharm Sci. 2005;1:11–7.
20.
Schellekens H. Follow-on biologics: challenges of the ‘next generation’. Nephrol Dial Transplant. 2005;20:31–6.CrossRef
21.
22.
EMA: decentralised procedure RMS final assessment report. CMDh/200/2007 Rev. 5 December 2013.
23.
24.
25.
Wellek S, Blettner M. Establishing equivalence or non-inferiority in clinical trials: part 20 of a series on evaluation of scientific publications. Dtsch Arztebl Int. 2012;109(41):674–9.PubMedPubMedCentral
26.
Njue C. Statistical considerations for confirmatory clinical trials for similar biotherapeutic products. Biologicals. 2011;39(5):266–9.CrossRefPubMed
27.
College ter Beoordeling van Geneesmiddelen (CBG) public assessment report (PAR) Scientific discussion Glatirameeracetaat Mylan 20 mg/ml, solution for injection, pre-filled syringe (glatiramer acetate) NL/H/3213/001/DC. 6 June 2016.
28.
Arends R. Gene expression analysis between 5 GTR (20 mg/mL) batches and 5 Copaxone® (20 mg/mL) batches in THP-1 cells. Dossier NDR.NL03.39931 (1.0).
29.
Weijts F (2010) Research analytical study report on bioactivity of glatiramer acetate (GTR) towards induction and activation of glatiramer-specific T cells. Dossier RASR.NL03.GTR.10.010.01.
30.
Aharoni R, Teitelbaum D, Arnon R. T suppressor hybridomas and interleukin-2-dependent lines induced by copolymer 1 or by spinal cord homogenate down-regulate experimental allergic encephalomyelitis. Eur J Immunol. 1993;23:17–25.CrossRefPubMed
31.
Cohen J, Belova A, Selmaj K, et al. Equivalence of generic glatiramer acetate in multiple sclerosis: a randomized clinical trial. JAMA Neurol. 2015;72(12):1433–41.CrossRefPubMed
32.
33.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology. 1983;33(11):1444–52.CrossRefPubMed
34.
Sormani MP, Bonzano L, Roccatagliata L, Cutter GR, Mancardi GL, Bruzzi P. Magnetic resonance imaging as a potential surrogate for relapses in multiple sclerosis: a meta-analytic approach. Ann Neurol. 2009;65(3):268–75.CrossRefPubMed
35.
Sormani MP, Bruzzi P. MRI lesions as a surrogate for relapses in multiple sclerosis: a meta-analysis of randomised trials. Lancet Neurol. 2013;12(7):669–76.CrossRefPubMed
36.
Choice of control group and related issues in clinical trials. ICH Topic E 2000; 10.
37.
Tóthfalusi L, Endrényi L, Chow SC. Statistical and regulatory considerations in assessments of interchangeability of biological drug products. Eur J Health Econ. 2014;15:S5–11.CrossRefPubMed
38.
Wu LC, Chen F, Lee SL, Raw A, Yu LX. Building parity between brand and generic peptide products: regulatory and scientific considerations for quality of synthetic peptides. Int J Pharm. 2017;518(1–2):320–34.CrossRefPubMed
39.
40.
Mikol DD, Barkhof F, Chang P, et al. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs glatiramer acetate in relapsing MS disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol. 2008;7(10):903–14.CrossRefPubMed
41.
O’Connor P, Filippi M, Arnason B, et al. 250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study. Lancet Neurol. 2009;8(10):889–97.CrossRefPubMed
42.
Lublin FD, Cofield SS, Cutter GR, et al. Randomized study combining interferon and glatiramer acetate in multiple sclerosis. Ann Neurol. 2013;73(3):327–40.CrossRefPubMedPubMedCentral
43.
La Mantia L, Di Pietrantonj C, Rovaris M, et al. Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev. 2016;24:11.
44.
Sørensen PS. Multiple sclerosis. Generic glatiramer acetate—a step toward cheaper MS drugs? Nat Rev Neurol. 2016;12(1):5–6.CrossRefPubMed
45.
Stellmann JP, Neuhaus A, Herich L et al. Placebo cohorts in phase-3 MS treatment trials—predictors for on-trial disease activity 1990–2010 based on a meta-analysis and individual case data. PLoS One. 2012;7(11):e50347.
46.
Comi G, Martinelli V, Rodegher M, et al. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet. 2009;374(9700):1503–11.CrossRefPubMed
47.
Bourdette D, Hartung D. Equivalence of glatiramer acetate generics with branded glatiramer acetate in efficacy and cost for the treatment of multiple sclerosis. JAMA Neurol. 2015;72(12):1411–3.CrossRefPubMed
48.
Garattini L, Padula A. Why EMA should provide clearer guidance on the authorization of NBCDs in generic and hybrid applications. Expert Rev Clin Pharmacol. 2017;10(3):243–5.PubMed
49.
Crommelin DJ, de Vlieger JS, Weinstein V, et al. Different pharmaceutical products need similar terminology. AAPS J. 2014;16(1):11–4.CrossRefPubMed
50.
Nicholas JM. Complex drugs and biologics: scientific and regulatory challenges for follow-on products. Drug Inf J. 2012;46(2):197–206.CrossRef
Metadata
Title
A Comprehensive Review on Copemyl®
Authors
Pietro Annovazzi
Antonio Bertolotto
Vincenzo Brescia Morra
Claudio Gasperini
Enrico Montanari
Pierluigi Navarra
Francesco Patti
Maria Pia Sormani
Angelo Ghezzi
Publication date
01-12-2017
Publisher
Springer Healthcare
Published in
Neurology and Therapy / Issue 2/2017
Print ISSN: 2193-8253
Electronic ISSN: 2193-6536
DOI
https://doi.org/10.1007/s40120-017-0079-3

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