Contributions
Abstract: EP1651
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background and objectives: Given its structural and compositional complexity, Copaxone (Teva, glatiramer acetate) cannot be fully characterized using current state-of-the-art methodologies. As studies indicate a correlation between surface charge and immunogenicity of polypeptides (Foged C Int J Pharm 2005; Bhattacharjee S Part Fibre Toxicol 2010; Fromen CA Nanomedicine 2016), Teva employed a gold standard for charge-sensitive antibody analysis, Cation Exchange Chromatography (CEX), to further assess the surface charge attributes of Copaxone and compare them to follow-on glatiramer acetate (FOGA) products marketed in Europe, the USA, Russia and Latin America.
Methods: CEX is based on a non-destructive separation of polypeptide mixtures into subgroups according to their average overall surface charge. Copaxone samples consistently comprise of three subpopulations represented by distinct peaks on CEX chromatograms: weak negatively charged, weak positively charged, and strong positively charged polypeptide subpopulations.
Results: The charge distribution for the marketed batches of FOGAs differed from that of Copaxone batches in terms of the distribution of the typical three distinct subpopulations. Charge distribution values of Polimunol (Argentina), Axoglatiran (Russia), and Synthon's European FOGA (Europe) were outside the Copaxone range of values for the negatively charged subpopulation and weak positively charged subpopulation. For the strongly positively charged distribution, all of Polimunol and Axoglatiran batches and 4 of 6 batches of the Synthon European product were above the Copaxone range. Glatopa batches demonstrated inconsistent results with the negative subpopulation varying from higher to significantly lower values than Copaxone thresholds; weak positive distributions were lower than Copaxone in all batches; and strongly positive subpopulation were higher than the Copaxone range in six out of eight batches.
Conclusion: All tested FOGA products demonstrated varying degrees of altered surface charge relative to Copaxone. Since this hypothesis has already been confirmed for Polimunol and Glatopa, showing robust differences in gene expression profiles of immune-mediated inflammatory pathways (Laifenfeld Ectrims 2016; Kolitz Ectrims 2016, respectively), further investigation of FOGA-induced immunogenicity is warranted.
Disclosure: All authors are employees of Teva Pharmaceutical Industries, the sponsor of the research conducted in this report.
Abstract: EP1651
Type: ePoster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background and objectives: Given its structural and compositional complexity, Copaxone (Teva, glatiramer acetate) cannot be fully characterized using current state-of-the-art methodologies. As studies indicate a correlation between surface charge and immunogenicity of polypeptides (Foged C Int J Pharm 2005; Bhattacharjee S Part Fibre Toxicol 2010; Fromen CA Nanomedicine 2016), Teva employed a gold standard for charge-sensitive antibody analysis, Cation Exchange Chromatography (CEX), to further assess the surface charge attributes of Copaxone and compare them to follow-on glatiramer acetate (FOGA) products marketed in Europe, the USA, Russia and Latin America.
Methods: CEX is based on a non-destructive separation of polypeptide mixtures into subgroups according to their average overall surface charge. Copaxone samples consistently comprise of three subpopulations represented by distinct peaks on CEX chromatograms: weak negatively charged, weak positively charged, and strong positively charged polypeptide subpopulations.
Results: The charge distribution for the marketed batches of FOGAs differed from that of Copaxone batches in terms of the distribution of the typical three distinct subpopulations. Charge distribution values of Polimunol (Argentina), Axoglatiran (Russia), and Synthon's European FOGA (Europe) were outside the Copaxone range of values for the negatively charged subpopulation and weak positively charged subpopulation. For the strongly positively charged distribution, all of Polimunol and Axoglatiran batches and 4 of 6 batches of the Synthon European product were above the Copaxone range. Glatopa batches demonstrated inconsistent results with the negative subpopulation varying from higher to significantly lower values than Copaxone thresholds; weak positive distributions were lower than Copaxone in all batches; and strongly positive subpopulation were higher than the Copaxone range in six out of eight batches.
Conclusion: All tested FOGA products demonstrated varying degrees of altered surface charge relative to Copaxone. Since this hypothesis has already been confirmed for Polimunol and Glatopa, showing robust differences in gene expression profiles of immune-mediated inflammatory pathways (Laifenfeld Ectrims 2016; Kolitz Ectrims 2016, respectively), further investigation of FOGA-induced immunogenicity is warranted.
Disclosure: All authors are employees of Teva Pharmaceutical Industries, the sponsor of the research conducted in this report.