title: Equivalent Gene Expression Profiles between Glatopa™ and Copaxone®.
abstract: Glatopa™ is a generic glatiramer acetate recently approved for the treatment of patients with relapsing forms of multiple sclerosis. Gene expression profiling was performed as a means to evaluate equivalence of Glatopa and Copaxone®. Microarray analysis containing 39,429 unique probes across the entire genome was performed in murine glatiramer acetate--responsive Th2-polarized T cells, a test system highly relevant to the biology of glatiramer acetate. A closely related but nonequivalent glatiramoid molecule was used as a control to establish assay sensitivity. Multiple probe-level (Student's t-test) and sample-level (principal component analysis, multidimensional scaling, and hierarchical clustering) statistical analyses were utilized to look for differences in gene expression induced by the test articles. The analyses were conducted across all genes measured, as well as across a subset of genes that were shown to be modulated by Copaxone. The following observations were made across multiple statistical analyses: the expression of numerous genes was significantly changed by treatment with Copaxone when compared against media-only control; gene expression profiles induced by Copaxone and Glatopa were not significantly different; and gene expression profiles induced by Copaxone and the nonequivalent glatiramoid were significantly different, underscoring the sensitivity of the test system and the multiple analysis methods. Comparative analysis was also performed on sets of transcripts relevant to T-cell biology and antigen presentation, among others that are known to be modulated by glatiramer acetate. No statistically significant differences were observed between Copaxone and Glatopa in the expression levels (magnitude and direction) of these glatiramer acetate-regulated genes. In conclusion, multiple methods consistently supported equivalent gene expression profiles between Copaxone and Glatopa.
authors.affiliation: Momenta Pharmaceuticals, Inc., Cambridge, MA, United States of America.
authors.forename: Josephine S
authors.initials: JS
authors.lastname: D'Alessandro
authors.affiliation: Momenta Pharmaceuticals, Inc., Cambridge, MA, United States of America.
authors.forename: Jay
authors.initials: J
authors.lastname: Duffner
authors.affiliation: Momenta Pharmaceuticals, Inc., Cambridge, MA, United States of America.
authors.forename: Joel
authors.initials: J
authors.lastname: Pradines
authors.affiliation: Momenta Pharmaceuticals, Inc., Cambridge, MA, United States of America.
authors.forename: Ishan
authors.initials: I
authors.lastname: Capila
authors.affiliation: Momenta Pharmaceuticals, Inc., Cambridge, MA, United States of America.
authors.forename: Kevin
authors.initials: K
authors.lastname: Garofalo
authors.affiliation: Momenta Pharmaceuticals, Inc., Cambridge, MA, United States of America.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Kaundinya
authors.affiliation: The University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Greenberg
authors.affiliation: Kantor Neurology, Coconut Creek, FL, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kantor
authors.affiliation: Momenta Pharmaceuticals, Inc., Cambridge, MA, United States of America.
authors.forename: Tanmoy C
authors.initials: TC
authors.lastname: Ganguly
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D000068717:Glatiramer Acetate / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000068717:Glatiramer Acetate