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Demonstration of Biological and Immunological Equivalence of a Generic Glatiramer Acetate

Author(s):

Josephine D D`Alessandro, Kevin Garofalo, Ganlin Zhao, Christopher Honan, Jay Duffner, Ishan Capila, Ian Fier, Ganesh Kaundinya, Daniel Kantor and Tanmoy Ganguly   Pages 1 - 10 ( 10 )

Abstract:


In April 2015, the US Food and Drug Administration approved the first generic glatiramer acetate, Glatopa® (M356), as fully substitutable for Copaxone® 20 mg/mL for relapsing forms of multiple sclerosis (MS). This approval was accomplished through an Abbreviated New Drug Application that demonstrated equivalence to Copaxone. In vitro and in vivo experiments from multiple redundant orthogonal assays within four biological processes (aggregate biology, antigen-presenting cell biology, T-cell biology, and B-cell biology) modulated by glatiramer acetate in MS established the biological and immunological equivalence of Glatopa and Copaxone and are described. The following were observed when comparing Glatopa and Copaxone: equivalent delays in symptom onset and reductions in “disease” intensity in experimental autoimmune encephalomyelitis; equivalent dose-dependent increases in Glatopa- and Copaxone-induced monokine-induced interferon-gamma release from THP-1 cells; a shift to a T helper 2 phenotype resulting in the secretion of interleukin (IL)-4 and downregulation of IL-17 release; no differences in immunogenicity and the presence of equivalent “immunofingerprints” between both versions of glatiramer acetate; and no stimulation of histamine release with either glatiramer acetate in basophilic leukemia 2H3 cell lines. This comprehensive approach across different biological and immunological pathways modulated by glatiramer acetate consistently supported the biological and immunological equivalence of Glatopa and Copaxone.

Keywords:

Antigen-presenting cell, B cell, glatiramer acetate, generic, multiple sclerosis, T cell

Affiliation:

Research department, Momenta Pharmaceuticals, Inc., Cambridge, MA,, Research department, Momenta Pharmaceuticals, Inc., Cambridge, MA,, Division of Bioequivalence I, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD,, Research department, Momenta Pharmaceuticals, Inc., Cambridge, MA,, Research department, Momenta Pharmaceuticals, Inc., Cambridge, MA,, Research department, Momenta Pharmaceuticals, Inc., Cambridge, MA,, Research department, Momenta Pharmaceuticals, Inc., Cambridge, MA,, Research department, Momenta Pharmaceuticals, Inc., Cambridge, MA,, Division of Neurology, Florida Atlantic University, Boca Raton, FL,, Research department, Momenta Pharmaceuticals, Inc., Cambridge, MA



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