Background: 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.
Method: This article will provide an overview of the methods used to establish the biological and immunological
equivalence of the two glatiramer acetate products, including methods evaluating antigenpresenting
cell (APC) biology, T-cell biology, and other immunomodulatory effects.
Results: In vitro
and in vivo
experiments from multiple redundant orthogonal assays within four biological
processes (aggregate biology, APC 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 in
these experiments: 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.
Conclusion: In summary, this comprehensive approach across different biological and immunological
pathways modulated by glatiramer acetate consistently supported the biological and immunological
equivalence of Glatopa and Copaxone.