title: The glatiramoid class of immunomodulator drugs.
abstract: Glatiramer acetate (GA) is a complex heterogenous mixture of polypeptides with immunomodulatory activity approved for treatment of relapsing-remitting multiple sclerosis. GA is the first, and was until recently, the only member of the glatiramoids, a family of synthetic copolymer mixtures comprising the four amino acids, L-glutamic acid, L-alanine, L-lysine and L-tyrosine, in a defined molar ratio. Another glatiramoid, protiramer, was recently evaluated in preclinical studies and in two small Phase II clinical trials with relapsing-remitting multiple sclerosis patients. Due to the complexity and heterogeneity of GA and other glatiramoids, the clinically active epitopes within the mixture cannot be identified and the consistency of polypeptide sequences within the mixture is dependent on a tightly controlled manufacturing process. Although no two glatiramoids can be proved identical, it is possible to differentiate among members of the glatiramoid class using analytical methods and immunological and biological markers. Even slight differences in the distribution of molecular masses or in the composition of antigenic polypeptide sequences among glatiramoids can significantly influence their efficacy, toxicity and immunogenicity profiles. Experience with GA may be instructive regarding important safety and efficacy considerations for new glatiramoid mixtures now in development.
authors.affiliation: Innovative R&D Division TEVA Pharmaceutical Industries, Netanya, Israel. haim.varkony@teva.co.il
authors.forename: Haim
authors.initials: H
authors.lastname: Varkony
authors.forename: Vera
authors.initials: V
authors.lastname: Weinstein
authors.forename: Ety
authors.initials: E
authors.lastname: Klinger
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sterling
authors.forename: Helena
authors.initials: H
authors.lastname: Cooperman
authors.forename: Turi
authors.initials: T
authors.lastname: Komlosh
authors.forename: David
authors.initials: D
authors.lastname: Ladkani
authors.forename: Rivka
authors.initials: R
authors.lastname: Schwartz
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D000068717:Glatiramer Acetate; D006801:Humans; D008970:Molecular Weight; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D018675:Toxicity Tests
chemical_list: D000276:Adjuvants, Immunologic; D010455:Peptides; D000068717:Glatiramer Acetate