title: Comparing the biological impact of glatiramer acetate with the biological impact of a generic.
abstract: For decades, policies regarding generic medicines have sought to provide patients with economical access to safe and effective drugs, while encouraging the development of new therapies. This balance is becoming more challenging for physicians and regulators as biologics and non-biological complex drugs (NBCDs) such as glatiramer acetate demonstrate remarkable efficacy, because generics for these medicines are more difficult to assess. We sought to develop computational methods that use transcriptional profiles to compare branded medicines to generics, robustly characterizing differences in biological impact. We combined multiple computational methods to determine whether differentially expressed genes result from random variation, or point to consistent differences in biological impact of the generic compared to the branded medicine. We applied these methods to analyze gene expression data from mouse splenocytes exposed to either branded glatiramer acetate or a generic. The computational methods identified extensive evidence that branded glatiramer acetate has a more consistent biological impact across batches than the generic, and has a distinct impact on regulatory T cells and myeloid lineage cells. In summary, we developed a computational pipeline that integrates multiple methods to compare two medicines in an innovative way. This pipeline, and the specific findings distinguishing branded glatiramer acetate from a generic, can help physicians and regulators take appropriate steps to ensure safety and efficacy.
authors.affiliation: Immuneering Corporation, Cambridge, Massachusetts, United States of America.
authors.forename: Fadi
authors.initials: F
authors.lastname: Towfic
authors.affiliation: Immuneering Corporation, Cambridge, Massachusetts, United States of America.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Funt
authors.affiliation: Immuneering Corporation, Cambridge, Massachusetts, United States of America.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Fowler
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Bakshi
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Blaugrund
authors.affiliation: Immuneering Corporation, Cambridge, Massachusetts, United States of America.
authors.forename: Maxim N
authors.initials: MN
authors.lastname: Artyomov
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Ladkani
authors.affiliation: Teva Pharmaceutical Industries, Petach Tikva, Israel.
authors.forename: Rivka
authors.initials: R
authors.lastname: Schwartz
authors.affiliation: Immuneering Corporation, Cambridge, Massachusetts, United States of America.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Zeskind
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D016568:Drugs, Generic / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D000068717:Glatiramer Acetate; D007107:Immune System / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D015415:Biomarkers; D016568:Drugs, Generic; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C501984:Gpr83 protein, mouse; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D000068717:Glatiramer Acetate