title: New Alternatives for Autoimmune Disease Treatments: Physicochemical and Clinical Comparability of Biosimilar Etanercept.
abstract: Etanercept is a recombinant fusion protein approved for the treatment of TNF-α mediated diseases such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, and ankylosing spondylitis. Herein, we present an evaluation of the physicochemical and biological properties of a biosimilar etanercept and its reference product followed by a clinical study in patients diagnosed with RA intended to demonstrate comparability of their immunomodulatory activity. Identity analyses showed a total correspondence of the primary and higher-order structure between the two products. In regard to intrinsic heterogeneity, both products showed to be highly heterogenous; however the biosimilar etanercept exhibited similar charge and glycan heterogeneity intervals compared to the reference product. Apoptosis inhibition assay also showed that, despite the high degree of heterogeneity exhibited by both products, no significant differences exist in their in vitro activity. Finally, the clinical assessment conducted in RA-diagnosed patients did not show significant differences in the evaluated pharmacodynamic markers of both products. Collectively, the results from the comparability exercise provide convincing evidence that the evaluated biosimilar etanercept can be considered an effective alternative for the treatment of RA.
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de Carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Mariana P
authors.initials: MP
authors.lastname: Miranda-Hernández
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de Carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: López-Morales
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de Carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Francisco C
authors.initials: FC
authors.lastname: Perdomo-Abúndez
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de Carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Rodolfo D
authors.initials: RD
authors.lastname: Salazar-Flores
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de Carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Ramírez-Ibanez
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de Carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Nestor O
authors.initials: NO
authors.lastname: Pérez
authors.affiliation: Dirección Médica, Probiomed S.A. de C.V., Avenida Ejército Nacional No. 499, Colonia Granada, Delegación Miguel Hidalgo, 11520 Mexico, DF, Mexico.
authors.forename: Aarón
authors.initials: A
authors.lastname: Molina-Pérez
authors.affiliation: Dirección Médica, Probiomed S.A. de C.V., Avenida Ejército Nacional No. 499, Colonia Granada, Delegación Miguel Hidalgo, 11520 Mexico, DF, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Revilla-Beltri
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de Carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Flores-Ortiz
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de Carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Emilio
authors.initials: E
authors.lastname: Medina-Rivero
mesh_terms: D000595:Amino Acid Sequence; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D015415:Biomarkers; D059451:Biosimilar Pharmaceuticals / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D002460:Cell Line; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D056747:Immunomodulation / Q000187:drug effects; D013058:Mass Spectrometry; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D015415:Biomarkers; D059451:Biosimilar Pharmaceuticals; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept