Extensive preclinical evaluation of an infliximab biosimilar candidate

• Published in: European journal of pharmaceutical sciences Vol. 102; pp. 35 - 45
• Main Authors: Velasco-Velázquez, MA, Salinas-Jazmín, N., Hisaki-Itaya, E., Cobos-Puc, L., Xolalpa, W., González, G., Tenorio-Calvo, A., Piña-Lara, N., Juárez-Bayardo, LC, Flores-Ortiz, LF, Medina-Rivero, E., Pérez, NO, Pérez-Tapia, SM
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2017
• Subjects: Animals; anti-TNF-α; Antirheumatic Agents - pharmacokinetics; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis - drug therapy; Arthritis - metabolism; Biosimilar; Biosimilar Pharmaceuticals - pharmacokinetics; Biosimilar Pharmaceuticals - pharmacology; Biosimilar Pharmaceuticals - therapeutic use; Cells, Cultured; CHO Cells; Cricetulus; Cytokines - genetics; Cytokines - metabolism; E-Selectin - metabolism; HEK293 Cells; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Infliximab; Infliximab - pharmacokinetics; Infliximab - pharmacology; Infliximab - therapeutic use; Intercellular Adhesion Molecule-1 - metabolism; Male; Mice; Mice, Transgenic; Rheumatoid arthritis; Therapeutic mAb; TNF-α; Vascular Cell Adhesion Molecule-1 - metabolism; Infliximab; TNF-α; anti-TNF-α; Rheumatoid arthritis; Biosimilar; Therapeutic mAb
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2017.01.038

Infliximab is therapeutic monoclonal antibody (mAb) against TNF-α employed in the treatment of immunoinflammatory diseases. The development of biosimilar mAbs is a global strategy to increase drug accessibility and reduce therapy-associated costs. Herein we compared key physicochemical characteristics and biological activities produced by infliximab and infliximab-Probiomed in order to identify functionally relevant differences between the mAbs. Binding of infliximab-Probiomed to TNF-α was specific and had kinetics comparable to that of the reference product. Both mAbs had highly similar neutralizing efficacy in HUVEC cell cultures stimulated with TNF-α. In vitro induction of CDC and ADCC were also similar between the evaluated products. In vivo comparability was assessed using a transgenic mouse model of arthritis that expresses human TNF-α in a 13-week multiple-administration study. Infliximab and infliximab-Probiomed showed comparable efficacy, safety, and pharmacokinetic profiles. Our results indicate that infliximab-Probiomed has highly similar activities to infliximab in preclinical models, warranting a clinical evaluation of its biosimilarity. [Display omitted]