Functional and Nonclinical Similarity of ABP 980, a Biosimilar of Trastuzumab

• Published in: Pharmaceutical research 2019-12, Vol.36 (12), p.177-18, Article 177
• Main Authors: Jassem, Shea, Wang, Wei, Sweet, Heather, Manoukian, Raffi, Chow, Vincent, Kanakaraj, Palanisamy, Hutterer, Katariina M., Kuhns, Scott, Foltz, Ian N., Chen, Qing, Ferbas, John, McBride, Helen J.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Binding, Competitive; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Biosimilar Pharmaceuticals - chemistry; Breast cancer; Breast Neoplasms - drug therapy; Cancer; Cell Line, Tumor; Chemotherapy; Epidermal growth factor; ErbB-2 protein; Female; Gastric cancer; Humans; Immunotherapy; Internalization; Kinetics; Medical Law; Medical research; Medicine, Experimental; Mice, Nude; Molecular Structure; Monoclonal antibodies; Monocytes; Natural killer cells; Neoplasms, Experimental; Phagocytosis; Pharmacology/Toxicology; Pharmacy; Protein Binding; Receptor, ErbB-2 - chemistry; Research Paper; Signal Transduction; Stomach Neoplasms - drug therapy; Structure-Activity Relationship; Targeted cancer therapy; Trastuzumab; Trastuzumab - chemistry; Xenografts
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-019-2702-8

Purpose The in vitro and in vivo pharmacologic assessment of ABP 980 similarity to its reference product is intended to compare the activity of ABP 980 and trastuzumab and support the overall conclusion of similarity based on a comprehensive analytical and functional evaluation. Methods This work complements the primary assessment of functional similarity with additional in vitro assays, binding studies, and non-clinical studies including human epidermal growth factor receptor-2 (HER2) kinetic binding, HER2 signaling, HER2 internalization, synergy with docetaxel chemotherapy, FcγR kinetic binding, primary natural killer and monocyte cell binding, antibody-dependent cellular phagocytosis activity, in vivo xenograft studies, and toxicokinetic parameters. Results The results contribute to the totality of evidence with respect to functional similarity and support that ABP 980 is similar to trastuzumab in all primary and secondary mechanisms of action. Conclusions These results also support the scientific justification of extrapolation to all approved indications of trastuzumab given the established functional similarity of the two products and the same mechanisms of action across all conditions of use.