489P - Functional similarity assessment results comparing bevacizumab to biosimilar candidate ABP 215

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Clinical Research
Bioethics, Legal, and Economic Issues
Basic Scientific Principles
Biological Therapy
Presenter Teresa Born
Citation Annals of Oncology (2014) 25 (suppl_4): iv146-iv164. 10.1093/annonc/mdu331
Authors T.L. Born1, Q. Huynh2, A. Mathur2, J. Velayudhan2, J. Canon3, K. Reynhardt4, T.J. Goletz4, R.A. Markus5
  • 1Biosimilars Process Development, Amgen, Inc., 98119 - Seattle/US
  • 2Biofunctional Characterization, Amgen, Seattle/US
  • 3Oncology Research, Amgen, Thousand Oaks/US
  • 4Clinical Immunology, Amgen, Seattle/US
  • 5Biosimilars, Amgen, Thousand Oaks/US



ABP 215 is being developed as a biosimilar to bevacizumab, a recombinant monoclonal antibody that binds vascular endothelial growth factor (VEGF) and inhibits binding to receptors. Although bevacizumab and intended biosimilars share the same amino acid sequence, differences will likely exist in product quality attributes due to differences in expression systems, bioprocess and purification. Equivalence of product quality attributes, especially functional equivalence, is of primary importance during stepwise development of a biosimilar in order to provide confidence for similar clinical safety and efficacy in patients. Functional equivalence to bevacizumab is also a critical consideration when considering extrapolation of indications for the candidate biosimilar product. The aim of these studies is to examine functional simiarlity of ABP 215 to bevacizumab.


Comparative assessment of biological activity included testing binding of ABP 215 and bevacizumab to VEGF and VEGF isoforms by surface plasmon resonance and to cell-surface expressed FcRn and to FcgRIIIa by AlphaLISA. The inhibition of proliferation and VEGFR2 autophosphorylation was compared in human umbilical vein endothelial cells. Anti-tumor activity was compared in A431 and Colo205 tumor xenograft models.


Equilibrium binding affinity (Kd) to VEGF was similar between ABP 215 (117 pM) and bevacizumab (112 pM). Binding to VEGF165 and VEGF121 was also similar. Binding (3 lots each) to FcRn was similar between ABP 215 (95-102%) and bevacizumab (114-127%) as was binding to FcgRIIIa comparing ABP 215 (100-115%) to bevacizumab (100-105%). Potency in proliferation inhibition was similar across three lots each of bevacizumab (87-98%) compared to ABP 215 (92-101%). Inhibition of autophosphorylation (IC50) was similar for a single lot each of ABP 215 (0.0871 µg/ml) compared to bevacizumab (0.0858 µg/ml). The effects of ABP 215 and bevacizumab were also similar in vivo, in terms of inhibition of both tumor growth and tumor-associated vasculature in A431 and Colo205 models.


ABP 215 appears to be highly similar to bevacizumab in multiple sensitive preclinical pharmacologic assessments.


T.L. Born: author is a stockholder and emplyoee of of Amgen; Q. H uynh, A. Mathur, J. Velayudhan, J. Canon, K. Reynhardt, T.J. Goletz and R.A. Markus: Amgen employee and stockholder