In this study, physicochemical and functional similarity were assessed between PF-05280014, trastuzumab-US and trastuzumab-EU using peptide mapping. In vitro functional similarity was assessed using a tumour cell proliferation inhibition assay using the HER2-overexpression metastatic breast carcinoma cell line, SKBR-3. To determine the in vivo pharmacokinetics/tolerability male CD-1 mice were administered a single-dose (0, 1, 10, or 100 mg/kg) of PF-05280014, trastuzumab-US or trastuzumab-EU.

The results of peptide mapping of PF-05280014, trastuzumab-US, and trastuzumab-EU showed similar chromatographic profiles between the three drugs. The tumour cell growth inhibition of PF-05280014 was similar to trastuzumab-US and trastuzumab-EU. C_max and area under the concentration time curve (AUC) values in mice were similar and dose-dependent across the three monoclonal antibodies at all doses. Clearance (CL) and volume of distribution (V_ss) values were also similar and dose-independent. The incidence of anti-drug antibodies was low (~10%) and also similar across all dose levels and the three monoclonal antibodies.

PF-05280014, trastuzumab-US, and trastuzumab-EU were well tolerated during the 4-month observation period following a single dose of up to 100 mg/kg.

The authors therefore concluded that the results of these studies support the development of PF-05280014 as a proposed biosimilar to Herceptin (trastuzumab).

Conflict of interest
This study was funded by Pfizer. All authors of the of the research paper [1] are employees of either Pfizer or Covance, contracted by Pfizer for this study.

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Reference
1. Hurst S, et al. Comparative nonclinical assessments of the proposed biosimilar PF-05280014 and Trastuzumab (Herceptin®). BioDrugs. 2014. [Epub ahead of print]

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