Purpose This study compared the pharmacokinetics of\nPF-06439535, a potential bevacizumab biosimilar, to bevacizumab\nsourced from the European Union (bevacizumab-\nEU) and USA (bevacizumab-US), and of bevacizumab-EU\nto bevacizumab-US.\nMethods In this double-blind study, 102 healthy males,\naged 21ââ?¬â??55 years, were randomized 1:1:1 to receive a\nsingle 5 mg/kg intravenous dose of PF-06439535, bevacizumab-\nEU, or bevacizumab-US. Pharmacokinetic assessments\nwere conducted for 71 days, with additional safety\nand immunogenicity assessments until day 100. Pharmacokinetic\nsimilarity was achieved if 90 % confidence intervals\n(CIs) for the test-to-reference ratios of the maximum\nserum concentration (Cmax), area under the serum concentrationââ?¬â??\ntime curve from zero to infinity (AUC0ââ?¬â??âË?ž), and\nfrom zero to time of last quantifiable concentration (AUC0ââ?¬â??\nt) were within the 80.00ââ?¬â??125.00 % bioequivalence acceptance\nwindow. Results The three study drugs exhibited similar pharmacokinetic\nproperties. For the comparisons of PF-06439535\nto bevacizumab-EU or bevacizumab-US, and of bevacizumab-\nEU to bevacizumab-US, the 90 % CIs for the\nratios of Cmax, AUC0ââ?¬â??t, and AUC0ââ?¬â??âË?ž were all within\n80.00ââ?¬â??125.00 %. Two, one, and two subjects treated with\nPF-06439535, bevacizumab-EU, and bevacizumab-US,\nrespectively, tested positive for antidrug antibodies, none\nof whom tested positive for neutralizing antibodies. Treatment-\nrelated adverse events were reported in 15.2, 25.7,\nand 18.2 % of subjects in the PF-06439535, bevacizumab-\nEU, and bevacizumab-US treatment arms, respectively.\nConclusions This study demonstrated the pharmacokinetic\nsimilarity of PF-06439535 to both bevacizumab-EU\nand bevacizumab-US, and of bevacizumab-EU to bevacizumab-\nUS. The safety profile (including immunogenicity)\nwas similar in the three treatment groups, with no significant\nsafety findings reported.
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