A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers.
PURPOSE: This study compared the pharmacokinetics of PF-06439535, a potential bevacizumab biosimilar, to bevacizumab sourced from the European Union (bevacizumab-EU) and USA (bevacizumab-US), and of bevacizumab-EU to bevacizumab-US.
METHODS: In this double-blind study, 102 healthy males, aged 21-55 years, were randomized 1:1:1 to receive a single 5 mg/kg intravenous dose of PF-06439535, bevacizumab-EU, or bevacizumab-US. Pharmacokinetic assessments were conducted for 71 days, with additional safety and immunogenicity assessments until day 100. Pharmacokinetic similarity was achieved if 90 % confidence intervals (CIs) for the test-to-reference ratios of the maximum serum concentration (C max), area under the serum concentration-time curve from zero to infinity (AUC0-∞), and from zero to time of last quantifiable concentration (AUC0-t ) were within the 80.00-125.00 % bioequivalence acceptance window.
RESULTS: The three study drugs exhibited similar pharmacokinetic properties. For the comparisons of PF-06439535 to bevacizumab-EU or bevacizumab-US, and of bevacizumab-EU to bevacizumab-US, the 90 % CIs for the ratios of C max, AUC0-t , and AUC0-∞ were all within 80.00-125.00 %. Two, one, and two subjects treated with PF-06439535, bevacizumab-EU, and bevacizumab-US, respectively, tested positive for antidrug antibodies, none of whom tested positive for neutralizing antibodies. Treatment-related adverse events were reported in 15.2, 25.7, and 18.2 % of subjects in the PF-06439535, bevacizumab-EU, and bevacizumab-US treatment arms, respectively.
CONCLUSIONS: This study demonstrated the pharmacokinetic similarity of PF-06439535 to both bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. The safety profile (including immunogenicity) was similar in the three treatment groups, with no significant safety findings reported.