The online version of this article (doi:10.1007/s00280-016-3001-2) contains supplementary material, which is available to authorized users.
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.
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.
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.
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.
Fig. S1 Study design. a Hours at which samples were collected for ADA. Samples for PK were collected at all times shown. ADA antidrug antibody; AE adverse event, PK pharmacokinetics. (EPS 1968 kb)280_2016_3001_MOESM1_ESM.eps
Fig. S2 Individual and geometric mean C max, AUC0-t , and AUC0-∞ for PF-06439535, bevacizumab-EU, and bevacizumab-US. (a) C max; (b) AUC0-t ; and (c) AUC0-∞ . Stars (★) represent geometric mean and circles (o) represent individual subject values. Box plot provides median and 25 %/75 % quartiles with whiskers to the last point within 1.5 × inter-quartile range. AUC 0-∞ area under the serum concentration-time profile from zero extrapolated to infinite time; AUC 0-t area under the serum concentration-time profile from zero to the time of the last quantifiable concentration; C max maximum observed serum concentration. (EPS 2415 kb)280_2016_3001_MOESM2_ESM.eps
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- A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers
- Springer Berlin Heidelberg
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