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 (Cmax), 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 Cmax, 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
European Medicines Agency (2014) Guideline on similar biological medicinal products. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/10/WC500176768.pdf. Accessed 25 Aug 2015
US Food and Drug Administration (2015) Scientific considerations in demonstrating biosimilarity to a reference product. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm291128.pdf. Accessed 1 May 2015
World Health Organization, Expert Committee on Biological Standardization (2009) Guidelines on evaluation of similar biotherapeutic products (SBPs). http://www.who.int/biologicals/areas/biological_therapeutics/BIOTHERAPEUTICS_FOR_WEB_22APRIL2010.pdf. Accessed 4 Feb 2015
Genentech Inc (2015) Avastin ® (bevacizumab) prescribing information. http://www.gene.com/download/pdf/avastin_prescribing.pdf. Accessed 20 May 2015
Grunder B, Costigan L, Johnson K, Kneeland T, Cirelli D, Dufield R, Kitchen R, Porter T, Rouse J, Rule K (2014) Characterization and similarity assessment of bevacizumab and a proposed biosimilar. Presented at: American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exhibition, San Diego, CA
Rule K, Peraza M, Shiue M, Finch G, Thibault S, Rosenberg JA, Leach MW (2015) Nonclinical development of PF-06439535, a potential biosimilar to bevacizumab. Presented at: IASLC 16th World Conference on Lung Cancer (WCLC 2015), Denver, CO
- A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers
- Springer Berlin Heidelberg
Neu im Fachgebiet Onkologie
Mail Icon II