In the double-blind, parallel-group trial, 144 healthy adult male volunteers were randomized to receive a single dose of CT-P16 (n = 47) at 5mg/kg, or the same dose of either EU-licensed (n = 49) or US-licensed (n = 48) reference bevacizumab.
The primary end points were area under the concentration–time curve (AUC) from time zero to infinity (AUC∞), AUC from time zero to the last quantifiable concentration (AUClast), and maximum serum concentration (Cmax).
PK equivalence was demonstrated if the 90% CIs of the geometric mean (GM) ratios of AUC∞, AUClast, and Cmax fell within the prespecified bioequivalence margin of 80% to 125%.
The investigators report that the 90% CIs for the GM ratios of all 3 end points fell within the prespecified bioequivalence margin, and the mean serum concentration–time profiles, secondary PK parameters, safety, and immunogenicity profiles were also comparable across all 3 groups.
According to the investigators, these data support the further development of CT-P16 as a bevacizumab biosimilar.
In addition to Celltrion, multiple biosimilar develoeprs are targeting bevacizumab, which is used to treat metastatic colorectal cancer, metastatic breast cancer, non–small cell lung cancer, and glioblastoma, and which is also increasingly used off-label to treat diseases of the eye, including diabetic retinopathy and age-related macular degeneration. TOT Biopharm, JHL Biotech, and Mylan have all disclosed clinical programs for proposed bevacizumab biosimilars; Amgen has seen both US and EU approval for its biosimilar, Mvasi, and Pfizer has received EU approval for its biosimilar, Zirabev. To date, no biosimilars for bevacizumab have been launched.
Cho SH, Han S, Ghim JL, et al. A randomized, double-blind trial comparing the pharmacokinetics of CT-P16, a candidate bevacizumab biosimilar, with its reference product in healthy adult males [published online March 9, 2019]. BioDrugs.