The researchers say that their data were consistent with the pharmacokinetic equivalence previously demonstrated in a single-dose PK study that included 202 healthy adult men in the United States and European Union, and thus add to the evidence of ABP-215 as a high-quality biosimilar to bevacizumab for use in Japan.
A phase 1 equivalence study of ABP-215 (Mvasi, the first FDA-approved biosimilar bevacizumab) concludes that ABP-215 demonstrated pharmacokinetic (PK) similarity to the reference drug in healthy Japanese men.1 ABP-215 is an inhibitor of blood vessel growth and is approved in the United States for chemotherapy and targeted therapy for colorectal, lung, glioblastoma, kidney, and cervical cancer.
Safety profiles were comparable between subjects dosed with the reference and the biosimilar, and PK data in Japanese subjects were consistent with those previously shown in global studies.
The study, funded by Amgen, was published by Vladimir Hanes, MD, and colleagues in Cancer Chemotherapy and Pharmacology.
The randomized, single-blind, single-dose, parallel-group study had as its primary endpoints maximum observed serum concentration (Cmax) and area under the serum concentration—time curve from time 0 to infinity (AUCinf). Secondary endpoints included AUC from time 0 to time of last quantifiable concentration (AUClast), safety, tolerability, and immunogenicity. The study lasted 57 days.
Each of the 2 study groups had 24 subjects; all had similar baseline characteristics and were between 18 and 45 years of age. All 48 study subjects completed the infusion; 46 completed the study because 2 were lost to follow-up.
After a 3-mg/kg IV infusion, the geometric means (GM) of Cmax, AUCinf, and AUClast were71.2 μg/mL, 25,259 μg h/mL, and 22,499.3 μg h/mL, respectively, for ABP-215 and 70.16 μg/mL, 25,801 μg h/mL, and 22,604.6 μg h/mL, respectively, for bevacizumab. The GM ratios (90% CI) for Cmax, AUCinf, and AUClast were 1.015 (0.946-1.088), 0.979 (0.914-1.049), and 0.995 (0.941-1.053) for ABP-215 versus bevacizumab. All confidence intervals were within the prespecified bioequivalence margin of 0.80-1.25.
Adverse events (AEs) occurred in 2 of 24 subjects receiving ABP-215 and 1 of 24 receiving reference drug. No subject experienced an infusion reaction or hypersensitivity AE in the first 2 days after study drug administration. There were no deaths or AEs leading to discontinuation, and no patient was positive for binding anti-drug antibodies.
The researchers concluded that their data were consistent with the PK equivalence previously demonstrated in a single-dose PK study that included 202 healthy adult men in the United States and European Union, and thus add to the evidence of ABP-215 as a high-quality biosimilar to bevacizumab for use in Japan.
Hanes V, Chow V, Pan Z, Markus R. A randomized, single-blind, single-dose study to assess the pharmacokinetic equivalence of the biosimilar ABP 215 and bevacizumab in healthy Japanese male subjects. Cancer Chemother Pharmacol. 2018;82:899-905. doi: 10.1007/s00280-018-3695-4.