Abstract
Objective: HD203 is a biosimilar of etanercept, a fusion protein of the ligand-binding portion of the human tumor necrosis factor receptor II linked to the Fc portion of human immunoglobulin G1. Since HD203 is under clinical development, this study was conducted to compare the pharmacokinetics of HD203 with Enbrel ®, the first marketed etanercept.
Methods: A double-blind, randomized, single-dose, two-period, two-sequence, crossover study was conducted in 37 healthy volunteers. In each period, 25mg/mL of reconstituted lyophilized reference (Enbrel®) or test product (HD203) was administered subcutaneously, either the reference product followed by the test product, or vice versa. Serial blood samples for pharmacokinetic analysis were taken for 480 hours after dosing, and serum concentrations of the products were determined using a commercial enzyme-linked immunosorbent assay. The geometric mean ratios with 90% confidence intervals for the maximum concentration (Cmax) and the area under the concentration-time curve from time 0 to the last measurable time point (AUC0-t) were estimated.
Results: A total of 35 subjects completed the study; serious adverse events were not observed. The mean serum concentration-time profiles of the two products were similar. The Cmax and AUC0-t values of the reference product (mean±standard deviation) were 1.25±0.45mg/L and 283.15 ± 98.57mg*h/L, respectively, while those of the test drug were 1.35 ± 0.47 mg/L and 315.78±99.38 mg*h/L, respectively. The geometric mean ratios (90% confidence intervals) of the test to the reference for Cmax and AUC0-t were 1.08 (1.00, 1.16) and 1.13 (1.05, 1.21), respectively.
Conclusions: A single subcutaneous injection of HD203 or Enbrel ® into healthy volunteers appeared to be safe and well tolerated. Comparative pharmacokinetics demonstrated that reconstituted lyophilized HD203 has bioavailability similar to that of Enbrel®.
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Acknowledgements
This study, which was sponsored by Hanwha Chemical Co. Ltd., Seoul, Korea, was designed and conducted by the Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, and was conducted by qualified investigators. None of the authors have any conflicts of interest to disclose regarding the content of this article. All co-authors were involved in writing the manuscript. SoJeong Yi and Sung Eun Kim received a training program grant from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare Affairs of the Republic of Korea (KoNECT, A070001).
The authors would like to thank Ms. Geum Jwa Ryu (Clinical Pharmacology and Bioanalytical Research Team, Seoul National University College of Medicine and Hospital) for bioanalytical assays and Ms. Hyun-Jung Kim (Clinical Trials Center, Seoul National University Hospital) for assistance as a clinical research coordinator.
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Yi, S.J., Kim, S.E., Park, MK. et al. Comparative Pharmacokinetics of HD203, a Biosimilar of Etanercept, with Marketed Etanercept (Enbrel ®). BioDrugs 26, 177–184 (2012). https://doi.org/10.2165/11631860-000000000-00000
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DOI: https://doi.org/10.2165/11631860-000000000-00000