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, 25 mg/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 (C(max)) and the area under the concentration-time curve from time 0 to the last measurable time point (AUC(0-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 C(max) and AUC(0-t) values of the reference product (mean ± standard deviation) were 1.25 ± 0.45 mg/L and 283.15 ± 98.57 mg*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 C(max) and AUC(0-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®.