LBEC0101, A Proposed Etanercept Biosimilar: Pharmacokinetics, Immunogenicity, and Tolerability Profiles Compared with a Reference Biologic Product in Healthy Male Subjects

Objectives We performed this study to compare the pharmacokinetic (PK), immunogenicity, and tolerability profiles of etanercept between LBEC0101, a proposed biosimilar, and Enbrel (R), the reference biological product. Methods A randomized, double-blind, single-dose, two-treatment, two-period, two-sequence, crossover study was conducted in 48 healthy males. In each period, a single dose of LBEC0101 or Enbrel (R) was subcutaneously injected at 25 mg and serial blood samples for PK evaluation were collected up to 648 h post-dose. Serum etanercept concentrations and anti-drug antibodies (ADA) were measured using an enzyme-linked immunosorbent assay and an affinity capture elution assay. Log-transformed maximum concentration (C-max) and area under the concentration-time curve (AUC(inf)) were compared. Tolerability was also evaluated. Results The serum concentration-time profiles were almost overlapped between LBEC0101 and Enbrel (R). Geometric mean ratio (90% confidence intervals) for C-max and AUC(inf) of LBEC0101 to Enbrel (R) were 1.02 (0.92-1.13) and 0.96 (0.87-1.05), respectively, which were within a conventional bioequivalence criteria of 0.80-1.25. ADA development was also comparable. Both drugs were well tolerated. Conclusions LBEC0101 showed similar PK, immunogenicity, and tolerability profiles to Enbrel (R) after a single subcutaneous injection in healthy males. LBEC0101 can be further developed as a potential etanercept biosimilar (ClinicalTrial.gov identifier: NCT01725620).