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 ® , 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 ® 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 ® . Geometric mean ratio (90% confidence intervals) for C max and AUC inf of LBEC0101 to Enbrel ® 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 ® after a single subcutaneous injection in healthy males. LBEC0101 can be further developed as a potential etanercept biosimilar (ClinicalTrial.gov identifier: NCT01725620).