Heechan Lee1,2, Hyewon Chung2, SeungHwan Lee2, Howard Lee1,2, Sung Mo Yang3, Seo Hyun Yoon2, Joo-Youn Cho2, In-Jin Jang2, Kyung-Sang Yu4. 1. Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea. 2. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. 3. Biopharmaceutical Analysis, Life Science Research Institute, LG Chem R&D Campus, Daejeon, 34122, Republic of Korea. 4. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. ksyu@snu.ac.kr.
Abstract
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 (AUCinf) 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 AUCinf 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).
RCT Entities:
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 (AUCinf) 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 AUCinf 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).
Authors: Vibeke Strand; Joao Gonçalves; Timothy P Hickling; Heather E Jones; Lisa Marshall; John D Isaacs Journal: BioDrugs Date: 2020-02 Impact factor: 5.807