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

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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).

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Acknowledgements

The authors thank all the staff members in the Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital and Seoul National University Hospital Clinical Trial Center.

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Authors and Affiliations

  1. Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea

    Heechan Lee & Howard Lee

  2. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Heechan Lee, Hyewon Chung, SeungHwan Lee, Howard Lee, Seo Hyun Yoon, Joo-Youn Cho, In-Jin Jang & Kyung-Sang Yu

  3. Biopharmaceutical Analysis, Life Science Research Institute, LG Chem R&D Campus, Daejeon, 34122, Republic of Korea

    Sung Mo Yang

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  1. Heechan Lee
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Corresponding author

Correspondence to Kyung-Sang Yu.

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Ethical standards

The study was approved by the Institutional Review Board of Seoul National University Hospital. The study was conducted in full accordance with the ethical principles of the Declaration of Helsinki and Korean Good Clinical Practices and other applicable regulations. Informed consent was obtained from all individual participants included in the study.

Competing interests

Sung Mo Yang is an employee of LG Chem, Ltd, Republic of Korea (former LG Life Sciences, Ltd), which is the sponsor and analytical institute of this clinical study. Heechan Lee, Hyewon Chung, SeungHwan Lee, Howard Lee, Seo Hyun Yoon, Joo-Youn Cho, In-Jin Jang, and Kyung-Sang Yu have no other competing interest with regard to the content of this article.

Funding

This study was funded by LG Chem, Ltd, Republic of Korea (former LG Life Sciences, Ltd).

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Lee, H., Chung, H., Lee, S. et al. LBEC0101, A Proposed Etanercept Biosimilar: Pharmacokinetics, Immunogenicity, and Tolerability Profiles Compared with a Reference Biologic Product in Healthy Male Subjects. BioDrugs 31, 349–355 (2017). https://doi.org/10.1007/s40259-017-0230-9

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  • DOI: https://doi.org/10.1007/s40259-017-0230-9

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