Characterization and non-clinical assessment of the proposed etanercept biosimilar GP2015 with originator etanercept (Enbrel®)
Characterization and non-clinical assessment of the proposed etanercept biosimilar GP2015 with originator etanercept (Enbrel®)
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DOI：
10.1080/14712598.2016.1217329
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发表时间：
2016-10-01
影响因子：
4.6
通讯作者：
Da Silva, Antonio
中科院分区：
文献类型：
--
作者：
Hofmann, Hans-Peter;Kronthaler, Ulrich;Da Silva, Antonio
背景和目标：生物仿制药是经批准的生物制剂，在质量、安全性和功效方面与原研产品相当。在此，作者描述了旨在确定 GP2015 和原研药依那西普 (Enbrel (R)) 生物相似性的功能性和非临床研究。方法：Enbrel 生物仿制药 (GP2015) 的开发涉及原研药的广泛表征。采用了涉及最先进的功能表征研究和非临床评估（药代动力学、药效学和安全性/毒理学）的逐步目标导向和迭代技术开发计划，旨在确认 GP2015 在非临床水平上与原研药（Enbrel）相当。 结果：在体外测试中，GP2015 和 Enbrel 对 TNF-α 具有相当的结合亲和力， C1q 补体和完整的 Fc 受体组。全面的功能表征测试证实了 GP2015 与 Enbrel 在结合和中和 TNF-α 的能力方面具有可比性，这反映了依那西普的主要作用机制。非临床数据证实，拟议的 Enbrel 生物仿制药 GP2015 在其药代动力学特性、药效活性、功效以及安全性/毒性方面具有可比性。结论：在旨在确认生物相似性的研究中，拟议的 Enbrel 生物仿制药 GP2015 被证明与其原研产品具有可比性。
Background and objective: Biosimilars are approved biologics that are comparable to an originator product with respect to quality, safety and efficacy. Herein, the authors describe the functional and non clinical studies designed to determine the biosimilarity of GP2015 and originator etanercept (Enbrel (R)).Methods: The development of an Enbrel biosimilar (GP2015) involved extensive characterization of the originator. A step-wise target-directed and iterative technical development program involving state-of-the-art functional characterization studies and non-clinical evaluations (pharmacokinetics, pharmacodynamics and safety/toxicology) was applied with the aim of confirming that GP2015 is comparable to originator (Enbrel) at the non-clinical level.Results: In in vitro tests, GP2015 and Enbrel had comparable binding affinities to TNF-alpha, C1q complement and a complete panel of Fc-Receptors. Comprehensive functional characterization testing confirmed the comparability of GP2015 with Enbrel in terms of its ability to bind to and neutralize TNF-alpha, which reflects the primary mechanism of action of etanercept. Non-clinical data confirmed that the proposed biosimilar to Enbrel, GP2015, is comparable with regards to its pharmacokinetic properties and pharmacodynamic activity, and efficacy as well as safety/toxicity.Conclusion: The proposed Enbrel biosimilar, GP2015, was shown to be comparable to its originator product in studies designed to confirm biosimilarity.