Characterization and non-clinical assessment of the proposed etanercept biosimilar GP2015 with originator etanercept (Enbrel^®)

ABSTRACT

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®).

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-α, 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-α, 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.

KEYWORDS:

• TNF-α
• biosimilars
• disease-modifying drugs
• etanercept
• GP2015
• Enbrel

Acknowledgments

Editorial assistance was kindly provided by Dr Peter Weber and Dr Steve Clissold of ContentEdNet, Germany. The authors acknowledge the role of BioMedCode relating to studies involving the human Tg197 TNF transgenic mouse model of polyarthritis in identifying sensitive study designs to optimally address efficacy comparability in this well-establish and characterized disease model.

Declaration of interest

The authors are all paid employees of either Sandoz Biopharmaceuticals/Hexal AG, Holzkirchen, Germany, Hexal AG Oberhaching or Novartis Pharma AG, Basel, Switzerland. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized in the production of this manuscript and funded by Sandoz Biopharmaceuticals/Hexal AG, and Novartis Pharma AG.

Additional information

Funding

This work was sponsored and carried out internally at Sandoz Pharmaceuticals and Novartis.