The totality-of-the-evidence approach to the development and assessment of GP2015, a proposed etanercept biosimilar

Abstract

Objective: The aim of this review is to describe the inherent variability that is natural to biologics and, using the proposed etanercept biosimilar (GP2015) as an example, provide details on the “totality-of-the-evidence” concept, whereby all physicochemical, biologic, preclinical, and clinical data for a biosimilar and reference medicine are evaluated in an iterative, stepwise manner and shown to be highly similar.

Methods: This review was carried out by a search of published articles, reviews, abstracts and patents in PubMed/Medline and Google Scholar up to November 2016.

Results: Analytical, functional, preclinical, and clinical data provide a comprehensive understanding of both GP2015 and reference etanercept, and demonstrate a high level of similarity between the two products in accordance with regulatory requirements. The totality of the evidence from all analyses and performed trials provides a robust scientific bridge between the biosimilar and clinical experience with the reference medicine, and is used to justify the use of the biosimilar in all indications for which the reference medicine is approved.

Conclusion: Biologic therapies have revolutionized the treatment of immune-mediated inflammatory diseases. The availability of biosimilars has the potential to improve patient access to biologic medicines and stimulate innovation. Physicians may be unfamiliar with the totality-of-the-evidence concept; therefore education and information on this unique approach to developing biosimilars is required to facilitate the use of biosimilars in clinical practice and allow physicians to make informed treatment decisions.

Keywords:

• Biologic
• biosimilar
• etanercept
• GP2015
• tumor necrosis factor alpha inhibitor

Notes

Transparency

Declaration of funding

Medical writing assistance for this manuscript was paid for by Hexal AG, a Sandoz company. None of the authors received financial compensation for authoring the manuscript.

Author contributions: The authors alone are responsible for the content and writing of the paper and agree to be accountable for all aspects of the work. Employees of Sandoz who did not meet authorship criteria were responsible for reviewing the manuscript for scientific accuracy only. All authors participated in the collection, analysis and interpretation of the data, and in the writing, reviewing and approval of the final version.

Declaration of financial/other relationships

V.S. has disclosed that she has received honoraria from AbbVie, Alder, Amgen, BMS, Celgene, Genentech, Janssen, Novartis, Pfizer and UCB. G.G. has disclosed that he has received honoraria from Abbvie, Abiogen, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Galderma, Janssen, Eli Lilly, Hospira, Leo Pharma, Merck, Mundipharma, MSD, Novartis, Pierre Fabre, Pfizer Regeneron, Sandoz and Sun Pharma. M.S., R.E.M. and H.F.-Q. have disclosed that they are paid employees of Hexal AG, a Sandoz company. M.M. has disclosed that he was a paid employee of Hexal AG, a Sandoz company, at the time of manuscript preparation.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

Medical writing support was provided by Fiona Bolland, Spirit Medical Communications, funded by Hexal AG, a Sandoz company.

Notes

1 Omnitrope is a registered trade name of Sandoz GmBH, Holzkirchen, Germany

2 Inflectra is a registered trademark of Hospira, a Pfizer Company, Lake Forest, IL, USA

3 Remsima is a registered trademark of Celltrion Healthcare Co. Ltd., Incheon, South Korea

4 Benepali is a registered trade name of Biogen, Cambridge, MA, USA

5 Zarxio is a registered trade name of Sandoz Inc., Princeton, NJ, USA

6 Enbrel is a registered trade name of Amgen Inc., Thousand Oaks, CA, USA

7 Acquity is a registered trade name of Waters Corporation, MA, USA

8 Ascentis is a registered trade name of Sigma-Aldrich Company, MO, USA

9 TSKgel is a registered trade name of Tosoh Bioscience GmBH, Griesheim, Germany

10 Erelzi is a registered trademark of Sandoz GmBH, Holzkirchen, Germany

11 Amjevita is a registered trademark of Amgen Inc., Thousand Oaks, CA, USA

12 Humira is a registered trademark of AbbVie Inc., Chicago, IL, USA