Biosimilar monoclonal antibodies: the scientific basis for extrapolation

Abstract

Introduction: Biosimilars are biologic products that receive authorization based on an abbreviated regulatory application containing comparative quality and nonclinical and clinical data that demonstrate similarity to a licensed biologic product. Extrapolation of safety and efficacy has emerged as an important way to simplify biosimilar development. Regulatory authorities have generally reached the consensus that extrapolation of similarity from one indication to other approved indications of the reference product can be permitted if it is scientifically justified.

Areas covered: Recently, the first biosimilar, biosimilar infliximab (Remsima/Inflectra) to the innovator monoclonal antibody infliximab (Remicade), was approved in the European Union, Canada and South Korea; the USA subsequently approved its first biosimilar, a less complex molecule (filgrastim-sndz). Based on two clinical trials of biosimilar infliximab in patients with rheumatoid arthritis and ankylosing spondylitis, the European Medicines Agency allowed extrapolation to all eight approved indications for innovator infliximab, whereas Health Canada did not permit extrapolation to the indications for ulcerative colitis and Crohn’s disease. These differing decisions on extrapolation of indications for biosimilar infliximab highlight important unanswered regulatory and scientific questions. Here, we propose substantive scientific considerations for indication extrapolation.

Expert opinion: The preclinical and clinical criteria that are currently required to merit indication extrapolation have not been rigorously evaluated.

Keywords:

• biosimilars
• extrapolation
• infliximab
• monoclonal antibodies
• TNF inhibitors

Acknowledgements

The authors would like to thank P Tebbey and E Alexander from AbbVie for critical review of the manuscript.

Declaration of interest

Medical writing support was provided by M Mikesell of Complete Publication Solutions, LLC; this support was funded by AbbVie Inc. H Schellekens has served and is currently serving on advisory boards and safety monitoring boards of producers of biosimilar and reference products, and he has participated in publications and meetings sponsored by the pharmaceutical industry. F Faccin receives a salary as an employee of AbbVie Inc. and may also receive AbbVie Inc. stock and stock units. J Venema received a salary as an employee of AbbVie Inc. and may also have received AbbVie Inc. stock and stock units. E Lietzan was previously counsel for AbbVie Inc. (as a partner at Covington & Burling LLP) and is currently retained by AbbVie Inc. as a regulatory consultant. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

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