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Extrapolation of indications for biosimilar infliximab and etanercept Posted 18/11/2016

Biosimilar infliximab (Inflectra/Remsima) was approved in Europe in September 2013 for the same indications as the originator product (Remicade). More recently, biosimilar etanercept (Benepali) was approved in Europe in January 2016 for the same indications as the originator product (Enbrel) [1]. Researchers from the National Health Service (NHS) Foundation Trust and King’s College London, discuss the extrapolation of the indications for the biosimilars [2].

According to Andrew Rutherford and James Galloway, ‘there is a subtle difference’ between biosimilar and originator infliximab. This they say is clear from a report published by the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP), which compares Remsima with the originator biological (Remicade). Although the report points out that ‘all major physicochemical characteristics and biological activities of Remsima were comparable to those of Remicade’, it also noted a reduced ability to induce cytotoxicity via a specific FC gamma pathway (FCγR111A) for CT-P13 compared to Remicade. The authors say that ‘neutralization of ligand only requires the variable region of an antibody to be present. Cytotoxicity however requires activation via the constant (FC) region of an antibody and therefore changes in FC structure could result in diminished ability to result in cytotoxicity’.

The authors believe that ‘this may be relevant in context of infliximab as the FC effector component of the monoclonal antibody may explain why the drug is effective in both inflammatory arthritis and inflammatory bowel disease. In contrast, etanercept is ineffective in inflammatory bowel disease and lacks an FC component’.

This, the authors say, is why regulatory authorities in Canada did not extrapolate the indications for biosimilar infliximab, limiting the initial approval to rheumatoid arthritis and ankylosing spondylitis. However, Health Canada has subsequently extended the approval of Inflectra to include Crohn’s disease, fistulising Crohn’s disease and ulcerative colitis.

Health Canada has also only approved biosimilar etanercept for the indications of ankylosing spondylitis and rheumatoid arthritis, despite the fact that in Europe it is also approved for the extrapolated indications of axial spondyloarthritis and plaque psoriasis [3].

EMA, and more recently the US Food and Drug Administration (FDA), according to the authors, both ‘felt that the changes were too subtle to be relevant’ and have approved both biosimilar infliximab and etanercept across all indications of the originator products [1, 4].

Conflict of interest
The authors of the research paper [2] declared that there were no conflicts of interest.

Editor’s comment
Readers interested to learn more about extrapolation of indications for biosimilars are invited to visit www.gabi-journal.net to view the following manuscripts published in GaBI Journal:

Investigating the validity of biosimilar extrapolation and interchangeability

Biosimilars: extrapolation of clinical use to other indications

GaBI Journal is indexed in Embase, Scopus, Thomson Reuters’ ESCI, and more.

If you are interested in contributing a research article in a similar area to the GaBI Journal, please send us your submission here.

Related articles
Trials for biosimilar etanercept

Trials for biosimilar infliximab

Study design for biosimilar trials

Biosimilars versus generics

Biosimilars in rheumatology

References
1. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Nov 18]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe
2. Rutherford AI, Galloway JB. Biosimilars in rheumatology: out of the laboratory and into practice. Expert Rev Clin Immunol. 2016l;12(7):697-9.
3. GaBI Online - Generics and Biosimilars Initiative. Subsequent entry biologics approved in Canada [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Nov 18]. Available from: www.gabionline.net/Biosimilars/General/Subsequent-entry-biologics-approved-in-Canada
4. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in the US [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Nov 18]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-the-US

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