Biosimilars in Inflammatory Bowel Disease

Ready for Prime Time?

Fernando Gomollón

Disclosures

Curr Opin Gastroenterol. 2015;31(4):290-295. 

In This Article

Abstract and Introduction

Abstract

Purpose of review The goal is to review the most recent literature about biosimilars in inflammatory bowel disease (IBD), with emphasis on controversial regulatory issues.

Recent findings Although biosimilars have been in use in Europe since 2005, the recent approval of CT-P13 (Remsima, Inflectra), a biosimilar of the reference infliximab (Remicade), by the European Medicines Agency (EMA) and several regulatory agencies has become a widely discussed topic in IBD, rheumatology, and other areas. Biologics are the main drivers of cost in current IBD units, and biosimilars can reduce prices thus increasing the availability of this type of treatment. The guidelines for evaluation of biosimilars are considerably different from those of the reference biologics, regulatory agencies relying on detailed in-vitro studies for defining 'high similarity', and requiring many fewer clinical data. 'High similarity' is considered sufficient for clinical trials, as the new molecule is demonstrated so structurally similar to the reference one that no significant difference in efficacy or safety is expected. Two trials in ankylosing spondylitis and rheumatoid arthritis gave no evidence of real difference and provided the required pharmacokinetic and PD data. The main controversy remains in the 'extrapolation' of indications, accepted by EMA but not by Health Canada. Position statements from several scientific societies and some expert's reviews have expressed concerns to the concept of extrapolation without direct IBD clinical evidence, whereas EMA experts have published detailed reviews supporting extrapolation.

Summary Biosimilars in IBD are here to stay. New data are awaited to settle the controversy of extrapolation, but only the complex behavior of markets will show whether biosimilars fuel competition and extend access to biologics with significant cuts in drug costs.

Introduction

Biologics can be defined as 'a medicinal product or vaccine that consists of, or has been produced by the use of living organisms'[1] (Table 1). In fact, the mere concept of biologics is a type of 'biomimetics'[2] of which monoclonal antibodies are a paradigmatic example.[3] In the specific field of inflammatory bowel disease (IBD), infliximab was the first biologic to be used, starting with very limited indications in Crohn's disease in 1999, and in a few years becoming key in the management of both Crohn's disease and ulcerative colitis.[4] Natalizumab, adalimumab, certolizumab, golimumab, and vedolizumab followed, and more are expected in the near future.[5] Biologics are not simple to make and are costly drugs, but the global market of these products has quickly expanded in a huge business. When patents started to expire, following the old generics path,[6] copies of biologics quickly appeared and regulation was clearly needed. The name 'biosimilars' was adopted by the European Medicines Agency (EMA), as the first authority to clarify a regulatory pathway in 2005, and 16 biosimilars have been approved to date in Europe.[7,8] Biosimilar was an exotic word for the practicing IBD physician until EMA approved a biosimilar of infliximab (reference product Remicade) in 2013.[9,10] After extensive in-vitro comparative studies, and two clinical trials in ankylosing spondylitis[11] and rheumatoid arthritis,[12] EMA not only approved the new drug CT-P13 developed by Celltrion, under two brand names (Remsima and Inflectra ), but also included all the indications of Remicade in the label by simple 'extrapolation'.[9] Canadian authorities reviewed the same data, and approved the biosimilar but only for clinically tested indications and psoriasis.[13] The Food and Drug Administration (FDA) path to biosimilars is clearly slower,[14] but in 7 January 2015, the first biosimilar, a filgastrim, was approved after an application from a world leading company in the field,[15] suggesting that biosimilars will be reaching also the U.S. market in the next years.

A word of caution is mandatory in this topic. Biosimilars being a multimillion dollar business,[16] different points of view can be easily biased by personal and/or corporative interests: a very critical approach is needed. There are several controversial issues: regulation, extrapolation, interchangeability, and product naming being some examples. As we are reviewing only some of the reports published in the last year, we recommend to the reader some recent reviews[1,9,13,17,18,19–22] and more specific publications on interchangeability,[23] terminology,[24] or product identification[25] for a more balanced view. We will start with costs and physicians' views to examine more in detail the most controversial issue of extrapolation, and finally give a response to this article title's question.

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