Biosimilars in inflammatory bowel disease: ready for prime time?

Abstract

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