Biosimilars: Are They Bioequivalent?

Biologics have revolutionized several areas of medical therapeutics, and dozens of them are used by millions of patients. Monoclonal antibodies are only one type of biologics, but more than 900 are now in different phases of development. These drugs are complex to make and not cheap. The market is constantly increasing, and several biosimilars (copies of biologics) are being used, while many are still waiting to become available to the public. Biosimilars are more complex than generics, and regulatory agencies have very stringent criteria for approval. In the IBD field, the biosimilar infliximab (Inflectra®, Remsima®) has been recently approved by the EMA, but not by Canadian authorities. The EMA has considered that ‘high similarity' in preclinical studies together with clinical data from two trials in ankylosing spondylitis and rheumatoid arthritis warrant the ‘extrapolation' for all approved indications for original infliximab (Remicade®), specifically Crohn's disease and ulcerative colitis. Canadian authorities have not accepted extrapolation, based on differences in glycosylation (fucosylation) that could be related to properties important in Crohn's disease. Most scientific societies do support the idea of asking for specific clinical trials before approval, although they acknowledge that following EMA, FDA, and WHO guidelines warrant safe products. Practical issues such as interchangeability and substitution remain unsolved, and it is very likely that there will be different solutions at the national level. Pharmacovigilance plans will be key for obtaining reliable data. Biosimilars are not better drugs, but can be clearly cheaper and may facilitate access to new treatments in many populations.