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SP0027 Biosimilars: Potential Clinical Differences and European Regulatory Aspects
  1. J.V. Esplugues Mota1,2,3
  1. 1CIBERehd
  2. 2FISABIO-Hospital Universitario Dr. Peset
  3. 3Department of Pharmacology, University of Valencia, Valencia, Spain

Abstract

Although successful drugs, the use of anti-TNFs is limited by their high cost, and in the present climate of economic difficulty, there is pressure to find alternatives that reproduce their effects at a lower price. Due to their large molecular size and structural complexity, anti-TNFs are impossible to duplicate, unlike smaller, chemically-generated compounds, which can be copied. However, unlike generics, biosimilars are similar rather than identical to the original drugs. Determining the level of similarity that guarantees a comparable efficacy and safety represents a new test for the pharmacological market. Biosimilars of smaller biological molecules, such as somatotropin, EPO and GCSF (granulocyte colony-stimulating factor), are already commercially available, but are less of a challenge than anti-TNF a biosimilars, which are 3-4 times larger. The European Medicines Agency has recently approved the first infliximab biosimilar, which has already been marketed in various European countries with all the indications for which the original product was approved. However, last January, the Canadian Agency for Drug and Technologies in Health ruled out the use of this biosimilar to treat inflammatory bowel disease in adult and paediatric patients. The fact that two such important regulatory agencies have published contrasting rulings based on the same data is testimony to the complexity of these large protein molecules. Indeed, the novel pharmacology of biosimilars has forced regulatory authorities to develop specific guidelines for their development. European regulations require manufacturers to validate the synthesis process through which they create biosimilars, since the process employed to create the original drug cannot be reproduced. In addition, they are required, not only to carry out pharmacokinetic studies, but also to compare biosimilars with the original product in phase I and II clinical trials. In the case of the infliximab biosimilar, its approval has been achieved through two clinical trials involving a total of 860 patients; a therapeutic equivalence study with rheumatoid arthritis subjects and a pharmacokinetic study with ankylosing spondylitis subjects. No significant differences were detected with respect to infliximab in either study. Specific immunogenicity studies are also required, as well as a specific pharmacovigilance plan that should continue for some time after the drug is made commercially available. This caution is merited by the potential antigenicity of biosimilar proteins, and is of particular relevance in the case of infliximab, which has the most antigenic profile of all the anti-TNFs currently on the market. Given that the infliximab biosimilar is the first of its class, only time will tell whether it can influence the treatment of rheumatologic diseases, in which infliximab is not currently a first-line option.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.6337

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