Anti-TNF-alpha Biosimilars Humira, Remicade and Enbrel
1st March 2012
By: Dr Daniel Galbraith, CSO,
Anti Tumor Necrosis Factor (Anti-TNF) drugs, Humira (adalimumab), Remicade (infliximab) and Enbrel (etanercept) are perhaps the most successful of all biologics both with respect to their turnover and the number of patients treated with these drugs. All have been shown in clinical trials to help with improving the clinical outcome of Rheumatoid Arthritis (RA) but each drug has to a greater or lesser extent been shown to help with other clinical indications. The mechanism of action for the treatment of RA appears to be based on the removal by the drugs of soluble TNFα (sTNFα) from the circulatory system. In the scientific literature a number of publications have indicate that the drugs all bind to the sTNFα receptors in a similar manner. The mechanisms of action of the drugs on membrane bound TNFα is known to differ between the drugs evidenced by different ADCC or CDC activity and may point to differences in the indications suitable for each drug. All of these drugs will shortly be reaching the end of their patent lifetime and a number of Biosimilar or Biobetter versions of the drug are likely to come on the market in the coming years. The question of similarity and comparability is becoming a central issue to the approval of these drugs and the important specifications for each are being closely discussed. There are some means of comparing molecules which are based on the physical characteristics: size, weight, structure but these cannot reflect their biological activity unless at a very low level. Clearly from the information already in the literature some methods are less likely to be able to discriminate between “dis-similar” molecules. Methods such as those which measure the affinity or avidity of binding such as BIACore are not shown to be discriminative between different Anti-TNFα molecules and therefore it is likely these types of test will have less emphasis placed on these by the regulatory authorities. More informative methods use the biological activity assays, these include cell migration activity, ADCC or CDC activity, cell proliferation or apoptosis measurements. The literature has clearly demonstrated that these tests will discriminate different activities between the innovator and biosimilar when performed in a controlled manner. The difficulty comes where these assays are performed without qualification or validation of the methods. These assays are known to be difficult to control because of the nature of the cells used in the assay, therefore without appropriate control and qualifications in assays there is the danger that results are less informative and ultimately will impact on product timelines and safety. The key to the success of a Biosimilar is likely to be speed to market and choosing the best means of assessing the activity of the product.