Variability of Biologics and its Impact on Biosimilar Development

Abstract

This symposium took place during the International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland, June 2019, and focussed on scientific aspects associated with development and approval of rituximab biosimilars in lymphoma. The symposium began with an overview presented by Dr Cornes detailing the urgent economic need for biosimilars to improve access to these biologic treatments in oncology and other therapy areas. Prof Schellekens, author of the first paper on biosimilars in 2002, discussed how regulatory strategies for biosimilars were shaped, and how these have evolved in the intervening years. Today, the emphasis of biosimilar development is placed on extensive analytical testing to demonstrate a match with the reference medicine at a fundamental level. Clinical testing plays a confirmatory role, removing any residual uncertainty regarding potential clinical differences between biosimilar and reference medicine. Dr Schiestl presented further detail on analytical perspectives on biosimilars. Development of biosimilars is complicated by the inherent variability of biological synthesis techniques employed in the manufacture of biologics. This variability is further increased by ongoing changes to manufacturing processes, which can result in changes in biological activity. Consistent quality is therefore a cornerstone of biosimilar development. Prof Jurczak provided a comprehensive overview of the factors that must be considered during clinical development of a biosimilar. Clinical trials for biosimilars have a confirmatory role in the development process, rather than the pivotal role played by clinical trials for reference medicines. Therefore, these trials have markedly different objectives compared with reference clinical trials, resulting in differences in the chosen endpoints. In biosimilar trials, response endpoints, which provide rapid and sensitive assessments of equivalence, are preferred to survival endpoints, which require large and lengthy trials for adequate evaluation. Prof Jurczak illustrated this using data from the Phase III clinical trials of the Sandoz rituximab biosimilar. In this trial, Sandoz rituximab demonstrated an equivalent response rate to reference rituximab. Increasing economic pressure on healthcare systems means that biosimilars are likely to play an increasing role in the treatment of cancer in coming years, requiring clinicians to increase their familiarity with these important medicines.