The results of clinical studies, in which Professor Young-Ho Kim of the Department of Internal Medicine at Sungkyunkwan University School of Medicine participated in as a corresponding author, were published in the renowned medical journal, Lancet. Lancet is one of the most prestigious medical journals in the world, which boasts its influence in the medical circle with an Impact Factor of 59.102.
The global research team led by Professor Kim first discovered that Indication extrapolation based on scientific evidence should be justified during development of biosimilars. Crohn's disease (CD) is a chronic, relapsing inflammatory disorder that predominantly affects the gastrointestinal tract. Biological therapies targeting tumour necrosis factor (TNF), a pro-inflammatory cytokine with an important role in disease pathophysiology, are an important treatment. Although TNF-targeted biological therapies have led to a paradigm shift in the clinical management of CD, their high cost might be a barrier to treatment. For this reason, biosimilar drugs with high likeness to already licensed biological therapies (originator drugs), have been developed. CT-P13 is a biosimilar version of the anti-TNF monoclonal antibody originator, infliximab. CT-P13 has been approved by the European Medicines Agency and licensed by the US Food and Drug Administration for adult and paediatric CD, adult ulcerative colitis, and all other indications of infliximab. Per regulatory guidelines, approval of CT-P13 was based on proof of biosimilarity versus infliximab in physicochemical, in-vitro, and clinical studies including randomised controlled trials (RCTs) in patients with ankylosing spondylitis or rheumatoid arthritis. Indication extrapolation is a process that allows approval of a biosimilar in a non-studied indication based on the totality of evidence from the development programme. Such extrapolation is awarded by regulatory authorities if biosimilarity has been proven and is scientifically justified. Biosimilar is the science of extrapolation. Without extrapolation of indication, there is no financial motivation for the development of biosimilars. However, concerns about extrapolation have been expressed and, to date, no RCT has compared the efficacy and safety of a biosimilar with infliximab in patients with CD.
The primary aim of this 54-week RCT, involving 220 CD patients from 58 centres in 16 countries was to demonstrate the non-inferior efficacy of CT-P13 to infliximab in terms of the proportion of patients with a decrease of 70 points or more in Crohn's Disease Activity Index (CDAI-70 response) from baseline to week 6. CDAI-70 response rates at week 6 were similar for CT-P13 and infliximab, thereby establishing non-inferiority in this study. Additionally, this study demonstrated no notable differences in the pharmacokinetics, pharmacodynamics, safety, or immunogenicity of CT-P13 and infliximab. More importantly, the study confirmed the validity of extrapolation in the development of biosimilar monoclonal antibody.
According to Professor Young-Ho Kim, "The data from our phase III study not only proves that CT-P13 is similar to infliximab, but it also provides the first scientific evidence of extrapolation. As such, we believe our pioneering study could expand global biosimilar use in the clinical setting and will continue to be cited to justify the indication extrapolation of newly developing biosimilars."