Is extrapolation of the safety and efficacy data in one indication to another appropriate for biosimilars?

AAPS J. 2014 Jan;16(1):22-6. doi: 10.1208/s12248-013-9534-y. Epub 2013 Oct 11.

Abstract

CT-P13, the world's first biosimilar monoclonal antibody to infliximab, was approved for marketing in South Korea for all the six indications of infliximab, which Europe may follow, although the product was tested only in rheumatoid arthritis (RA) with a limited pharmacokinetic comparison in ankylosing spondylitis. However, the extrapolation of the efficacy and safety findings of CT-P13 in RA to the other indications appears scientifically challenging when assessed by the current regulatory requirements. RA is not a sensitive clinical model to detect potential differences between CT-P13 and infliximab, and other mechanisms of action than antagonizing tumor necrosis factor α appear to be also important, which could be different by the approved indications. Furthermore, the immunogenicity and safety profiles of CT-P13 were not sufficiently characterized in that immunogenicity potential was lowest in RA, which was even further suppressed by the concomitant use of methotrexate. Extrapolation of the safety and efficacy data in one indication to another may be inappropriate for biosimilars unless backed up by strong scientific justification, which may include the mechanistic exposure-relationship approach. Therefore, regulatory agencies need to exercise caution before granting extrapolated indications to biosimilars.

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Biosimilar Pharmaceuticals / adverse effects*
  • Drug and Narcotic Control*
  • Humans
  • Immunogenetic Phenomena
  • Infliximab
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Biosimilar Pharmaceuticals
  • CT-P13
  • Tumor Necrosis Factor-alpha
  • Infliximab