Analytical Data and Single-Dose PK are Sufficient to Conclude Comparable Immunogenicity for Biosimilars: An Ustekinumab Case Study.

Comparative immunogenicity is a key regulatory requirement for biosimilars. In a streamlined biosimilar development process, absent a comparative clinical efficacy study, the analytical data and clinical pharmacokinetics (PK) study need to provide sufficient evidence for a conclusion of comparable immunogenicity. In this case study, we have reviewed the role of analytical and clinical data in the immunogenicity assessment of all currently available ustekinumab biosimilars and their reference product. Public information for European Medicines Agency-and US Food and Drug Administration-approved biosimilars reveal that the single-dose clinical PK studies were sensitive in detecting differences in terms of immunogenicity between the biosimilar and the reference product, a finding that was replicated in the comparative clinical efficacy studies. The rates for anti-drug antibodies and neutralizing antibodies were comparable albeit numerically lower for all biosimilars compared to their reference product, which correlates with lower levels of non-human glycans such as α-1,3 galactose known to be potentially relevant for immunogenicity. Our study demonstrates that the single-dose clinical PK studies were sensitive in confirming comparable immunogenicity of ustekinumab biosimilars with their reference product. The comparative clinical efficacy studies revealed no additional information. This finding adds on to the evidence that clinical PK and the comparative analytical assessment, specifically the comparison of quality attributes with potential immunogenic relevance, suffice for the evaluation of immunogenicity of biosimilars in general.