Comparative Assessment of Immunogenicity Profiles: A Crucial Factor in Biosimilar Development

Comparing the immunogenicity profiles of biosimilars and their reference biologics reveals minimal differences in anti-drug antibody and neutralizing antibody incidences. It suggests further investigation to inform cost-effective biosimilar development strategies, according to research published online ahead of print in Clinical Pharmacy & Therapeutics.  

Immunogenicity is a crucial factor in the development of biologics, but reference biologics labeling documents often fail to address immunogenicity impact and make the development of biosimilars more difficult. A study compared the immunogenicity profiles of biosimilars and their reference biologics in review reports from the Center for Drug Evaluation and Research (CDER) and the US Food and Drug Administration (FDA) to address this issue. The analysis included 22 applications approved between April 5, 2016, and December 17, 2021. 

Most differences in anti-drug antibody (ADA) and neutralizing antibody (NAb) incidences between biosimilars and reference products were within ± 15% and ± 20%, respectively, with a few exceptions. Immunosuppressants had higher ADA-positive and NAb-positive subjects than antineoplastic agents, and the differences in incidence were broader. Biosimilars showed consistency with their reference products in terms of pharmacokinetic parameters, and no increase in immunogenicity was found in switching studies. The majority of biosimilars had post-marketing requirements unrelated to immunogenicity concerns. 

“The FDA considered the totality of evidence assessing clinical consequences of immunogenicity differences, if any,” said researchers. “Additional information on titers and subgroup analysis may be warranted to elucidate the critical attributes of immunogenicity impact and to aid in forming cost-effective strategies for biosimilar development.” 

Reference  

Cheng CA, Jiang AL, Liu YR, et al. Investigation of immunogenicity assessment of biosimilar monoclonal antibodies in the United States. Clin Pharmacol Ther. Printed online ahead of print August 27, 2023. doi.org/10.1002/cpt.3033