Impact Of Immunogenicity On Efficacy And Safety Of Biosimilars – Importance Of ADA And nAb Testing During The Clinical Development

Prepared By Adam Tuszyner

The presence of anti-drug antibodies (ADAs) poses a notable concern for the efficacy and safety of biotherapeutics, potentially leading to diminished pharmacological activity and acute adverse reactions. Notably, higher immunogenicity in a candidate biosimilar product indicates significant quality disparities, underscoring the importance of immunogenicity comparison in biosimilar drug development, irrespective of its relevance for the reference molecule.

Despite recent calls to curtail clinical testing of biosimilars, regulatory bodies like the EMA and FDA uphold the necessity for thorough immunogenicity evaluation, suggesting this requirement will persist. All protein-based therapeutics inherently provoke some degree of immune response, ranging from negligible rates for certain drugs like canakinumab to substantially higher rates, such as 40% observed with infliximab.

Learn more about why the impact of ADAs on pharmacokinetics, efficacy, and safety is particularly notable for therapeutics capable of binding to the complementarity-determining region (CDR) and neutralizing their activity (nAbs).