Abstract
[Introduction] Clinical consequences, such as decreased systemic exposure, reduced efficacy or onset of an adverse events, induced by anti-drug antibodies (ADA) are observed even now fully human antibody has been developed. T cell assay using human PBMCs is known as a typical assay for estimating immunogenicity and the results of the T cell assay are considered to correlate with the clinical ADA formation rate. However, even when ADA is observed in humans, clinical consequences are not always occurred. In this study, we investigated the relationship among clinical ADA formation rate, the results of T cell assay and clinical consequences mainly for the antibody drugs on the market.
[Methods] A total of 37 antibodies, including Bococizumab as an antibody whose development was discontinued due to ADA formation in clinical trials, were investigated. We mainly investigated the initial assessment report of PMDA and classified the presence or absence of clinical consequences induced by ADA into Yes / No. For the positive rate of T cell assay, public information was referred.
[Results] It was difficult to estimate the presence or absence of clinical consequences from the clinical ADA formation rate. The correlation between the clinical ADA formation rate and the positive rate of T cell assay was clearly observed. In addition, there was no clear difference in ADA formation rate and clinical consequences depending on the antibody type (Chimeric, humanized or fully human antibodies). Decreased systemic exposure was the most frequently observed among the clinical consequences.
