PII-017 - REVIEW OF BISPECIFIC ANTIBODIES’ IMMUNOGENICITY IN CLINICAL DEVELOPMENT.

Z. Zheng^1,2, C. Chen³, S. Ren¹, A. Phipps⁴, K. Lim¹, X. Song¹; ¹AstraZeneca, Gaithersburg, MD, USA, ²University of Houston, Houston, TX, USA, ³AstraZeneca, South San Francisco, CA, USA, ⁴AstraZeneca, Cambridge, United Kingdom.

Background: Bispecific antibodies (BsAbs) have acquired much attention as the next-generation strategy of the treatment for diseases. A large proportion of BsAbs entering early clinical development often show immunogenicity, potentially impacting both the safety and efficacy of the treatment. Therefore, it is vital to assess potential factors and clinical consequences of immunogenicity. The objective was to conduct a literature review of clinical trials on BsAbs for the detection of and clinical consequences related to the development of unwanted immune response to the immunotherapy.

Methods: The development status of bispecific antibodies were searched from Drugs@FDA, EMA website and Clinicaltrials.gov with the keywords of “bispecific” and “bispecific antibodies”. Immunogenicity results were collected from published papers and conference abstracts.

Results: Until July 20, 2022, results of 7 approved BsAbs and more than 200 BsAbs in clinical development are summarized. About 90% of these BsAbs are developed for cancer treatment. Target, route of administration, origin of antibodies, and patient status’ impact on immunogenicity were analyzed. The analysis of the data revealed that 1) these factors might affect immunogenicity all together. 2) specificity, sensitivity, drug tolerance and precision of the anti-drug antibody assay might also affect the result. 3) immunogenicity might further affect the BsAbs’ pharmacokinetics, pharmacodynamics, efficacy or safety.

Conclusion: When evaluating one drug candidate’s immunogenicity in clinical development, the totality of the data needs to be considered. Continued research of the immunogenicity issue could pave the way for addressing immunogenicity of BsAbs in a standardized manner and maximize probability of clinical success.