PI-103 - EVALUATING THE CONSISTENCY AND EXTENT OF IMMUNOGENICITY REPORTING FOR RECENTLY APPROVED BIOLOGICS.

P. Simental¹, K. KOWALSKI², E. WANG³; ¹University of California, San Diego, San Diego, CA, USA, ²Pfizer, San Diego, CA, USA, ³Pfizer, New York, NY, USA.

Background: Immunogenicity (IG) can affect a biologic’s exposure, heighten safety concerns, and/or impact overall efficacy. However, IG information is inconsistently reported in USPIs with limited ability to interpret the impact of anti-drug antibodies (ADAs) to clinical outcomes. In 2014, Shankar et al. provided a framework for immunogenicity reporting in USPIs. In 2022, the FDA released a guidance on the recommended IG information to include in USPIs. We characterized IG reporting for recently approved biologics with the goal of assessing the extent the Shankar recommendations were incorporated and to determine the methods of analysis used for determining ADA impact on clinical outcomes.

Methods: 113 original drug labels approved from 2014-2022 were analyzed. FDA Clinical Pharmacology and Medical Reviews were examined for 29 of these compounds to assess how it was determined if an ADA effect on clinical outcomes existed.

Results: There were no consistent trends over time regarding ADA reporting, and though most labels report ADA incidence, there is inconsistency across further characterization. Inclusion of detailed information about ADAs and of their impact on exposure, safety, and/or efficacy trended up with higher ADA incidence. ADA impact on clinical outcomes is not reported in more than one-third of USPIs assessed. Multivariate methods were used in over half of the cases assessing impact of ADAs on exposure, whereas impact on efficacy tended to be done through a univariate assessment. The most common safety endpoints assessed were injection site reactions, hypersensitivity, and adverse events. Overall ADA status was the most frequent characteristic used in assessing clinical outcomes.

Conclusion: The new FDA labeling guidance will have high impact on label updates, as many USPIs are silent on ADA impacts to clinical outcomes.

Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm