PII-001 - COMPARISON OF THE IMMUNOGENICITY RISK OF BIOTHERAPEUTICS ADMINISTERED VIA INTRAVENOUS VS. SUBCUTANEOUS ROUTE OF ADMINISTRATION.

J. Felderman¹, D. Potter², L. Ramaiah³, M. Vazquez-Abad², D. Messing², Y. Chen⁴; ¹University of California, San Diego, La Jolla, CA, USA, ²Pfizer, Cambridge, MA, USA, ³Pfizer, Pearl River, NY, USA, ⁴Pfizer, La Jolla, CA, USA.

Background: There is a notion that subcutaneous (SC) route of administration (RoA) increases the risk of immunogenicity compared with intravenous (IV) RoA of biotherapeutics. However, there is a lack of systematic evaluations on clinical data to support this claim. This analysis aimed to compare the immunogenicity risk of the same biotherapeutics administered via IV and SC RoA.

Methods: Anti-drug antibody (ADA) data published from 4 biotherapeutic products spanning 4 studies with IV and SC RoA in a total of 31 treatment groups were analyzed. The RoA is the primary independent variable of interest while biotherapeutic product, adjusted dose, and ADA sampling schedule were selected as controlling variables. Analysis of variance models were used to compare the ADA incidence between IV and SC RoA, while accounting for controlling variables and potential statistical interactions. Finally, published ADA data from 10 additional approved biotherapeutic products, with IV and SC RoA, were pooled with the initial ADA data and evaluated for immunogenicity risk.

Results: RoA had no significant effect on ADA incidence for the initial ADA dataset (p-value = 0.88). The single variable that had a significant effect on the ADA incidence was the biotherapeutic product. None of the other controlling variables, including their interactions with RoA, were significant. When all published ADA data from the 14 products were pooled, there was no significant effect of RoA on ADA incidence (p-value = 0.98).

Conclusion: There appears to be no significant difference in immunogenicity risk associated with SC RoA when compared with IV RoA, based on the present analyses of ADA data from 14 biotherapeutic products.

Shankar G, Arkin S, Cocea L, et al. Assessment and reporting of the clinical immunogenicity of therapeutic proteins and peptides – harmonized terminology and tactical recommendations. AAPS J. 2014; 16(4):658-673.