Pharmacokinetic Comparability Assessment of Tixagevimab and Cilgavimab Developed for COVID-19 Prevention and Treatment Using Standard Exposure Metrics and Partial Area Under the Curve

BACKGROUND AND OBJECTIVE: AZD7442 is a combination of extended half-life monoclonal antibodies (mAbs; tixagevimab and cilgavimab), developed to neutralize SARS-CoV-2. This open-label Phase 1 study compared pharmacokinetics (PK) of three AZD7442 formulations in which component mAbs were (1) co-formulated versus separately formulated and (2) derived from clonal cell line or cell pool material when separately formulated. METHODS: ) were used for PK comparability assessment between treatments (A vs B, B vs C and A vs C). A post hoc analysis using partial area under the curve (pAUC) was also conducted. RESULTS: GMR (0.7933) was slightly below the pre-defined threshold of 0.8000. Low immunogenicity and acceptable safety profiles were observed across treatments. CONCLUSIONS: Pharmacokinetic comparability of tixagevimab, cilgavimab and AZD7442 was demonstrated between the different treatments based on analyses using traditional bioequivalence metrics or pAUCs. Partial AUC could serve as an exposure metric when evaluating PK comparability for extended half-life mAbs. TRIAL REGISTRY: Clinical trials registration number: ClinicalTrials.gov NCT05166421.