LB-009 - IMPACT OF INTRAMUSCULAR INJECTION SITE ON SOTROVIMAB PHARMACOKINETICS.
Thursday, March 23, 2023
5:00 PM – 6:30 PM EDT
A. El-Zailik1, J. Sager1, J. Moore2, S. Parra1, Y. Sanchez-Pearson2, P. Sarkar3, A. Aylott4, A. Nader5, M. Aldinger1, A. Skingsley2, E. Mogalian1, C. Garner1, M. Reyes1; 1Vir Biotechnology, San Francisco, CA, United States, 2GSK, Brentford, United Kingdom, 3GSK, Bengaluru, India, 4GSK, Stevenage, United Kingdom, 5GSK, Upper Providence, PA, United States.
Clinical Pharmacologist Vir Biotechnology San Francisco, California, United States
Background: Sotrovimab, a dual-action Fc-engineered human immunoglobulin G (IgG1) mAb, binds to a conserved epitope on the SARS-CoV-2 receptor binding domain and was developed to treat mild to moderate COVID-19. A high concentration formulation is being evaluated to offer the potential for IM administration at lower volumes and at different injection sites.
Methods: COSMIC (NCT05280717) is a phase I, open label healthy volunteer study comprising three parts. Part A is an ongoing randomized, parallel group study investigating the relative bioavailability, safety and tolerability of two concentrations of sotrovimab administered at different injection sites. 215 subjects were randomized in a 2:2:1:1 ratio into four treatment arms: dorsogluteal injection (62.5 mg/mL), or 100 mg/mL administered as dorsogluteal, thigh or deltoid injection(s). PK will be evaluated for 24 weeks post-dose.
Results: Preliminary PK is available from 50 participants who received a 500 mg IM dose of sotrovimab of the higher concentration (100 mg/mL). Administration into thigh or deltoid resulted in higher geometric mean Cmax and AUCD1-15 and lower inter-subject variability compared to 100 mg/mL dorsogluteal. Following gluteal, thigh or deltoid injections, the geometric mean (%CV) Cmax was 44.8 µg/mL (63.3), 70.9 µg/mL (35.5) and 65.1 µg/mL (27.1), respectively, and the geometric mean (%CV) AUCD1-15 was 534 day*µg/mL (67.5), 814 day*µg/mL (39.7) and 782 day*µg/mL (26.3), respectively. Median Tmax was earlier following thigh (4 days) and deltoid (5.5 days) injection than gluteal (7 days) injection.
Conclusion: Administration of sotrovimab into thigh or deltoid muscles may improve exposure and reduce inter-subject variability compared to gluteal IM administration. These data may inform IM injection site selection for mAbs.
