Casirivimab and Imdevimab for the Treatment of Hospitalized Patients With COVID-19.

Background: The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD).
Methods: In this phase 1/2/3, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4 g or 8.0 g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus.
Results: In total, 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was -0.28 log10 copies/mL (95% confidence interval [CI], -.51 to -.05; P = .0172). The primary clinical analysis of death or mechanical ventilation from day 6 to 29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2%-74.0%). No safety concerns were noted.
Conclusions: In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients.
Clinical Trials Registration: NCT04426695.
Competing Interests: Potential conflicts of interest. S. S.-K., S. A., Y. Sun, R. B., J. Mei, J. Miller, E. F.-N., C. P., V. P., Y. Z., A. M., J. D. D., Y. K., A. C., B. K., Y. Soo, A. T. D., G. P. G., L. L., N. B., and D. M. W. are employees/stockholders of Regeneron Pharmaceuticals, Inc, and report grants from Biomedical Advanced Research and Development Authority (BARDA). E. M. reports payments to his institution received from National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases, NIH/National Institute of General Medical Sciences, SciClone Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Pfizer, Chemic Labs/KODA Therapeutics, Cidara, and Leidos Biomedical Research Inc/NCI. V. P. M. and J. C. W. report grants from BARDA. S. S. is an Excision BioTherapeutics employee/stockholder and former Regeneron Pharmaceuticals, Inc, employee and current stockholder, and reports grants from BARDA. L. C. is a Regeneron Pharmaceuticals, Inc employee and reports grants from BARDA. A. T. H. is a Regeneron Pharmaceuticals, Inc employee/stockholder, a former Pfizer employee and current stockholder, has a patent pending with Regeneron Pharmaceuticals, Inc and reports grants from BARDA. J. D. H., K. C. T., and G. A. H. are employees/stockholders of Regeneron Pharmaceuticals, Inc and have a patent pending, which has been licensed and receiving royalties, with Regeneron Pharmaceuticals, Inc. R. H. is a former employee and current stockholder of Regeneron Pharmaceuticals, Inc, and reports grants from BARDA. N. S. and G. D. Y. are employees/stockholders of Regeneron Pharmaceuticals, Inc, and have issued patents (US Patent Nos. 10 787 501, 10 954 289, and 10 975 139) and pending patents, which have been licensed and receiving royalties, with Regeneron Pharmaceuticals, Inc, and reports grants from BARDA. Funding to pay the Open Access publication charges for this article was provided by Regeneron Pharmaceuticals, Inc.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)