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

• Published in: The Journal of infectious diseases Vol. 227; no. 1; pp. 23 - 34
• Main Authors: Somersan-Karakaya, Selin, Mylonakis, Eleftherios, Menon, Vidya P, Wells, Jason C, Ali, Shazia, Sivapalasingam, Sumathi, Sun, Yiping, Bhore, Rafia, Mei, Jingning, Miller, Jutta, Cupelli, Lisa, Forleo-Neto, Eduardo, Hooper, Andrea T, Hamilton, Jennifer D, Pan, Cynthia, Pham, Viet, Zhao, Yuming, Hosain, Romana, Mahmood, Adnan, Davis, John D, Turner, Kenneth C, Kim, Yunji, Cook, Amanda, Kowal, Bari, Soo, Yuhwen, DiCioccio, A Thomas, Geba, Gregory P, Stahl, Neil, Lipsich, Leah, Braunstein, Ned, Herman, Gary A, Yancopoulos, George D, Weinreich, David M
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 28.12.2022
• Subjects: Clinical trials; COVID-19; COVID-19 Drug Treatment; Double-Blind Method; Hospitalization; Humans; Major; Mechanical properties; Mechanical ventilation; Monoclonal antibodies; Patients; Placebos; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; COVID-19; hospitalized; coronavirus; SARS-CoV-2; monoclonal antibody
• DOI: 10.1093/infdis/jiac320
• ISSN: 0022-1899; 1537-6613

Abstract 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. In hospitalized patients with COVID-19 on low-flow or no supplemental oxygen, casirivimab and imdevimab reduces viral load, and likely improves clinical outcomes (risk of death/mechanical ventilation, all-cause mortality), with the greatest benefit observed in seronegative patients. Lay Summary Lay Summary. Monoclonal antibody therapies that block the virus that causes COVID-19 (SARS-CoV-2) can prevent patients from being hospitalized. We hypothesized that these antibodies may also benefit patients who are already hospitalized with COVID-19. Therefore, we performed a study to determine if the monoclonal antibody combination of casirivimab and imdevimab (CAS + IMD) can decrease the amount of virus in the nose of hospitalized patients and prevent the disease from becoming more severe. The study, conducted from June 2020 to April 2021, found that CAS + IMD treatment reduced the amount of virus in these patients, and may reduce their chance of dying or needing a ventilator (a machine that helps patients breathe). Patients were examined in 2 groups: those whose immune systems, at the start of the study, had not produced their own antibodies to fight SARS-CoV-2 (seronegative patients); or those that had already produced their own antibodies (seropositive patients) at the start of the study. Seronegative patients benefited the most from CAS + IMD. No safety concerns related to CAS + IMD were observed. These results demonstrate that monoclonal antibody therapy can help hospitalized patients with COVID-19 and may decrease their chances of needing assistance to breathe or dying.