Sotrovimab, A Potential Treatment Option Non-Hospitalized High-Risk COVID Patients

Sotrovimab is an Fc-engineered human monoclonal antibody that contains the LS modification to enhance half-life and respiratory mucosal delivery. In contrast to other monoclonal antibodies, sotrovimab targets a highly conserved epitope in the SARS-CoV-2 spike protein at a region that does not compete with the binding of the angiotensin-converting enzyme 2.

To further explore, Dr Anil Gupta and his team conducted COVID-19 Monoclonal Antibody Efficacy Trial–Intent to Care Early (COMET-ICE) and evaluated the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease.

COMET-ICE is a randomized clinical trial that includes 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites. The researchers randomized 1057 patients to an intravenous infusion with 500 mg of sotrovimab (n = 528) or placebo (n = 529). The major outcome assessed was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death). They also assessed 5 secondary outcomes, tested in hierarchal order, including a composite of all-cause emergency department (ED) visit, hospitalization of any duration for acute illness management, or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation.

Key findings of the study:

Among 1057 patients randomized, the median duration of follow-up was 103 days for sotrovimab and 102 days for placebo.

♦ Upon analysis, the researchers found that all-cause hospitalization lasting longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21; absolute difference, –4.53%).

♦ They observed that four of the 5 secondary outcomes were statistically significant in favor of sotrovimab, including

• Reduced ED visit,

Hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted rr, 0.34; absolute difference, –4.91%) and

Progression to severe or critical respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR, 0.26; absolute difference, –3.97%).

They noted that the adverse events were infrequent and similar between treatment groups (22% for sotrovimab vs 23% for placebo).

The most commonly reported events were diarrhea with sotrovimab (n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%).

The authors concluded, "Among nonhospitalized patients with mild to moderate COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite endpoint of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown."

For further information:

DOI:10.1001/jama.2022.2832

Keywords: Sotrovimab, COVID-19, SARS-CoV-2 variants, nonhospitalized patients, mild to moderate COVID-19, high-risk COVID patients, JAMA, hospitalization, death,COVID-19 pneumonia,COMET-ICE trial.