The monoclonal antibody sotrovimab reduced the risk of hospitalization or death by 85% in high-risk patients with mild-to-moderate COVID-19.
Sotrovimab (formerly VIR-7831) is a pan-sarbecovirus monoclonal antibody designed to prevent the progression of COVID-19 disease in high-risk patients. A recent study published in The New England Journal of Medicine theorized that a monoclonal antibody that neutralizes all sarbecoviruses would target a highly conserved epitope that would remain effective as COVID-19 mutates.
Sotrovimab contains a two–amino acid Fc modification that increase half-life and may improve bioavailability in the respiratory mucosa by enhanced engagement with the neonatal Fc receptor. The modification may permit therapeutic concentrations for longer durations, potentially resulting in immune-mediated viral clearance.
In the phase 3, multicenter, double-blind, placebo-controlled study, COVID-19 Monoclonal Antibody Efficacy Trial–Intent to Care Early (COMET-ICE), investigators evaluated a single intravenous infusion of 500 mg of sotrovimab for preventing mild-to-moderate COVID-19 in high-risk, non-hospitalized patients. Patients were recruited in the US, Canada, Spain, and Brazil and followed from August 27, 2020 through March 4, 2021.
Eligible adult patients PCR-tested positive and were symptomatic for COVID-19. Patients were high-risk for developing severe COVID-19 due to age (55 years of age or older) or because they fulfilled one or more risk factors, including diabetes, obesity, chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate-to-severe asthma.
Patients were randomly assigned 1:1 to receive either a single 500 mg, 1-hour infusion of sotrovimab, or a saline placebo. The primary outcome was the percentage of patients who died or were hospitalized for more than 24 hours. By January 19, 2021, 583 patients were assigned either sotrovimab (291 patients) or placebo (292 patients). The average duration of follow-up in the intention-to treat population was 72 days for the sotrovimab and placebo groups.
Overall, 1% (3/291) of patients in the sotrovimab group and 7% (21/292) patients in the placebo group had disease progression requiring hospitalization or death. Notably, the 1 hospitalized patient in the sotrovimab group had a medical history of small-intestinal obstruction. Emergency department visits for fewer than 24 hours occurred more frequently in the placebo group, and all 5 patients admitted to the ICU were in the placebo group.
Serious adverse events, most of which were hospitalizations for COVID-19–related causes, occurred in 2% of patients in the sotrovimab group and 6% of patients in the placebo group. No serious adverse events were considered by the investigators to be related to sotrovimab. One patient in the placebo group died from COVID-19 pneumonia on day 37.
A single 500 mg dose of sotrovimab was found to reduce the risk of hospitalization or death by 85% in high-risk adults with symptomatic COVID-19. Investigators saw the success of COMET-ICE as indicative of sotrovimab’s ability to neutralize COVID-19 and its current and subsequent variants.