Sotrovimab may reduce COVID-19 disease progression

The pan-sarbecovirus monoclonal antibody sotrovimab appears to reduce the risk of COVID-19 disease progression in high-risk patients, according to interim results of the phase III COMET-ICE* trial.

This ongoing, multicentre trial involved 583 non-hospitalized adults (intention-to-treat population; randomized until January 19, 2021; median age 53 years, 46 percent male) with symptomatic, mild-to-moderate PCR- or antigen test-positive COVID-19 (≤5 days after symptom onset) and ≥1 risk factor for disease progression**. They were randomized 1:1 to receive a single sotrovimab infusion (500 mg) or placebo, in addition to local standard of care.

Twenty-two percent of patients were aged ≥65 years and 42 percent had ≥2 risk factors for progression. The median BMI was 32.1 kg/m². Fifty-eight percent of patients had symptoms for ≤3 days. The most common COVID-19 symptoms were cough, muscle aches or myalgia, headache, and fatigue.

Within 29 days of randomization, disease progression leading to any-cause hospitalization (for >24 hours) or death occurred in fewer patients in the sotrovimab compared with placebo group (1 percent vs 7 percent [n=3 vs 21]), which translated to an 85 percent relative risk reduction (97.24 confidence interval, 44–96 percent; p=0.002). [N Engl J Med 2021;doi:10.1056/NEJMoa2107934]

Twenty-three of the hospitalizations occurred due to COVID-19 progression. One sotrovimab recipient with a history of small-intestinal obstruction was hospitalized for that reason.

Five patients in the placebo group required intensive care unit (ICU) admission, one of whom died by day 29. None of the sotrovimab recipients required ICU admission.

“[T]his finding suggests that sotrovimab prevented more severe complications of COVID-19 in addition to preventing hospitalization,” the authors said.

Fewer patients in the sotrovimab than placebo group presented at the emergency department (without hospitalization or for <24 hours; n=3 vs 7).

Among the 868 patients included in the safety assessment (randomized until February 17, 2021), adverse events (AEs) occurred in a comparable proportion of sotrovimab and placebo recipients (17 percent vs 19 percent). However, grade 3–4 and serious AEs occurred in fewer sotrovimab than placebo recipients (2 percent vs 6 percent for both grade 3–4 and serious AEs). The most common AE (≥1 percent) in the sotrovimab group was diarrhoea, which occurred in six sotrovimab and three placebo recipients. Infusion-related reactions occurred in 1 percent of each group. Two deaths occurred in the placebo group, one before and one after day 29.

“There was … no evidence of antibody-dependent enhancement with sotrovimab,” the authors pointed out.

Despite the development of effective vaccines, treatment of COVID-19 remains an unmet clinical need, said the authors. Issues with vaccine access, contraindications, lack of response to vaccine, and the emergence of variant viruses are among the challenges still being faced. “[These] may all contribute to what is likely to be a large and enduring number of patients with COVID-19 for whom treatment is warranted,” they added.

“Treatments for COVID-19 that retain activity even in the face of a rapidly evolving virus are needed … The results of this interim analysis of COMET-ICE indicate that sotrovimab can be a therapeutic agent for outpatients with COVID-19,” they concluded.

The authors noted that the small number of hospitalizations in the sotrovimab group precluded determination of characteristics that may be tied to sotrovimab treatment failure. Furthermore, it is yet unknown how emerging autologous immunity may impact the effects of sotrovimab.