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Early Treatment for COVID-19 With Neutralizing Antibody Sotrovimab
Quick Takes
- Sotrovimab, is a human monoclonal antibody that neutralizes SARS-CoV-2 and multiple other sarbecoviruses through targeting of a highly conserved epitope. It has increased half-life and improved bioavailability in the respiratory mucosa.
- A single 500 mg infusion of sotrovimab in nonhospitalized patients with COVID-19 was safe and associated with an 87% relative reduction in the risk of hospitalization within 30 days compared to placebo.
- Studies are underway to assess whether intramuscular administration of sotrovimab shows similar effectiveness.
Study Questions:
Is a single 500 mg infusion of sotrovimab in nonhospitalized patients with coronavirus disease (COVID-19) at risk for disease progression effective at reducing hospitalization or death at 30 days compared to placebo?
Methods:
This study is a prespecified interim analysis of a multicenter (37 trial sites in the United States, Canada, Brazil, and Spain), double-blind, phase 3 trial: COMET-ICE (COVID-19 Monoclonal Antibody Efficacy Trial–Intent to Care Early). The trial randomized nonhospitalized patients with symptomatic COVID-19 (≤5 days after the onset of symptoms) and at least one risk factor for disease progression (age ≥55 years, diabetes, hypertension, obesity, kidney disease, heart failure, or lung disease) in a 1:1 ratio, to receive a single infusion of sotrovimab at a dose of 500 mg or saline placebo. Patients requiring supplemental oxygen were excluded. The primary efficacy outcome was hospitalization (for >24 hours) for any cause or death within 29 days after randomization. Safety events to the infusion were ascertained.
Results:
The analysis included an intention-to-treat population of 583 patients (291 in the sotrovimab group and 292 in the placebo group). Median follow-up duration in both groups was 55 days. Demographic and clinical characteristics were similar in both groups, with 22% of patients ≥65 years old, 63% Hispanic or Latino, and 42% having two or more risk factors for progression of COVID-19 (most commonly obesity, age >55 years, and diabetes mellitus). A total of three patients (1%) in the sotrovimab group, as compared with 21 patients (7%) in the placebo group, had disease progression leading to hospitalization or death (relative risk reduction, 85%; 97.24% confidence interval, 44-96). The primary reason for the 24 hospitalizations was progressive COVID-19. In the placebo group, five patients were admitted to the intensive care unit, including one who died by day 29. Adverse events were reported by 17% of the patients in the sotrovimab group and 19% of those in the placebo group; serious adverse events were less common with sotrovimab than with placebo (in 2% and 6% of the patients, respectively).
Conclusions:
Sotrovimab reduced the risk of a composite of hospitalization or death at 30 days in nonhospitalized patients with COVID-19 without serious adverse effects.
Perspective:
Through targeting of a highly conserved epitope in the nonreceptor binding motif, sotrovimab holds the promise of neutralizing multiple sarbecoviruses, and may be an effective therapy against the inevitable future variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may extend to other viral infections. Among >1.7 million SARS-CoV-2 sequences in the Global Initiative on Sharing All Influenza Data database, amino acid positions composing the sotrovimab epitope were ≥99.8% conserved in naturally occurring viruses. One interesting pathophysiologic implication is in the fact that sotrovimab was effective, although it does not directly block the ACE2 receptor; implying other receptors have a role in the progression of disease. Findings of this first phase 3 trial in SARS-CoV-2 are promising. Even more exciting is the possibility to administer sotrovimab intramuscularly, which would allow for rapid deployment and increased access for patients with COVID-19.
Clinical Topics: COVID-19 Hub, Heart Failure and Cardiomyopathies, Prevention, Novel Agents, Acute Heart Failure, Hypertension
Keywords: Antibodies, Monoclonal, Coronavirus, COVID-19, Diabetes Mellitus, Heart Failure, Hospitalization, Hypertension, Influenza, Human, Intensive Care Units, Kidney Diseases, Obesity, Primary Prevention, Respiratory Mucosa, Risk Factors, SARS-CoV-2, Virus Diseases
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