Posted by Carla Rothaus
In the trial by Gupta et al., did sotrovimab administered early in the disease course prevent progression of Covid-19 in high-risk patients?
Gupta et al. recently reported the results of a prespecified interim analysis of a trial designed to evaluate the efficacy and safety of sotrovimab in high-risk, ambulatory patients with mild-to-moderate Covid-19. Read the NEJM Original Article here.
Q: What kind of therapeutic agent against SARS-CoV-2 might remain effective even as new variants emerge?
A: Highly effective therapeutic agents directed against SARS-CoV-2, the virus that causes Covid-19, are needed for high-risk persons. Recent data suggest that one option is monoclonal antibody therapy, which can reduce the risk of hospitalization; however, the emergence and proliferation of SARS-CoV-2 variants that confer resistance to some antibodies are troubling. Furthermore, because additional variants of concern will probably continue to emerge, there is a great unmet need for therapeutic agents that, alone or in combination, can remain effective as the virus evolves. One possible solution is a monoclonal antibody that neutralizes SARS-CoV-2 by targeting an evolutionarily conserved epitope that lies outside the rapidly evolving receptor-binding motif.
Q: What is sotrovimab?
A: Sotrovimab is an engineered human monoclonal antibody that neutralizes SARS-CoV-2 and multiple other sarbecoviruses, including SARS-CoV-1, the virus responsible for the SARS outbreak two decades ago. In fact, the parental form of sotrovimab, S309, was isolated from a patient with SARS-CoV-1. Gupta et al. hypothesized that a monoclonal antibody that neutralizes all sarbecoviruses would target a highly conserved epitope that would be functionally retained as SARS-CoV-2 evolves.
Morning Report Questions
Q: In the trial by Gupta et al., did sotrovimab administered early in the disease course prevent progression of Covid-19 in high-risk patients?
A: The results of this interim analysis indicate that sotrovimab can be a therapeutic agent for outpatients with Covid-19. In the analysis, the relative risk reduction in hospitalization (for >24 hours) or death between patients who received a single 500-mg dose of sotrovimab and those who received placebo was 85%. A total of 3 of 291 patients in the sotrovimab group (1%), as compared with 21 of 292 patients in the placebo group (7%), had disease progression leading to hospitalization (for >24 hours) for any cause or death (relative risk reduction, 85%; 97.24% confidence interval [CI], 44 to 96; P=0.002). All 5 patients who were admitted to the ICU were in the placebo group.
Q: In this interim analysis, what did safety assessments show regarding treatment with sotrovimab?
A: In the safety analysis population, 73 of 430 patients in the sotrovimab group (17%) and 85 of 438 patients in the placebo group (19%) reported an adverse event. The percentage of patients who reported grade 3 or 4 adverse events was lower in the sotrovimab group (2%) than in the placebo group (6%). The percentage of patients with infusion-related reactions was the same in the two groups (1% in each). Serious adverse events occurred in 2% of the patients who received sotrovimab and in 6% of those who received placebo. Most of these events were hospitalizations for Covid-19–related causes. No serious adverse events were considered by the investigators to be related to sotrovimab. Overall, laboratory results were similar in the sotrovimab and placebo groups.
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