Combination monoclonal antibody treatment with casirivimab and imdevimab was found to be safe and effective for preventing hospitalization or death from any cause in outpatients at increased risk for severe SARS-CoV-2 infection, according to results of a phase 3 study published in the New England Journal of Medicine.

In this phase 3 portion of a multicenter, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov identifier: NCT04425629), researchers assessed the effects of casirivimab/imdevimab for the treatment of SARS-CoV-2 infection in outpatients at increased risk for severe disease. Patients were randomly assigned in a 1:1:1 fashion to receive either intravenous casirivimab/imdevimab at a dose of either 1200 mg (n=736) or 2400 mg (n=1355) or placebo (n=1341). Eligible patients included those who were aged 18 years and older, tested positive for SARS-CoV-2 infection at baseline, and had at least 1 risk factor for severe disease. The primary outcome was the percentage of patients who were either hospitalized due to severe disease or died from any cause during the 29-day follow-up period. A key secondary outcome was the median time to resolution of COVID-19 symptoms from day 4 to day 29.

Among patients included in the study, the median age was 50 (interquartile range, 38-59) years, 49% were men, and 35% were Hispanic. The most common risk factors were obesity (52%) and cardiovascular disease (36%). In addition, 3% of patients were immunocompromised.


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The researchers noted that COVID-19 related hospitalization or death occurred more often among patients treated with the 2400-mg dose of casirivimab/imdevimab vs those treated with placebo (4.6% vs 1.3%).  Of note, the researchers found that treatment with casirivimab/imdevimab 2400 mg was associated with a relative risk reduction of 71.3% (95% CI, 51.7-82.9; P <.001).

Compared with patients treated with a 1200-mg dose of casirivimab/imdevimab, COVID-19-related hospitalization or death occurred more often among those treated with placebo (3.2% vs 1.0%, respectively). In addition, the researchers noted that treatment with casirivimab/imdevimab 1200 mg was associated with a relative risk reduction of 70.4% (95% CI, 31.6-87.1; P =.002).

The researchers observed that the median time to resolution of COVID-19 symptoms was decreased among patients treated with either dose of casirivimab/imdevimab compared with those treated with placebo (10 vs 14 days, respectively; P <.001 for both comparisons).

Findings were similar across various subgroups, including in patients who were positive for COVID-19 serum antibodies at baseline.

Among the 5 patients who died during the 29-day follow-up period, 1 was treated with the 1200-mg dose of casirivimab/imdevimab, 1 was treated with the 2400-mg dose, and 3 received placebo.

Serious adverse events occurred more frequently among patients in the placebo group (4.0%) vs those in either the casirivimab/imdevimab 1200 mg group (1.1%) or the 2400-mg dose group (1.3%). Of note, infusion-related reactions that were grade 2 or higher occurred in less than 0.3% of all patients included in the study.

Additional analyses found that treatment with casirivimab/imdevimab decreased both the length of hospitalization incident intensive care unit admissions in patients who were hospitalized. In patients without risk factors for severe disease, the median time to resolution of symptoms was decreased by 2 to 3 days among those treated with either dose of casirivimab/imdevimab vs those treated with placebo.

This study was limited in its ability to assess the effects of casirivimab/imdevimab on mortality due to the small number of deaths that occurred among the included patients.

Casirivimab/imdevimab at a dose of 1200 mg received emergency use authorization in June 2021, replacing the 2400-mg dose.

These findings “showed that [casirivimab/imdevimab] is associated with a clinical benefit, regardless of baseline serum antibody status, so that serologic testing at the time of COVID-19 diagnosis is less critical for making clinical treatment decisions,” the researchers concluded.

Disclosure: This study was supported by Regeneron Pharmaceuticals, and some author(s) declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of funding sources and disclosures.

Reference

Weinreich DM, Sivapalasingam S, Norton T, et al. REGEN-COV antibody combination and outcomes in outpatients with Covid-19. N Engl J Med. Published online September 29, 2021. doi:10.1056/NEJMoa2108163