Monoclonal antibody cocktail cut COVID-19 hospitalization, death by 70% in outpatient setting
A cocktail of two monoclonal antibodies — casirivimab and imdevimab — significantly reduced the risk for hospitalization or death in nonhospitalized patients with COVID-19, according to results of a phase 3 pivotal trial.
Casirivimab with imdevimab (REGEN-COV, Regenerson) also shortened symptom duration and reduced viral load, researchers reported during a breaking news session at the American Thoracic Society International Conference.
“In this phase 3 study [of] patients with confirmed COVID-19, a single IV dose of casirivimab with imdevimab compared with placebo significantly reduced hospitalizations or death by 70%, significantly shortened duration of symptoms by 4 days and the results were consistent across subgroups, including those with high baseline viral load who have been shown to have a poor prognosis with higher incidence of hospitalizations and longer symptom duration,” Julie Philley, MD, pulmonary critical care physician and chair of internal medicine at the University of Texas Health Sciences Center, Houston, said during the presentation.
The phase 3, randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of REGEN-COV in 4,567 adults (mean age, 48.5 years; 49% men) with confirmed COVID-19 infection but who were not hospitalized. All patients had at least one risk factor for severe COVID-19, including chronic lung disease, asthma, obesity, cardiovascular disease and older age.
The trial evaluated two REGEN-COV doses: 2,400 mg and 1,200 mg. the 2,400 mg dose is currently authorized for emergency use by the FDA and the lower dose is under evaluation, according to a company press release. Patients were randomly assigned to receive casirivimab plus imdevimab at 2,400 mg or 1,200 mg or placebo within 7 days of symptom onset and within 72 hours of a positive SARS-CoV-2 test. Follow-up was 28 days. During follow-up, patients underwent nasal swabs and daily electronic clinical outcomes assessment and were monitored for safety with medically attended visits.
The trial met its primary endpoint — the percentage of patients with at least one COVID-19-related hospitalization or all-cause death at day 29 — and all secondary endpoints, with similar efficacy observed for both doses of REGEN-COV.
Patients assigned REGEN-COV 2,400 mg had a 71% reduction in the risk for COVID-19-related hospitalization or all-cause death at day 29 compared with placebo (P < .0001) and those assigned the 1,200 mg dose had a 70% reduction in the primary endpoint compared with placebo (P < .0024). Differences in the primary outcome between the groups were evident by day 4 and continued through day 29, she said.
Both doses of REGEN-COV were associated with a shorter mean time to COVID-19 symptom resolution compared with placebo (10 days vs. 14 days).
REGEN-COV at both doses reduced viral load by 0.71 log10 copies/mL and 0.86 log10 copies/mL at 7 days compared with placebo (P < .0001 for both).
Results were consistent across various subgroups, according to Philley.
Researchers conducted a safety assessment in 5,531 patients up to day 169. Both doses of REGEN-COV were well tolerated with no identified safety concerns. Serious adverse events were largely related to COVID-19 and occurred in 1.1% of patients assigned REGEN-COV 1,200 mg, 1.3% of those assigned 2,400 mg and 4% of those assigned placebo. There were five deaths in the placebo group, one in the 1,200 mg group and 1 in the 2,400 mg group, according to the release.
REGEN-COV is an investigational monoclonal antibody cocktail that is authorized for emergency use in the United States in patients with mild to moderate COVID-19 at high risk for severe disease or hospitalization. The cocktail is administered intravenously. REGEN-COV is also being assessed in other settings. In April, Regeneron announced positive results of a phase 3 trial that showed REGEN-COV prevented COVID-19 infection in household contacts of individuals infected with SARS-CoV-2. Read Healio’s coverage of that trial here.
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Editor's Note: This article was updated on May 18, 2021, to clarify that patients in the trial had confirmed COVID-19 infection and at least one risk factor for severe COVID-19.