Effectiveness of Casirivimab-Imdevimab Monoclonal Antibody Treatment Among High-Risk Patients With Severe Acute Respiratory Syndrome Coronavirus 2 B.1.617.2 (Delta Variant) Infection

Abstract

BACKGROUND Real-world data on the effectiveness of neutralizing Casirivimab-Imdevimab monoclonal antibody (Cas-Imd mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among high-risk patients may inform the response to future SARS-CoV-2 variants. METHODS This study covers an observational retrospective data analysis in Banner Health Care System sites, mainly in Arizona. During the study period, the prevalence of SARS-CoV-2 Delta variant was between 95% and 100%. Out of 29,635 patients who tested positive for COVID-19 between 8/1/2021 and 10/30/2021, in Banner Health Care System, the study cohort was split into 4213 adult patients who received Cas-Imd mAb (1200 mg) treatment compared to a propensity-matched 4213 untreated patients. The primary outcomes were the incidence of all-cause hospitalization, intensive care unit (ICU) admission, and mortality within 30 days of Cas-Imd mAb administration or COVID-19 Delta variant infection. RESULTS Compared to the propensity matched untreated cohort, the Cas-Imd mAb cohort had significantly lower all-cause hospitalization (4.2% vs 17.6%; difference in percentages and 95% confidence interval [CI] -13.4 [-14,7, -12.0], P <.001), ICU admission (0.3% vs 2.8%; difference and CI -2.4 [-3.0, -1.9], P <.001), and mortality (0.2% vs 2.0%; difference and CI -1.8 [-2.3, -1.3], P <.001) within 30 days. The Cas-Imd mAb treatment was associated with lower rate of hospitalization (hazard ratio [HR], 0.22; 95% CI, 0.19-0.26; P <.001) and mortality (HR, 0.11; 95% CI, 0.06-0.21; P<.001). CONCLUSIONS Cas-Imd mAb treatment was associated with a lower hospitalization rate, ICU admission, and mortality within 30 days among patients infected with COVID-19 Delta variant.

Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy

“…REGEN-COV is a combination of two fully human non-competing mAbs, casirivimab (REGN10933) and imdevimab (REGN10987), both of which target the ACE2-binding interface of SARS-CoV-2 RBD and function to block RBD/ACE2 interaction 16 . In vitro experiments demonstrated that the combination could neutralise mutants selected 17 ( https://www.covid19treatmentguidelines.nih.gov/therapies/anti-sars-cov-2-antibody-products/anti-sars-cov-2-monoclonal-antibodies/ ) using single components 18 , 19 . A previous report also suggested that treatment with REGEN-COV would be unlikely to lead to the emergence of escape mutants in both preclinical and human studies 20 .…”

Genome-first detection of emerging resistance to novel therapeutic agents for SARS-CoV-2

“…REGEN-COV is a cocktail of two fully human non-competing nmAbs, casirivimab (REGN10933) and imdevimab (REGN10987), both of which target the ACE2-binding interface of SARS-CoV-2 RBD and function to block RBD/ACE2 interaction (Hansen et al, 2020). In vitro experiments demonstrated that the cocktail could neutralise mutants selected (Al-Obaidi et al, 2022) (https://www.covid19treatmentguidelines.nih.gov/therapies/anti-sars-cov-2-antibody-products/anti-sars-cov-2-monoclonal-antibodies/) using single components (Baum et al, 2020; Liu et al, 2021). A previous report also suggested that treatment with REGEN-COV would not lead to the emergence of escape mutants in both preclinical and human studies (Copin et al, 2021).…”

Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID‐19: A rapid review and meta‐analysis

“…However, it effectively declined ED visits in COVID-19 patients. Studies23,[40][41][42][43][44][45] demonstrate that patients treated with antiviral agents were significantly less likely to be admitted to ICU and visit the ED compared with untreated patients.…”