Antibody cocktail is efficacious in COVID-19 outpatients

Evaluation of an antibody cocktail of casirivimab plus imdevimab for patients with mild-to-moderate COVID-19 showed a risk reduction of all-cause death of over 70% and markedly reduced persistence of symptoms in the adaptive phase 1–3 REGN-COV 2067 study.

“The casirivimab and imdevimab combination comprises 2 potent neutralising monoclonal antibodies that bind non-competing epitopes on the SARS-CoV-2 2 spike protein,“ Dr Julie V. Philley (University of Texas Health Science Center, Tyler, USA) explained in her talk in which she presented results from the clinical trial REGN-COV 2067 (NCT04425629) [1]. This adaptive phase 1/2/3 study tested dual therapy with casirivimab and imdevimab in outpatients with mild-to-moderate COVID-19. Among the prerequisites for study subjects were central lab-confirmed disease <72 hours and appearance of symptoms ≤7 days prior to randomisation. Initially, randomisation was performed 1:1:1 to 8,000 mg, 2,400 mg, and placebo but after the analysis of the phase 1/2 data, the protocol was changed with a re-randomisation to 2,400 mg, 1,200 mg, or placebo, eligible only for patients with ≥1 risk factor for severe disease. After a single infusion with the dual therapy or placebo on day 1, patients were followed until day 29. The primary endpoint was defined as the proportion of patients with ≥1 hospitalisation or all-cause death, whereas the timespan until COVID-19 symptoms resolved was among the secondary endpoints.

“Patients were well matched across the treatment and placebo groups: median age was 48.5 years, 58% were obese, 49% were male, and approximately 1/3 were Hispanic or Latino. Medium viral load was approximately 7 log₁₀ copies and 69% had a negative baseline SARS-CoV-2 serum antibody status,” Dr Philley described the study cohort. She also remarked that the presence of risk factors was well balanced between the study arms.

In the group receiving 2,400 mg of casirivimab plus imdevimab, the relative risk of all-cause death decreased by 71% (P<0.0001). In the subgroup analysis, COVID-19-related hospitalisations and all-cause death were also significantly reduced. This included patients with high viral loads and high or low baseline seropositivity. The duration of symptoms also decreased by 4 days under the dual therapy at both dosages and, again, the result was consistent across the subgroups.

In terms of safety, casirivimab plus imdevimab was well tolerated with more fatal outcomes in the pooled placebo groups (0.3%) than in the treatment arms (0.1% with 1,200 mg; <0.1% with 2,400 mg, and 0 with 8,000 mg).

1. Philley JV, et al. Casirivimab with Imdevimab, a cocktail of two antibodies against SARS-CoV-2, in the outpatient setting: phase 3 efficacy and safety results. Session B007-Breaking news: clinical trial results in pulmonary medicine. ATS 2021 International Conference, 14-19 May.

Posted on 20 May 20214 August 2021