Antibody treatment for COVID-19: a combination is successful

Dual therapy with casirivimab plus imdevimab was investigated as treatment for patients with mild-to-moderate COVID-19. The results not only showed a risk reduction for death of over 70%, but also a 4-day reduction of disease duration. This was found in the adaptive phase 1/2/3 REGN-COV 2067 trial.

As a high viral load of SARS-CoV-2 was linked to worse outcomes of COVID-19, monoclonal antibodies with the ability to counteract the virus have come into focus for possible treatment [1]. Research results for antibody treatment of other viral infections such as Ebola led Dr Julie V. Philley (University of Texas Health Science Center, USA) and colleagues to hypothesise that a treatment approach with combined antibodies could be beneficial [2]. “The casirivimab and imdevimab combination comprises 2 potent neutralising monoclonal antibodies that bind non-competing epitopes on the SARS-CoV-2 spike protein,“ Dr Philley described in her talk presenting results from the REGN-COV 2067 clinical trial (NCT04425629) [3].

The 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 phase 1/2, 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 casirivimab/imdevimab 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 the placebo groups: median age was 48.5 years, 58% were obese, 49% were men, and approximately one-third 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/imdevimab, the relative risk of all-cause death decreased by 71% (P<0.0001) (see Figure). Concerning subgroups, 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 casirivimab/imdevimab at both dosages and, again, the result was consistent across the subgroups.

Figure: Comparison of casirivimab/imdevimab versus placebo for all-cause death and COVID-19-induced hospitalisations [3]



 

CI, confidence interval; HR, hazard ratio; IV, intravenous; mFAS, modified full analysis set.

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

1. Fajnzylber J, et al. Nat Commun. 2020;11(1):5493.
2. Mulangu S, et al. N Engl J Med. 2019;381(24):2293-2303.
3. 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.

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Posted on 5 July 20215 July 2021