The combination of casirivimab and imdevimab is approved for emergency use to prevent Covid-19 in high-risk adults and children (older than 12 years of age and weighing at least 40 kg) who likely to develop severe COVID-19, including hospitalization or death.

Now a New England Journal of Medicine study has shown that the two monoclonal antibodies, casirivimab and imdevimab administered together, also prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons.1

Researchers conducted a two-part multicenter study to examine the effectiveness of casirivimab _ imdevimab in preventing SARS-CoV-2 infection among previously uninfected household contacts of infected persons (Part A) and in treating recently infected asymptomatic persons (Part B). The participants were screened at baseline and the effectiveness of treatment was assessed at 28 days.

All the previously uninfected household contacts of an index patient were recruited for the study within 96 hours after collection of the index patient’s positive SARS-CoV-2 diagnostic test sample.

All participants were older than 12 years of age. All those persons who had been earlier been infected were not included in the trial. The study participants were then randomly assigned to treatment with 1200 mg of casirivimab and imdevimab combination  (600 mg each)  administered subcutaneously or placebo. The study group included 753 participants, while the placebo group included 752 participants. The primary efficacy end point was the development of RT PCR-confirmed symptomatic infection up to 28 days.

Treatment with the combination of the two monoclonal antibodies was found to overall prevent all infections, both symptomatic and asymptomatic, with a relative risk reduction of 66.4%. Only eleven of the 753 patients in the study group who developed Covid-19 became symptomatic, whereas this number was higher (59) in the placebo group; 1.5% vs 7.8%, respectively with a relative risk reduction of 81.4%.

After the first week of starting treatment, two out of the 753 patients in the study group developed symptoms compared to 27 in the placebo group; 0.3% vs 3.6%, respectively with a relative risk reduction of 92.6%. In symptomatic patients, symptoms resolved faster in those treated with the monoclonal antibodies (1.2 weeks) compared to the placebo treated patients (3.2 weeks).

Similarly, the high viral load (>104 copies per mL) persisted for a longer duration in the placebo treated group than in the patients treated with the combination of monoclonal antibodies; 0.4 weeks and 1.3 weeks, respectively with a relative risk reduction of around 86%. Moreover, in participants in whom either symptomatic or asymptomatic infection developed, the magnitude and duration of detectable RNA (i.e., the peak viral load and weeks of RT-qPCR positivity) were markedly lower in the REGEN-COV group than in the placebo group.

The monoclonal antibodies combination was well-tolerated with only minor adverse events in some patients.

The study authors therefore concluded that the casirivimab and imdevimab combination was effective in not only preventing SARS-CoV-2 infection in the uninfected and previously uninfected household contacts of a patient with Covid-19, it also reduced the duration of symptoms and high viral load.

Reference

1. OBrien MP, et al; Covid-19 Phase 3 Prevention Trial Team. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med. 2021 Sep 23;385(13):1184-1195. doi: 10.1056/NEJMoa2109682. Epub 2021 Aug 4.