Casirivimab-imdevimab combo prevents progression from asymptomatic to symptomatic COVID-19

Treatment with the combination therapy of casirivimab and imdevimab prevents the risk of developing symptomatic COVID-19 among asymptomatic individuals with SARS-CoV-2 infection in a household close-contact setting, according to a recent study.

“Although the primary analysis population focused on participants without evidence of prior infection (seronegative), … casirivimab and imdevimab reduced the risk of developing symptomatic infection vs placebo by 35.4 percent and 33.9 percent, respectively,” said the researchers.

The phase III trial analysed 314 individuals (mean age 41.0 years, 51.6 percent female) with SARS-CoV-2 infection but were asymptomatic at baseline, who subsequently developed signs and symptoms of COVID-19 within 14 days of the RT-qPCR* result. A weekly RT-qPCR testing was performed to determine SARS-CoV-2 viral load during the 28-day efficacy assessment period or until tested negative on two consecutive nasopharyngeal swabs. Participants were randomized to receive either subcutaneous casirivimab and imdevimab 1,200 mg, at a dose of 600 mg each (n=155), or placebo (n=156). [JAMA 2022;doi:10.1001/jama.2021.24939]

Of the 204 asymptomatic and seronegative infected participants at baseline, significantly fewer individuals developed symptomatic COVID-19 in the casirivimab-imdevimab group than the placebo group within 28 days (29.0 percent vs 42.3 percent; odds ratio, 0.54; p=0.04).

The casirivimab-imdevimab group also demonstrated a significantly shorter duration of symptomatic SARS-CoV-2 infection than the placebo group (895.7 vs 1,637.4 weeks per 1,000 individuals; p=0.03), with a mean duration of 3.1 vs 3.9 weeks per symptomatic participant, respectively.

Casirivimab-imdevimab recipients also experienced a significantly reduced total number of weeks with high viral load (>4 log₁₀ copies/mL) than the placebo recipients (489.8 vs 811.9 weeks per 1,000 individuals; p=0.001), with a mean reduction of 0.5 vs 0.8 weeks per participant with high viral load, respectively.

Of note, as early as day 8, a noticeable reduction in nasopharyngeal SARS-CoV-2 viral load was observed among those on casirivimab-imdevimab vs those on placebo (adjusted least-squares mean difference, -1.5 log₁₀ copies/mL).

In a post hoc analysis, when assessing individuals who only had infections at day 4, those on casirivimab-imdevimab showed a reduced risk of developing symptomatic infection than those on placebo (5.0 percent vs 21.2 percent), “but this finding should be considered hypothesis generating,” noted the researchers.

Lower rates of grade ≥1 treatment-emergent adverse events (TEAEs) were observed in the casirivimab-imdevimab group than the placebo group (33.5 percent vs 48.1 percent), with fewer AEs related to COVID-19 (25.8 percent vs 39.7 percent).

No serious TEAEs were observed in the casirivimab-imdevimab group, while four events were noted in the placebo group, but no deaths were reported in either treatment group.

“Among asymptomatic SARS-CoV-2 RT-qPCR-positive individuals living with an infected household contact, treatment with subcutaneous casirivimab and imdevimab antibody combination vs placebo significantly reduced the incidence of symptomatic COVID-19 over 28 days,” the researchers concluded.

“In all participants combined, casirivimab and imdevimab reduced the duration of symptoms in those who became symptomatic, reduced the duration of weeks of detectable viral load and high viral load, and reduced peak viral load, with similar numerical trends in the seropositive-only population in most analyses,” noted the researchers.

“Reductions in progression to symptomatic infection and in other outcomes as observed herein would be of potential clinical relevance for use of monoclonal antibody therapies in early treatment of COVID-19,” they added.

*RT-qPCR: Reverse transcriptase-quantitative polymerase chain reaction