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Casirivimab-imdevimab reduces symptomatic COVID-19 in phase 3 trial

A phase 3 clinical trial published in JAMA has found that only 29,0% of 314 asymptomatic COVID-19–infected people living with an infected household member developed symptomatic illness after receiving the monoclonal antibodies casirivimab and imdevimab, compared with 42,3% given a placebo.

A Cidrap report says that scientists from Regeneron, maker of the casirivimab-imdevimab combination Regen-CoV, led the randomised, double-blind trial at 112 sites in the United States, Romania, and Moldova. The combination is available through an emergency use authorisation for high-risk, non-hospitalised COVID-19 patients.

Asymptomatic, SARS-CoV-2 antibody-negative participants 12 years and older who tested positive for COVID-19 within 96 hours of the index case were enrolled from 13 July 2020 to 28 January 2021, with follow-up until 11 March 2021. Participants were randomly assigned to receive one dose of subcutaneous casirivimab-imdevimab (158 participants) or placebo (156). Average participant age was 41.0 years.

The drug combination significantly averted progression to symptomatic illness (29,0% vs 42,3% with placebo), for an odds ratio (OR) of 0,54 and an absolute risk difference of -13,3%.

Casirivimab-imdevimab lowered the risk of symptomatic infection from 19,2% to 10%, the duration of COVID-19 symptoms by 5,6 days per participant, and the symptom duration per 1,000 participants by 489,8 weeks, relative to 811,9 weeks with placebo. The proportion of participants receiving casirivimab-imdevimab who had at least one treatment-emergent adverse event was 33,.5%, versus 48,1% for placebo.

In a secondary analysis, none of 100 casirivimab-imdevimab participants was hospitalised or visited an emergency department because of COVID-19, compared with 6 of 104 in the placebo group.

In a related editorial, Dr Jonathan Li and Dr Rajesh Gandhi, both of Harvard Medical School, said that if casirivimab-imdevimab is authorised for use in asymptomatic COVID-19 patients, the combination could be useful for immunosuppressed patients. “In immunocompetent patients, monoclonal antibodies are likely to be reserved for symptomatic individuals as long as there continue to be supply and logistical constraints,” they wrote.

“However, casirivimab and imdevimab activity is compromised by the Omicron variant, and it is unknown whether the results of this study can be extrapolated to other monoclonal antibody therapies,” they added.

Study details
Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial

Published in JAMA on 14 January 2022

Key Points

Question Does treatment with a subcutaneous combination of casirivimab and imdevimab prevent progression to symptomatic COVID-19 when given to recently infected, asymptomatic individuals?
Findings In this randomised clinical trial that included 314 SARS-CoV-2 reverse transcriptase–quantitative polymerase chain reaction–positive individuals living with an infected household contact, 29.0% of asymptomatic seronegative participants treated with subcutaneous casirivimab and imdevimab, 1200 mg (600 mg of each antibody), developed symptomatic COVID-19 over 28 days vs 42.3% of those treated with placebo. This difference was statistically significant.
Meaning Treatment with subcutaneous casirivimab and imdevimab antibody combination compared with placebo significantly reduced the incidence of symptomatic COVID-19 among recently exposed, asymptomatic individuals.

Abstract

Importance
Easy-to-administer anti–SARS-CoV-2 treatments may be used to prevent progression from asymptomatic infection to symptomatic disease and to reduce viral carriage.
Objective
To evaluate the effect of combination subcutaneous casirivimab and imdevimab on progression from early asymptomatic SARS-CoV-2 infection to symptomatic COVID-19.
Design, Setting, and Participants
Randomised, double-blind, placebo-controlled, phase 3 trial of close household contacts of a SARS-CoV-2–infected index case at 112 sites in the US, Romania, and Moldova enrolled July 13, 2020–January 28, 2021; follow-up ended March 11, 2021. Asymptomatic individuals (aged ≥12 years) were eligible if identified within 96 hours of index case positive test collection. Results from 314 individuals positive on SARS-CoV-2 reverse transcriptase–quantitative polymerase chain reaction (RT-qPCR) testing are reported.

Interventions
Individuals were randomised 1:1 to receive 1 dose of subcutaneous casirivimab and imdevimab, 1200 mg (600 mg of each; n = 158), or placebo (n = 156).

Main Outcomes and Measures
The primary end point was the proportion of seronegative participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. The key secondary efficacy end points were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load (>4 log10 copies/mL).

Results
Among 314 randomised participants (mean age, 41.0 years; 51.6% women), 310 (99.7%) completed the efficacy assessment period; 204 were asymptomatic and seronegative at baseline and included in the primary efficacy analysis. Subcutaneous casirivimab and imdevimab, 1200 mg, significantly prevented progression to symptomatic disease (29/100 [29.0%] vs 44/104 [42.3%] with placebo; odds ratio, 0.54 [95% CI, 0.30-0.97]; P = .04; absolute risk difference, −13.3% [95% CI, −26.3% to −0.3%]). Casirivimab and imdevimab reduced the number of symptomatic weeks per 1000 participants (895.7 weeks vs 1637.4 weeks with placebo; P = .03), an approximately 5.6-day reduction in symptom duration per symptomatic participant. Treatment with casirivimab and imdevimab also reduced the number of high viral load weeks per 1000 participants (489.8 weeks vs 811.9 weeks with placebo; P = .001). The proportion of participants receiving casirivimab and imdevimab who had 1 or more treatment-emergent adverse event was 33.5% vs 48.1% for placebo, including events related (25.8% vs 39.7%) or not related (11.0% vs 16.0%) to COVID-19.

Conclusions and Relevance
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.

 

Cidrap article – Casirivimab-imdevimab reduces symptomatic COVID-19 in phase 3 trial (Open access)

 

JAMA article – Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial (Open access)

 

Realizing the Potential of Anti–SARS-CoV-2 Monoclonal Antibodies for COVID-19 Management (Open access)

 

See more from MedicalBrief archives:

 

FDA expands emergency use of REGEN-COVTM (casirivimab and imdevimab)

 

Casirivimab–Imdevimab reduced hospitalisation of high-risk patients with mild to moderate COVID-19

 

Regeneron antibody cocktail cuts COVID-19 hospitalisation and deaths

 

 

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