REGEN-COV Prevents COVID-19 Infection in Previously Uninfected Household Contacts of Infected Subjects

30 Dec, 21

Introduction

REGEN-COV, a combination of two neutralizing monoclonal antibodies casirivimab and imdevimab, binds the noncompeting epitopes of receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Studies have demonstrated that REGEN-COV reduces the risk of hospitalization or death, reduces the viral load and shortens the duration of symptoms among patients with coronavirus disease 2019 (Covid-19).

Aim

The study evaluated the efficacy and safety of subcutaneous REGEN-COV in previously uninfected household contacts of infected persons (Part A) and in treating recently infected asymptomatic persons (Part B).

Method

Study Design

Randomized, double-blind, placebo-controlled 2-part study.

Patient Profile

Asymptomatic healthy adolescents aged 12-17 years and adults aged >18 years who were household contacts of an index person (first person with SARS-CoV-2 infection) and living with the index person for 28 days

Treatment Strategy

At screening, the nasopharyngeal swabs and serum samples were tested and were enrolled within 96 hours after a household contact was diagnosed with SARS-CoV-2 infection.
Part A involved subjects with negative reverse-transcriptase–quantitative polymerase-chain-reaction (RT-qPCR) test and part B involved subjects with positive RT-qPCR test.
The participants were randomized in a 1:1 ratio to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection.
The participants were stratified according to age and the results of the local diagnostic assay for SARS-CoV-2.
The trial consisted of 1-day screening period, 28-day efficacy assessment period and a 7-month follow-up period.
Nasopharyngeal swabs were tested at baseline and throughout the efficacy assessment period.

Endpoints

% of participants who developed SARS-CoV-2 infection through day 28 confirmed by RT-qPCR
Duration of high viral load
Duration of symptoms
Adverse events (AEs)

Results

The primary efficacy analysis cohort comprised 753 and 752 subjects who received REGEN-COV and placebo respectively.
Symptomatic SARS-CoV-2 infection developed in 1.5% and 7.8% in the REGEN-COV group and placebo group respectively; (relative risk reduction 81.4%; p<0.001).
In weeks 2 to 4, 0.3% and 3.6% developed symptomatic SARS-CoV-2 infection in the REGEN-COV and placebo groups respectively; relative risk reduction, 92.6%.
Overall, asymptomatic or symptomatic infection occurred in 4.8% and 14.2% in REGEN-COV and placebo respectively (relative risk reduction, 66.4%).
The median time to resolution of symptoms among symptomatic infected participants was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively).
The REGEN-COV reduced the duration of a high viral load (>10⁴ copies per ml); 0.4 weeks vs 1.3 weeks.
The participants who became infected despite receiving REGEN-COV had a lower peak viral load and shorter duration of high viral load as compared to those infected in placebo group.
The incidence of atleast 1 AE was 20.2% vs 29% in the REGEN-COV and placebo groups respectively.
Atleast 1 serious AE was reported in 0.8% and 1.1% in both groups. However, they were not drug related.
There were no dose-limiting toxic effects of REGEN-COV noted.

Conclusion

A single subcutaneous REGEN-COV injection prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons.
Administration of REGEN-COV resulted in shorter duration of symptoms and reduced the duration of high viral load, among the participants who became infected.

N Engl J Med 2021; 385:1184-1195. Doi: 10.1056/NEJMoa2109682.