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RCT finds single dose of Evusheld reduces progression of COVID-19 and mortality

A single dose of Evusheld given to unvaccinated, patients with mild to moderate severity COVID-19 reduced both hospitalisation and death

Just a single dose of Evusheld administered to non-hospitalised, unvaccinated patients with mild to moderate COVID-19, resulted in a significant reduction in progression to more severe disease (i.e., hospitalisation) and mortality compared to those given placebo. These were the main findings from the the TACKLE study by a group of UK and US researchers.

Evusheld is a combination of two monoclonal antibodies, tixagevimab and cilgavimab, that simultaneously bind to distinct, non-overlapping epitopes on the spike protein receptor binding domain of COVID-19 and which neutralises the virus. It is administered as a single intra-muscular dose and in march 2022, the EMA granted a marketing authorisation for Evusheld for the prevention of COVID-19 in adults and adolescents from 12 years of age weighing at least 40 kg before potential exposure to the virus.

The effectiveness of the combination has been examined in TACKLE, which is an on-going, phase 3 randomised, double-blind trial undertaken in 95 sites across the USA, Latin America, Europe and Japan. The trial enrolled adults (18 years and over) with a documented, laboratory confirmed PCR or antigen test, positive COVID-19 infection, at least 3 days before entry to the trial. An additional requirement was a score of > 1 but less than 4 on the World Health Organisation (WHO) Clinical progression Scale.

For the study, all eligible participants were randomised 1:1 to a single dose of Evusheld (600 mg, which consists of two consecutive doses of 300 mg of each) or saline solution (which served as the placebo) on the first day of the trial. The primary outcome of the study was a composite endpoint of either severe COVID-19, defined by either the presence of pneumonia, hypoxaemia plus a WHO scale score of 5 or more or death.

Single dose of Evusheld and COVID-19 outcomes

A total of 903 participants with mean age of 46.1 years (50% female) were enrolled and randomised to Evusheld (452) or placebo. Just over half (52%) of participants were of Hispanic or Latino ethnicity with 62% being White and 4% Black or African American. A total of 89% of the entire cohort had at least one or more risk factors for severe COVID-19 including a body mass index > 30 (43%), hypertension (28%), current smokers (40%) and diabetes (12%).

The primary endpoint (severe COVID-19 or death) occurred in 4% of those receiving a single dose of Evusheld and in 9% of those given a placebo and this difference was significant (absolute risk reduction = 4.5%, 95% CI 1.1 – 8.0, p < 0.0001).

In terms of safety, adverse effects occurred in 29% of those given Evusheld and 36% of those using placebo and most were deemed to be of mild or moderate severity.

The authors concluded that a single dose of Evusheld of associated with a statistical and clinically meaningful reduction in both progression to more severe COVID-19 and death compared to placebo among unvaccinated adult patients.

Montgomery H et al. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial Lancet Respir Med 2022

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