A single dose of Evusheld given intramuscularly to unvaccinated, patients with COVID-19 reduced both the need for hospitalisation and death, according to the TACKLE study
A single dose of Evusheld given to non-hospitalised, unvaccinated patients experiencing mild to moderate COVID-19 led to a significant reduction in progression to more severe disease (i.e., hospitalisation) and mortality compared to those given placebo. These were the key findings from the the TACKLE study by a group of UK and US researchers.
Evusheld contains the two monoclonal antibodies, tixagevimab and cilgavimab, which simultaneously bind to distinct, non-overlapping epitopes on the spike protein receptor binding domain and are therefore able to neutralise COVID-19. 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 40kg before potential exposure to the virus.
The combination of monoclonal antibodies has been examined in TACKLE, which is an ongoing, Phase III randomised, double-blind trial conducted in 95 sites across the USA, Latin America, Europe and Japan. Included patients are adults (18 years and over) with a documented, laboratory confirmed PCR or antigen test, COVID-19 infection, at least 3 days before enrolment in the trial. An additional entry requirement is a score of > 1 but less than 4 on the World Health Organization (WHO) Clinical progression Scale.
For the study, all eligible participants were randomised 1:1 to a single dose of Evusheld (600mg, which consists of two consecutive doses of 300mg 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 and higher or all-cause mortality.
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 was associated with a statistical and clinically meaningful reduction in both progression to more severe COVID-19 and death compared with 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