AstraZeneca’s Evusheld significantly reduces risk of developing severe COVID-19

We are now in a far improved healthcare position in terms of COVID-19 treatments and vaccine protection. However, the potential threat of complications and disease progression remains a concern for certain individuals, including older adults, those with co-morbidities and various immunocompromised people. Also, the capability of the SARS-CoV-2 virus to mutate means the medical community must remain proactive in finding effective treatments.

Detailed results from an outpatient treatment trial, the TACKLE Phase III, published in The Lancet Respiratory Medicine, showed that Evusheld (tixagevimab and cilgavimab) provided clinically and statistically significant protection against progression to severe COVID-19 or death from any cause compared to placebo. The best results were seen when treatment was administered earlier in the disease course.

TACKLE, the Phase III, randomised, double-blind, placebo-controlled, multi-centre trial, was conducted in non-hospitalised adults with mild-to-moderate COVID-19 who were symptomatic for seven days or less. In the trial, 90 percent of participants were at high risk of progression to severe COVID-19 due to co-morbidities or age.

Hugh Montgomery, Professor of Intensive Care Medicine at University College London, UK, and TACKLE principal investigator, reflected that: “Despite the success of vaccines, many individuals such as older adults, individuals with co-morbidities and those who are immunocompromised, remain at risk for poor outcomes from severe COVID-19. Additional options are needed to prevent disease progression and reduce the burden on healthcare systems, especially with the continued emergence of new variants. The TACKLE results show that one intramuscular dose of Evusheld can prevent these individuals from progressing to severe COVID-19, with earlier treatment leading to even better results.”

Commenting on next steps, Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, explained: “We are discussing the TACKLE data with regulatory authorities and continue to progress submissions in both treatment and prophylaxis indications to help combat COVID-19 on all fronts.”   

Detailed TACKLE results

According to AstraZeneca, the TACKLE trial demonstrated that a single 600mg intramuscular (IM) dose of Evusheld significantly reduced the relative risk of progressing to severe COVID-19 or death (from any cause) by 50 percent through day 29, compared to placebo in non-hospitalised patients with mild-to-moderate COVID-19 who were symptomatic for seven days or less – the trial’s primary endpoint.

Highlighting the increased benefit of earlier treatment, pre-specified analyses of participants who received treatment within three days of symptom onset reduced their risk of developing severe COVID-19 or death (from any cause) by 88 percent compared to placebo, while the risk reduction was 67 percent when participants received Evusheld within five days of symptom onset. 

AstraZeneca also report that Evusheld reduced the risk of respiratory failure, a secondary endpoint, by 72 percent, with three Evusheld participants (0.7 percent) versus 11 placebo participants (three percent) requiring measures such as mechanical ventilation or extracorporeal membrane oxygenation.