Evusheld Significantly Prevents Severe or Fatal COVID-19 Disease Progression

Yesterday, AstraZeneca shared positive phase 3 trial results for Evusheld (tixagevimab and cilgavimab), a dual injectable for early outpatient treatment of mild-to-moderate COVID-19.

“These results…add to the growing evidence supporting the use of Evusheld to help patients who most need additional protection against COVID-19,” said Mene Pangalos, the executive vice president of biopharmaceuticals research and development at AstraZeneca.

Study results from the ongoing TACKLE trial were published yesterday in The Lancet Respiratory Medicine, and showed that Evusheld provided clinically and statistically significant protection against severe COVID-19 disease progression or death by any cause, in comparison to placebo.

Evusheld was originally developed by Vanderbilt University Medical Center researchers. Its long-acting antibody combination, tixagevimab and cilgavimab, are both human monoclonal antibodies derived from B-cells donated by patients who survived a COVID-19 infection.

The phase 3 TACKLE trial is a randomized, double-blind, placebo-controlled study of 903 patients with laboratory confirmed COVID-19 infection. The participants were not vaccinated against COVID-19, had mild-to-moderate infection, were symptomatic for no more than 7 days, and were not hospitalized.

Notably, 90% of the included participants were at high risk of severe or fatal COVID-19 disease progression, due to comorbidities or advanced age.

The study patients were randomized 1:1 to receive 2 sequential intramuscular injections of either Evusheld or a saline placebo. The primary trial endpoint was either severe COVID-19 disease or death from any cause through day 29 of the study.

The trial results showed that a 600 mg dose of Evusheld reduced the risk of severe or fatal COVID-19 by 50%. Evusheld benefits were more significant the earlier patients received their injections. In participants dosed with Evusheld within 3 days of symptom onset, the risk of developing severe or fatal disease reduced by 88% compared to placebo. When treated within 5 days of symptom onset, Evusheld had a risk reduction of 67% compared to placebo.

Hugh Montgomery, the TACKLE principal investigator and a professor of intensive care medicine at University College London, UK, spoke to the importance of developing treatments like Evusheld that reduce the risk of severe or fatal COVID-19 disease. “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.”

Evusheld also reduced the risk of respiratory failure, a secondary endpoint of TACKLE, by 72%. Mechanical ventilation or extracorporeal membrane oxygenation was required by 0.7% (n = 3) of Evusheld recipients, as compared to 3% (n = 11) of placebo recipients.

Evusheld was generally well-tolerated, with adverse events more frequently reported among the placebo recipients. The most common adverse event of both cohorts was COVID-19 pneumonia, occurring in 11% (n = 49) of the placebo group and 6% (n = 26) of the Evusheld group.

Evusheld was approved by Health Canada for COVID-19 pre-exposure prophylaxis in April 2022, and received Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA) in December 2021. In late February, the FDA recommended approved populations receive a higher dosage of Evusheld to ensure protection against the highly infectious Omicron variant.

“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,” Pangalos said.