AstraZeneca’s Evusheld Reduces Risk of Severe COVID-19 or Death by at Least 50% in Positive TACKLE Phase III Trial

Compiled by Fan Dongdong

Recently, AstraZeneca announced that the positive results of the TACKLE Phase III trial for Evusheld (tixagevimab and cilgavimab, formerly known as AZD7442), used for the early outpatient treatment of mild to moderate COVID-19, have been published in The Lancet Respiratory Medicine.

The trial results show that, compared with placebo, a single dose of Evusheld reduced the risk of non-hospitalized patients with mild to moderate COVID-19 progressing to severe COVID-19 or death by 50%. In patients treated within 3 days of symptom onset, the drug reduced the risk by 88%.

Evusheld was initially discovered by researchers at Vanderbilt University Medical Center. The therapy is a combination of two long-acting antibodies, tixagevimab and cilgavimab, both of which are human monoclonal antibodies derived from B cells donated by patients after SARS-CoV-2 infection. Vanderbilt licensed Evusheld to AstraZeneca for further development in June 2020.

This randomized, double-blind, placebo-controlled Phase III trial involved participants who were unvaccinated against COVID-19, had a laboratory-confirmed record of SARS-CoV-2 infection, were experiencing mild to moderate COVID-19, had symptom onset within 7 days or less, and were not hospitalized.

903 participants were randomly assigned in a 1:1 ratio to receive either Evusheld or a saline placebo, administered through two separate consecutive intramuscular (IM) injections. The trial's endpoint was whether the participants developed severe COVID-19 or died from any cause by Day 29.

The results showed that, compared with placebo, a single 600mg dose of Evusheld in non-hospitalized patients with mild to moderate COVID-19 significantly reduced the relative risk of progressing to severe COVID-19 or death by 50% on day 29.

Moreover, the earlier the patients receive the injection, the more benefits Evusheld will provide. Compared with the placebo, in patients who received the injection within three days after the onset of symptoms, Evusheld reduced the risk of developing severe COVID-19 or death by 88%. When participants were treated with Evusheld within five days after symptom onset, the associated risk was reduced by 67% compared to the placebo.

As a secondary endpoint of the trial, the study also measured the rate of respiratory failure. Evusheld is expected to help reduce the risk of respiratory failure by 72%. In addition, Evusheld showed good tolerability in the trial, while the incidence of adverse events was higher in the placebo group than in the treatment group, at 36% and 29%, respectively.

Hugh Montgomery, professor of intensive care medicine at University College London and principal investigator of the Tackle trial, stated that despite significant progress in vaccination, many people (such as the elderly, those with comorbidities, and immunocompromised individuals) still face the risk of adverse outcomes from COVID-19 infection. Therefore, additional treatment options are still needed to prevent disease progression and alleviate the burden on healthcare systems, especially as new variants of COVID-19 continue to emerge.

Montgomery emphasized that the Tackle trial results show a single intramuscular injection of Evusheld can prevent these individuals from ultimately developing severe COVID-19, and early treatment also leads to better prognostic outcomes.

Evusheld was approved by Health Canada in April last year for pre-exposure prophylaxis of COVID-19 in immunocompromised populations. This therapy had also received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration in December 2021 for pre-exposure prophylaxis of COVID-19.

AstraZeneca’s Executive Vice President of BioPharmaceuticals R&D, Mene Pangalos, said that the positive results of the trial add to the growing body of evidence supporting the use of Evusheld to help patients who need extra protection against COVID-19 the most. Pangalos mentioned that discussions with regulatory authorities regarding the TACKLE trial data are currently underway, and submissions for both treatment and prevention indications continue to progress in order to combat the COVID-19 pandemic on all fronts.

Reference Source:

AstraZeneca’s Evusheld Successfully Prevents Progression to Severe COVID-19