Antibody Treatment Provides Clinically Significant Protection Against Severe COVID-19

The peer-review journal The Lancet Respiratory Medicine published results from a phase 3 study on July 8, 2022, that found 'Early intramuscular administration of the Evusheld (tixagevimab–cilgavimab) SARS-CoV-2-neutralising monoclonal antibody (mAbs) combination to non-hospitalized adults has potential to prevent disease progression.'

The estimated cumulative incidence of sustained recovery was 89% for tixagevimab–cilgavimab and 86% for placebo group participants at day 90 in the full cohort (recovery rate ratio [RRR] 1·08 [95% CI 0·97–1·20]; p=0·21).

Results were similar in the seronegative subgroup (RRR 1·14 [0·97–1·34]; p=0·13).

Mortality was lower in the tixagevimab–cilgavimab group (61 [9%]) versus the placebo group (86 [12%]; hazard ratio [HR] 0·70 [95% CI 0·50–0·97]; p=0·032).

The composite safety outcome occurred in 178 (25%) tixagevimab–cilgavimab and 212 (30%) placebo group participants (HR 0·83 [0·68–1·01]; p=0·059).

And serious adverse events occurred in 34 (5%) participants in the tixagevimab–cilgavimab group and 38 (5%) in the placebo group.

This study's Interpretation was: Among patients hospitalized with COVID-19 receiving remdesivir and other standard care, tixagevimab–cilgavimab did not improve the primary outcome of time to sustained recovery but was safe, and mortality was lower.

Data were analyzed as part of an international NIH-sponsored clinical trial, including a site at Duke Health that enrolled about 10% of the study participants.

Previously, U.K.-based AstraZeneca announced on June 8, 2022, that detailed results from the TACKLE Phase III outpatient treatment trial showed AstraZeneca's Evusheld provided clinically and statistically significant protection against progression to severe COVID-19 or death from any cause compared to placebo, with treatment with Evusheld earlier in the disease course leading to more favorable outcomes.

This AstraZeneca-funded clinical trial concluded on June 7, 2022, that 'A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favorable.'

And 'treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favorable outcomes.

Hugh Montgomery, Professor of Intensive Care Medicine at University College London and the TACKLE study principal investigator, commented in a press release issued on June 8, 2022, "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."

• In TACKLE, 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% (95% confidence interval [CI] 15, 71; p=0.010) through day 29 compared to placebo in non-hospitalized patients with mild-to-moderate COVID-19 who were symptomatic for seven days or less, the trial's primary endpoint.
• In pre-specified analyses of participants who received treatment within three days of symptom onset, Evusheld reduced the risk of developing severe COVID-19 or death (from any cause) by 88% compared to placebo (95% CI 9, 98), and the risk reduction was 67% (95% CI 31, 84) when participants received Evusheld within five days of symptom onset.  
• Evusheld also reduced the risk of respiratory failure, a secondary endpoint, by 72% (95% CI 0.3, 92; nominal p=0·036), with three Evusheld participants (0.7%) versus 11 placebo participants (3%) requiring measures such as mechanical ventilation or extracorporeal membrane oxygenation.

"Additional options are needed to prevent disease progression and reduce the burden on healthcare systems, especially with the continued emergence of new variants," concluded Montgomery.

On June 29, 2022, the U.S. FDA revised the Evusheld Fact Sheet for Healthcare Providers to recommend repeat dosing every six months with a dose of 300 mg of tixagevimab and 300 mg cilgavimab if patients need ongoing protection. 

The previous Fact Sheet for Healthcare Providers did not provide a specific recommendation on the dosing interval.

For further details, please refer to the FDA’s FAQs for Evusheld.

In the USA, Evusheld has been distributed by the U.S. government since December 2021. As of July 3, 2022, about 771,553 Evusheld doses have been distributed in the USA.

In February 2022, the U.S. Defense Department awarded AstraZeneca an $855 million contract to manufacture, distribute, and store Evusheld for the general population. 

Additional mAbs news is posted at CoronavirusToday.

Note: This information was manually curated for mobile readership.

Update: This article was amended for various clarifications, dates and citations on July 11, 2022.