AZD7442 cocktail protects against symptomatic COVID-19 illness

Intramuscular administration of single-dose AZD7442, a combination of two long-acting monoclonal antibodies (tixagevimab and cilgavimab), significantly reduced the risk of developing symptomatic COVID-19 in adults, according to the PROVENT* study presented at IDWeek 2021.

“Although vaccines effectively prevent COVID-19, some individuals remain at risk of developing COVID-19, … [that is why] we are now shifting to a different approach, which is pre-exposure prophylaxis, [and] we know that prevention is always better than treatment,” said lead author Professor Myron Levin from the University of Colorado School of Medicine in Aurora, Colorado, US.

“Therefore, additional options for preventing COVID-19 are needed, … [and] AZD7442 is a cocktail of monoclonal antibodies that are designed for pre-exposure prophylaxis of COVID-19 in adults,” he added.

This phase III, double-blind, placebo-controlled, multicentre study enrolled 5,197 unvaccinated adults (mean age 53 years) who were at increased risk for inadequate response to vaccination and/or SARS-CoV-2 infection. All participants had a negative point-of-care SARS-CoV-2 serology test at baseline. Participants were randomized in a 2:1 ratio to receive either a single intramuscular dose of AZD7442 300 mg (150 mg each of tixagevimab and cilgavimab; n=3,460) or placebo (n=1,737). [IDWeek 2021, abstract LB5]

At a median follow-up of 83 days, the risk of developing symptomatic COVID-19 was significantly reduced by 77.0 percent in the AZD7442 group vs the placebo group (hazard ratio, 0.23, 95 percent confidence interval, 0.10–0.53; p<0.001). This result “shows that the primary endpoint was met,” Levin highlighted.

Overall, adverse events (AEs) were balanced between the two treatment groups, with 35.3 percent and 34.2 percent of patients reporting ≥1 AE in the AZD7442 and the placebo groups, respectively. Most AEs were considered mild or moderate in severity.

There were no COVID-19 cases reported in the AZD7442 group, while two COVID-19-related deaths were reported in the placebo group.

“Overall, the intramuscular single dose of AZD7442 demonstrated statistically significant protection against SARS-CoV-2 RT-PCR-positive symptomatic illness … [and was well tolerated with] a favourable safety profile,” Levin concluded.

“AZD7442 is the first long-acting combination of monoclonal antibodies that represents a potential new option to augment COVID-19 prevention … [and] preliminary pharmacokinetic modelling predicts potential protection for up to 12 months, [but] with ongoing clinical studies to [further] evaluate this,” he added.

*PROVENT: Phase III double-blind, placebo-controlled study of AZD7442 for pre-exposure prophylaxis of covid-19 in adult