In the primary efficacy analysis, the risk of developing symptomatic COVID 19 was reduced by 77% with AZD7442.
Although vaccination is a key COVID-19 prevention measure, additional prophylaxis options are necessary for individuals who are either ineligible for immunization or who have comorbidities that could contribute to a reduced immune response to a vaccine.
In phase 3 trial results presented in a late-breaking session at IDWeek 2021, AZD7442 demonstrated statistical significance in protecting against symptomatic COVID-19 infection and was well-tolerated among the study population.
The agent, in development by AstraZeneca, comprises a combination of 2 long-acting antibodies—tixagevimab (AZD8895) and cilgavimab (AZD1061)—which were derived from B-cells donated by convalescent patients who had been infected with the SARS-CoV-2 virus. Delivered as 2 sequential intramuscular injections (150 mg each of tixagevimab and cilgavimab), a single administration could afford up to 12 months of protection from symptomatic COVID-19 infection, according to the company.
PROVENT, the phase 3, randomized, double-blind, placebo-controlled, multi-center trial, sought to evaluate both the safety and efficacy of AZD7442 compared with placebo, with the primary end point being the first case of any SARS-CoV-2 RT-PCR positive symptomatic illness occurring post-dose prior to day 183.
Unvaccinated adults (> 18 years old) without a prior SARS-CoV-2 infection who may be at risk of either inadequate response to SARS-CoV-2 vaccination or SARS-CoV-2 exposure were eligible to participate. A negative point-of-care SARS-CoV-2 serology test was also required at the time of screening.
A total of 75% of participants had baseline comorbidities or other conditions that placed them at an increased risk for severe COVID-19 if infected, including diabetes, severe obesity, cardiac diseases, chronic obstructive pulmonary disease, chronic kidney, or chronic liver disease. This group also comprised individuals with immunosuppressive disease and those taking immunosuppressive medications.
The average age of participants was 53.5 years, with approximately 43% of them aged 60 or older. About 46.5% were female, 73% were White/Caucasian, 17% were Black/African American, 15% were Hispanic, and 3% were Asian.
Ultimately, a total of 5197 participants in 87 sites across the United States, UK, Spain, France, and Belgium were randomized 2:1 to either 300 mg of AZD7442 (n = 3460) or saline placebo (n = 1737). In the primary efficacy analysis (n = 5172), the risk of developing symptomatic COVID‑19 was reduced by 77% with AZD7442 (95% CI 46.0, 90.0) vs placebo (P < .001).
No cases of severe COVID-19 or COVID-19–related deaths were reported in the study drug arm; in the placebo group, investigators reported 1 case of severe/critical COVID-19 and 2 COVID-19–related deaths. The treatment was well-tolerated, and adverse events were balanced across both groups administered AZD7442 and placebo, occurring in 35% and 34%, respectively. A total of 2.4% and 2.1% of participants experienced injection site reactions in the AZD7442 and placebo arms, respectively.
“The PROVENT data show that 1 dose of AZD7442, delivered in a convenient intramuscular form, can quickly and effectively prevent symptomatic COVID-19,” Myron J. Levin, MD, professor of pediatrics and medicine at the University of Colorado School of Medicine, and principal investigator on the trial, said in a statement. “With these exciting results, AZD7442 could be an important tool in our arsenal to help people who may need more than a vaccine to return to their normal lives.”
The study, “PROVENT: Phase 3 study of efficacy and safety of AZD7442 (tixagevimab/cilgavimab) for pre-exposure prophylaxis of COVID-19 in adults,” was presented virtually at IDWeek 2021, held September 29-October 3, 2021.