COVID Prevention Tx Safe, Shows Efficacy in High-Risk Groups

A monoclonal antibody cocktail designed for COVID-19 pre-exposure prophylaxis was safe, and appeared to be effective across populations at risk of severe COVID and who may have a subpar response to vaccination, a researcher said.

AZD7442 (tixagevimab/cilgavimab) met its primary endpoint, reducing the risk of symptomatic COVID-19 among high-risk populations by 77% (95% CI 46%-90%), though the absolute numbers were small (eight cases in the intervention group vs 17 in the placebo, HR 0.23, 95% CI 0.10-0.53), reported Myron Levin, MD, of the University of Colorado Denver School of Medicine in Aurora.

When stratifying by subgroups, such as older adults and those at high risk for severe COVID, there were numerically fewer cases in the intervention group versus placebo, but the numbers were small, and the confidence intervals were wide.

The treatment also appeared safe, with adverse events (AEs) balanced between groups, and no COVID-19 related deaths in the intervention group, Levin said at a late-breaking presentation at the virtual IDWeek.

Manufacturer AstraZeneca already released topline results of the PROVENT study in August, which showed that the treatment met the primary endpoint, but this presentation included data on subgroups, as well as safety data. It included a median 83 days of follow-up.

In August, FDA authorized an additional dose of mRNA vaccine for certain immunocompromised patients, such as solid organ transplant patients.

Levin noted the treatment would be targeted to individuals with “impaired immune responses and impaired immune function” who not only would be more likely to have severe COVID-19, but less likely to be protected against COVID-19.

“We know from … vaccinology that prevention is always better than treatment if it’s successful,” he said.

Moreover, Levin pointed out that the treatment “successfully neutralized” the Delta variant.

The PROVENT trial was comprised of unvaccinated adults (ages 18 and up) at increased risk of inadequate response to vaccination or COVID-19 infection, who were randomized 2:1 to receive either the treatment or placebo. Overall, 3,460 adults received a single dose, including two intramuscular injections of AZD7442, and 1,737 adults received placebo.

Primary outcome was RT-PCR positive symptomatic illness, according to CDC criteria, which as Levin pointed out, “permits a very low bar for study endpoints to be observed,” since it only requires one symptom.

About 1.4% of participants in the intervention group and 1.3% in the placebo group had at least one serious AE. There were four deaths each in the intervention and placebo groups, including from illicit drug overdose, renal failure, and myocardial infarction. The placebo group had two COVID-19 related deaths from acute respiratory distress syndrome.

Levin said the sample size for some groups was “limiting,” but was consistent across subgroups. For example, adults, ages 60 and up, had three cases of COVID in the intervention group versus six in the placebo (RRR 75.1, 95% CI 0.5-93.8). There were eight cases in the intervention group and 11 in the placebo (RRR 63.6, 9.4-85.4) among adults at high risk for severe COVID.

He described how future research will try to find the “niche” of individuals where the preventive treatment would work best.

“Clearly there are people … who do not respond” to vaccination, Levin said, and the treatment is “designed for people who are not going to respond to the vaccine or lose response early on.”

However, AZD7442 is not meant as a substitute for vaccination, he added.

He added that while the data indicate the treatment was effective for at least 3 months, the data cutoff could underestimate long-term efficacy, as pharmacokinetic modeling predicts the treatment may provide protection for up to 12 months.

IDWeek session moderator Adarsh Bhimraj, MD, of the Cleveland Clinic, spoke about the importance of doing “quality randomized controlled trials” even “in the midst of a raging pandemic.”

“So far we’ve been using COVID therapies and studying them as blunt instruments and not as precision missiles, and hopefully in the future we’ll have better studies,” he said.