FDA Approves Oral Antiviral to Prevent COVID-19 After Exposure

The FDA approved the oral antiviral agent ensitrelvir (Xocova) to help prevent COVID-19 in people ages 12 years or older who were exposed to the SARS-CoV-2 virus, drugmaker Shionogi announced.

Ensitrelvir is a SARS-CoV-2 main protease inhibitor also approved in Japan as COVID-19 postexposure prophylaxis (PEP) and as a treatment for mild to moderate COVID. The drug is not approved to treat COVID-19 in the U.S.

The FDA’s decision was based on the phase III SCORPIO-PEP trial, which showed the risk of getting sick from a household contact with COVID-19 dropped by more than half among those who took ensitrelvir compared with placebo.

In a modified intention-to-treat (ITT) population of a COVID patient’s household contacts, 2.9% of those who took at least one dose of oral ensitrelvir PEP developed COVID within 10 days compared with 9% of those receiving placebo (P<0.001). In SCORPIO-PEP's full ITT population, 4.4% of ensitrelvir patients developed COVID by that point compared with 10.2% of the placebo group (P<0.001).

Ensitrelvir “provides an important new approach to preventing COVID-19, which continues to impact lives,” SCORPIO-PEP investigator Frederick Hayden, MD, of the University of Virginia in Charlottesville, said in a statement. “It could be useful not only in household settings but also in other exposure circumstances, such as outbreaks in nursing homes, chronic or acute care facilities, and following travel-related exposures.”

Patients in the ensitrelvir and placebo groups saw similar adverse event rates (15.1% vs 15.5%) in the phase III trial. The most common events occurring in at least 1% of those taking ensitrelvir and at a greater frequency compared with placebo were headache, diarrhea, and cough. There were no reports of altered taste attributed to ensitrelvir in the trial.

Ensitrelvir should be started within 72 hours of contact with someone who has COVID. The antiviral’s 5-day regimen begins with three 125-mg tablets taken on day 1 and one 125-mg tablet taken on days 2 through 5.

Ensitrelvir should not be taken with drugs that are primarily metabolized by CYP3A. Pregnant women and females of reproductive potential should be advised that ensitrelvir may cause fetal harm. Breastfeeding should be stopped during treatment and for 2 weeks after the final ensitrelvir dose.