COVID Antiviral Can Prevent Household Contacts From Catching Virus

Risk of getting sick from a household contact with COVID-19 dropped by more than half among those who took the antiviral ensitrelvir compared with placebo, a randomized trial showed.

In a modified intention to treat (ITT) population of household contacts of a COVID patient, 2.9% of those who took at least one dose of oral ensitrelvir as postexposure prophylaxis (PEP) developed COVID within 10 days, as compared with 9% of those assigned to placebo (P<0.001), reported researchers led by Frederick Hayden, MD, of the University of Virginia in Charlottesville.

Even in the study’s full ITT population, 4.4% of those randomized to ensitrelvir developed COVID by that point compared with 10.2% of the placebo group (P<0.001), they detailed in the New England Journal of Medicine.

“This is really the first clear demonstration in a well-performed phase III placebo-controlled, double-blind trial that we actually have an agent that is easily administered orally and effective if taken in a timely fashion for protecting individuals who are exposed to COVID-19 in the household setting,” Hayden told MedPage Today.

Beyond households, “the trial results point to likely effectiveness in other settings with COVID-19 outbreaks, such as nursing homes and chronic care facilities,” Hayden said.

Timely PEP with antivirals such as oral oseltamivir (Tamiflu) protects household contacts in influenza cases, he noted, but attempts to duplicate that approach in COVID haven’t succeeded. Clinical trials repurposing COVID treatments nirmatrelvir-ritonavir (Paxlovid) and molnupiravir (Lagevrio) as COVID PEP didn’t deliver significant protection.

Ensitrelvir is approved in Japan as a treatment for mild to moderate COVID and as COVID PEP. The drug’s manufacturer, Shionogi, has submitted the antiviral to the FDA for approval as COVID PEP, with a decision due in June.

The phase III SCORPIO-PEP trial enrolled 2,387 household contacts ages 12 years or older of index patients who developed COVID-19. The study was conducted from June 2023 to September 2024 in Argentina, Japan, South Africa, the U.S., and Vietnam.

The trial included 1,319 index patients with COVID; 83.8% were adults, 56% were female, and most lived in the U.S. (55%) or Japan (39.3%).

The study’s ITT population tested negative for SARS-CoV-2 and was enrolled within 72 hours after an index patient developed COVID symptoms. SCORPIO-PEP’s modified ITT population included 2,041 people who tested negative, were randomized to treatment within 72 hours, and received at least one dose of ensitrelvir or placebo.

The trial’s primary endpoint was lab-confirmed COVID — defined as a positive PCR test and at least one symptom lasting for at least 48 hours — in a household contact within 10 days of receiving ensitrelvir or placebo. Secondary endpoints included lab-confirmed COVID regardless of symptom presence within 10 days.

Among the household contacts in the ITT population, 59.3% were female, mean age was 42.4 years, and 9.3% were age 65 years or older. Most of the study’s household contacts (71.1%) enrolled within 48 hours after an index patient’s symptoms began, and more than a third (37%) had risk factors for severe COVID, including obesity, smoking, or older age. More than 98% of household contacts tested positive for SARS-CoV-2 antibodies, indicating prior infection or vaccination.

Lab-confirmed COVID-19 infections with or without symptoms happened in 14% of household contacts who had at least one dose of ensitrelvir and 21.5% of those who took placebo by day 10. Even in those who developed COVID during PEP, viral loads were lower in those taking ensitrelvir than those on placebo.

Adverse event rates were similar between the ensitrelvir and placebo groups (15.1% vs 15.5%). Unlike nirmatrelvir-ritonavir, those on ensitrelvir weren’t more likely than placebo patients to experience a distorted sense of taste or gastrointestinal side effects.

Hayden cautioned that the study excluded pregnant women, and that ensitrelvir is a moderately strong cytochrome P450 3A inhibitor with potential for drug-drug interactions. Other study limitations included failure to measure practices such as masking that can influence household transmission. Use of antiviral therapy by 18.7% of index patients may have cut the risk of transmission.