Ensitrelvir Becomes First Oral Option Available in US to Prevent COVID-19

Shionogi Inc has announced US availability of ensitrelvir (Xocova), an oral antiviral now available by prescription as post-exposure prophylaxis (PEP) for COVID-19 in adults and adolescents 12 years and older.¹ Ensitrelvir is the first and only oral option approved in the United States to help prevent COVID-19 following exposure to an infected individual.¹

The drug is dosed as three 125-mg tablets (375 mg) on the first day, followed by one 125-mg tablet once daily on days 2 through 5, and must be started within 72 hours of contact with someone who has COVID-19.¹ Ensitrelvir suppresses SARS-CoV-2 replication by selectively inhibiting the virus's main protease, an enzyme essential to viral replication.¹

"With XOCOVA, we have a novel oral option to help prevent COVID-19 after exposure, and it is available just in time for the annual late summer spike," said Charles Vega, MD, FAAFP, health sciences clinical professor at the University of California, Irvine, School of Medicine. "Taking XOCOVA to help prevent COVID-19 in the critical window between exposure and symptom onset makes sense for anyone who wants to try to avoid illness, and it could be especially beneficial for older adults and individuals with health conditions that may put them at higher risk for severe illness."¹

SCORPIO-PEP trial showed a 67% relative risk reduction in symptomatic COVID-19 after exposure

SCORPIO-PEP, a global, double-blind, randomized, placebo-controlled phase 3 trial, evaluated ensitrelvir as post-exposure prophylaxis in 2387 participants 12 years and older who tested negative for SARS-CoV-2 and had no symptoms at enrollment but had been exposed to a household member with symptomatic COVID-19.² The trial ran from June 2023 to September 2024, and the primary analysis included 2041 household contacts confirmed negative for SARS-CoV-2 at baseline by central laboratory testing.² More than 98% of household contacts tested positive for antibodies against SARS-CoV-2 nucleocapsid or spike proteins at baseline, indicating prior infection, vaccination, or both.²

Participants were randomly assigned 1:1 to receive ensitrelvir or placebo, starting within 72 hours of symptom onset in the household member with COVID-19 and continuing for 5 days.² In the primary analysis population, ensitrelvir reduced the risk of symptomatic COVID-19 through day 10 by 67% compared with placebo (ensitrelvir, n = 1030; placebo, n = 1011).² The most common adverse events occurring in at least 1% of the ensitrelvir group and more frequently than placebo were headache, diarrhea, and cough, and no cases of altered taste were reported in the trial.²

Why Post-Exposure Prophylaxis Matters for This COVID-19 Season

The United States has recorded a summer COVID-19 spike every year since 2020, and early surveillance signals suggest another wave may be building, with CDC scenario modeling indicating the South and West regions, which saw less activity during the most recent fall and winter, may see increased activity this summer.³ Between October 1, 2025, and July 11, 2026, CDC estimated the continuing national burden at 4.2 million to 12.7 million new COVID-19 cases, resulting in 840,000 to 2.3 million outpatient visits, 130,000 to 250,000 hospitalizations, and 14,000 to 42,000 deaths.⁴

Post-exposure prophylaxis has previously been used for influenza, HIV, and other sexually transmitted infections, and ensitrelvir is the first oral option available for this purpose in COVID-19.¹ Ensitrelvir is not approved for the treatment of COVID-19 in the United States, only for prevention following exposure; the drug holds separate approvals for COVID-19 treatment in Japan.¹

"Post-exposure prophylaxis, or PEP for short, has been used successfully with influenza as well as HIV and other sexually transmitted infections, and it has the potential to help reduce the burden of COVID-19," said David Wohl, MD, professor of medicine at the University of North Carolina at Chapel Hill School of Medicine. "The availability of XOCOVA means that now, for the first time, there's an oral option that can help prevent COVID-19 after exposure."¹

Shionogi noted that all components of ensitrelvir, including active pharmaceutical ingredient production, formulation, and packaging, are produced in the United States.¹ The company also offers a copay program for eligible commercially insured patients that can reduce out-of-pocket costs to as little as $0 per prescription fill.¹

References

1. Shionogi Inc. Shionogi Announces U.S. Availability of XOCOVA (ensitrelvir), the First and Only Oral Option to Help Prevent COVID-19 Following Exposure. News release. Published July 28, 2026. Accessed July 28, 2026. https://www.businesswire.com/news/home/20260728842806/en/Shionogi-Announces-U.S.-Availability-of-XOCOVA-ensitrelvir-the-First-and-Only-Oral-Option-to-Help-Prevent-COVID-19-Following-Exposure

2. Hayden FG, Shinkai M, et al. Ensitrelvir for COVID-19 postexposure prophylaxis in household contacts. N Engl J Med. 2026;394(19):1905-1915. doi:10.1056/NEJMoa2509306

3. Centers for Disease Control and Prevention. 2026 COVID-19 Summer Outlook. Accessed July 28, 2026. https://www.cdc.gov/cfa-qualitative-assessments/php/data-research/2026covid-19outlook.html

4. Centers for Disease Control and Prevention. Preliminary estimates of COVID-19 burden for 2024-2025. Accessed July 28, 2026. https://www.cdc.gov/covid/php/surveillance/burden-estimates.html