Announcement • Jun 02
Shionogi & Co., Ltd. Announces FDA Approval Of XOCOVA For Post-Exposure Prophylaxis Of COVID-19
Shionogi & Co., Ltd. announced that the U.S. Food and Drug Administration (FDA) has approved XOCOVA (ensitrelvir), an oral antiviral, for post-exposure prophylaxis (PEP) of COVID-19 in adults and adolescents 12 years of age and older following contact with an individual who has COVID-19. This approval introduces the first and only oral option to help prevent COVID-19 after exposure in the current therapeutic landscape, addressing a critical gap in prevention. XOCOVA is a five-day oral regimen with three tablets taken on day one and one tablet taken on days two through five. The approval occurred ahead of the Prescription Drug User Fee Act (PDUFA) action date of June 16, 2026. The approval is based on positive results from SCORPIO-PEP, the only Phase 3 study of an oral antiviral to meet the primary endpoint of preventing symptomatic COVID-19 following exposure to an infected individual. XOCOVA significantly reduced the risk of symptomatic COVID-19 by 67% in uninfected individuals following exposure to an infected individual through Day 10 compared with placebo (ensitrelvir n=1,030; placebo n=1,011). Overall, XOCOVA was generally well tolerated, with similar rates of adverse events across groups (15.1% in the XOCOVA group (n=1,190) and 15.5% in the placebo group (n=1,187)). The most common adverse events (regardless of causality) occurring in greater than or equal to 1% of the XOCOVA group and at a greater frequency compared to placebo were headache, diarrhea, and cough. There were no reports of altered taste (dysgeusia) attributed to XOCOVA in the trial. Results from the SCORPIO-PEP trial were published in the New England Journal of Medicine on May 14, 2026. COVID-19 remains highly transmissible, driven by Omicron and its subvariants, and up to 47% of people living with an infected individual may develop COVID-19. The U.S. Centers for Disease and Control estimates that between October 1, 2025 and May 23, 2026 there were 3,800,000–12,400,000 new cases in the U.S., resulting in 800,000–2,300,000 outpatient visits, 120,000–240,000 hospitalizations and 13,000–42,000 deaths. Beyond acute infection, COVID-19 can have lasting impacts. People diagnosed with COVID-19 had increased rates of both new and worsening neurologic, cardiovascular, respiratory, and renal conditions during the year following infection. COVID-19 also disproportionately affects older adults with greater risk for severe illness and death in close-community settings, such as long-term care facilities. The global, double-blind, randomized, placebo-controlled Phase 3 study, SCORPIO-PEP, assessed the safety and efficacy of XOCOVA as post-exposure prophylaxis for COVID-19. The study included 2,387 study participants aged 12 years and older with a negative local screening test for SARS-CoV-2 infection and no symptoms at the time of enrollment, who were exposed to a person living in their household with symptomatic COVID-19. The primary analysis included 2,041 household contact participants with a central laboratory-confirmed negative SARS-CoV-2 test at baseline. The trial was conducted from June 2023–September 2024. More than 99% of household contacts tested positive for antibodies against SARS-CoV-2 N (nucleocapsid) or S (spike) proteins, indicating that nearly all had evidence of previous SARS-CoV-2 infection or vaccination, or both. Study participants were randomly assigned at a 1:1 ratio to receive XOCOVA (375 mg on day 1 and 125 mg on days 2-5) or placebo, once daily, and began treatment within 72 hours of when the household member with COVID-19 began showing symptoms. Participants then continued XOCOVA (125 mg) or placebo for five days. SCORPIO-PEP is the first and only Phase 3 study of an oral antiviral to meet the primary endpoint of preventing COVID-19 following exposure to an infected individual. XOCOVA (ensitrelvir) is a SARS-CoV-2 main protease inhibitor created through joint research between Hokkaido University and Shionogi. SARS-CoV-2 has an enzyme called the main protease, which is essential for the replication of the virus. XOCOVA suppresses the replication of SARS-CoV-2 by selectively inhibiting the main protease. XOCOVA is approved in the U.S. and Japan for post-exposure prophylaxis of COVID-19 in adults and adolescents 12 years of age and older following contact with an individual who has COVID-19. XOCOVA received emergency regulatory approval in Japan in November 2022 and full approval in March 2024 for the treatment of COVID-19 based on results from SCORPIO-SR, a Phase 3 study conducted in Asia during the Omicron-dominant phase of the pandemic. Results from this study were published in JAMA Network Open. XOCOVA is not approved for the treatment of COVID-19 in the U.S.
