FDA Approval

Ensitrelvir (Xocova) Receives FDA Approval for COVID-19 Post-Exposure Prophylaxis

Anthony Calabro, MA

Key Highlights

  • Ensitrelvir (Xocova), an oral antiviral, was approved for post-exposure prophylaxis of COVID-19 in adults and adolescents aged 12 years and older after contact with an individual who has COVID-19.
  • Approval was based on SCORPIO-PEP, a global, double-blind, randomized, placebo-controlled phase 3 study.
  • Ensitrelvir reduced the risk of symptomatic COVID-19 by 67% through day 10 compared with placebo in uninfected individuals following exposure.
  • Adverse event rates were 15.1% with ensitrelvir and 15.5% with placebo; the most common adverse events occurring in at least 1% of the ensitrelvir group and more frequently than placebo were headache, diarrhea, and cough.

On June 1, 2026, the FDA approved ensitrelvir (Xocova, Shionogi), an oral antiviral, for post-exposure prophylaxis of COVID-19 in adults and adolescents aged 12 years and older following contact with an individual who has COVID-19. Ensitrelvir is approved in the United States and Japan.

The approval was supported by SCORPIO-PEP, a global, double-blind, randomized, placebo-controlled phase 3 study evaluating the safety and efficacy of ensitrelvir as post-exposure prophylaxis for COVID-19. The study included 2,387 participants aged 12 years and older with a negative local screening test for SARS-CoV-2 infection and no symptoms at enrollment who had been exposed to a household member with symptomatic COVID-19. The primary analysis included 2,041 household contacts with a central laboratory-confirmed negative SARS-CoV-2 test at baseline.

Participants were randomly assigned 1:1 to receive ensitrelvir or placebo once daily, and treatment began within 72 hours of symptom onset in the household of the member with COVID-19. Ensitrelvir reduced the risk of symptomatic COVID-19 by 67% through day 10 compared with placebo among uninfected individuals following exposure (ensitrelvir, n = 1,030; placebo, n = 1,011). The trial was conducted from June 2023 to September 2024, and more than 99% of household contacts had antibodies against SARS-CoV-2 nucleocapsid or spike proteins.

“Ensitrelvir inhibits viral replication, helping protect people who have been exposed to COVID-19 from developing illness,” Frederick Hayden, MD, Richardson Professor Emeritus of Clinical Virology and Professor Emeritus of Medicine, University of Virginia School of Medicine, said in a press release.

Overall adverse event rates were similar between groups, occurring in 15.1% of participants receiving ensitrelvir (n = 1,190) and 15.5% of participants receiving placebo (n = 1,187). The most common adverse events, regardless of causality, occurring in at least 1% of the ensitrelvir group and more frequently than in the placebo group were headache, diarrhea, and cough. No reports of altered taste, or dysgeusia, were attributed to Xocova in the trial.

The recommended regimen is 5 days of oral treatment: 3 tablets on day 1 followed by 1 tablet daily on days 2 through 5. In SCORPIO-PEP, participants received ensitrelvir 375 mg on day 1 and 125 mg on days 2 through 5.

Reference
Shionogi & Co, Ltd. Shionogi announces FDA approval of Xocova (ensitrelvir), the first and only oral option to help prevent COVID-19 following exposure. Published June 1, 2026. Accessed June 23, 2026. https://www.shionogi.com/global/en/news/2026/06/20260601,2.html