FDA Approves Xocova for COVID-19 Post-Exposure Prophylaxis

The FDA approved ensitrelvir (Xocova, Shionogi) for post-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in adults and adolescents aged 12 years and older following contact with an individual who has COVID-19. Shionogi said the approval provides the first oral option in the US therapeutic landscape to help prevent COVID-19 after exposure.

The approval was supported by SCORPIO-PEP, a global, double-blind, randomized, placebo-controlled phase 3 trial evaluating ensitrelvir in household contacts of patients with COVID-19. Participants were at least 12 years old, had a negative local SARS-CoV-2 test, had no COVID-19 symptoms at enrollment, and began treatment within 72 hours after symptom onset in the infected household member.

In the modified intention-to-treat population, confirmed symptomatic COVID-19 occurred by day 10 in 2.9% of participants who received ensitrelvir compared with 9.0% of those who received placebo, corresponding to a risk ratio of 0.33 (P<0.001). Adverse events occurred in 15.1% of participants in the ensitrelvir group and 15.5% in the placebo group, and serious adverse events occurred in 0.2% of participants in each group. No COVID-19–related hospitalizations or deaths were reported.

Xocova is administered as a 5-day oral regimen, with 375mg on day 1 followed by 125mg once daily on days 2 through 5. The prescribing information includes contraindications for several medicines because of potential serious or life-threatening drug interactions. Shionogi said the most common side effects include headache, diarrhea, and cough.

Sources: 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

Hayden FG, Shinkai M, Clark TW, et al; SCORPIO-PEP Study Team. Ensitrelvir for Covid-19 postexposure prophylaxis in household contacts. N Engl J Med. 2026;394(19):1905-1915. doi:10.1056/NEJMoa2509306