Study design
SCORPIO-PEP: The first oral antiviral trial to meet the primary endpoint of preventing symptomatic* COVID-19 after exposure1-4
SCORPIO-PEP was a randomized, double-blind, placebo-controlled, multinational Phase 3 trial conducted in 5 countries evaluating XOCOVA in asymptomatic standard- or high-risk participants 12 years of age or older considered not to have SARS-CoV-2 infection.1,5
2387 participants were randomized 1:1 to receive either XOCOVA or placebo for 5 days, then subsequently tested through Day 281,5†
*Defined as central-laboratory–confirmed RT-PCR positivity of SARS-CoV-2 and ≥1 of the 14 COVID-19 symptoms lasting ≥48 hours.5
†Nasopharyngeal swabs were collected on Days 1, 3, 6, 10, 15, 21, and 28 for RT-PCR testing of participants taking XOCOVA or placebo.5
Criteria for symptomatic COVID-19
Defined as central-laboratory–confirmed RT-PCR positivity of SARS-CoV-2 and ≥1 of the following 14 prespecified COVID-19 symptoms lasting ≥48 hours5,6:
- 1.Fever
- 2.Shortness of breath or difficulty breathing
- 3.Cough
- 4.Sore throat
- 5.Nasal congestion or runny nose
- 6.Chills
- 7.Fatigue
- 8.Body or muscle pain or aches
- 9.Headache
- 10.Nausea
- 11.Vomiting
- 12.Diarrhea
- 13.Change in sense of taste
- 14.Change in sense of smell
XOCOVA was studied in a broad range of patients5
Baseline characteristics were similar in the XOCOVA and placebo groups5
Baseline characteristics (mITT population)5,6
| Characteristic | XOCOVA(n=1030) | Placebo(n=1011) |
|---|---|---|
| Age—yr, mean (SD) | 41.8 (16.9) | 43.0 (16.1) |
| ≥65, n (%) | 99 (9.6) | 90 (8.9) |
| Female, n (%) | 584 (56.7) | 627 (62.0) |
| BMI—kg/m2, mean (SD) | 26.4 (5.7) | 26.6 (5.3) |
| Hispanic or Latino, n (%)‡ | 620 (60.2) | 623 (61.6) |
| Race, n (%)‡ | ||
| White | 632 (61.4) | 615 (60.8) |
| Black or African American | 51 (5.0) | 56 (5.5) |
| Asian | 325 (31.6) | 321 (31.8) |
| American Indian or Alaska Native | 2 (0.2) | 4 (0.4) |
| Other | 20 (1.9) | 15 (1.5) |
| Risk status, n (%) | ||
| High risk§ | 382 (37.1) | 374 (37.0) |
| Non-high risk | 648 (62.9) | 637 (63.0) |
| Hours from symptom onset in the CP to enrollment of SP, n (%) | ||
| <48 | 732 (71.1) | 720 (71.2) |
| Geographic region, n (%) | ||
| US | 692 (67.2) | 683 (67.6) |
| South America | 7 (0.7) | 4 (0.4) |
| Africa | 6 (0.6) | 5 (0.5) |
| Asia (except Japan) | 59 (5.7) | 49 (4.8) |
| Japan | 266 (25.8) | 270 (26.7) |
| Positive baseline serology, n (%)|| | ||
| S-antibody | 1018 (99.4) | 1004 (99.7) |
| N-antibody | 1002 (97.9) | 985 (98.0) |
‡Race and ethnic group were reported by the participant.5
§Some high-risk factors for severe illness are obesity, cardiovascular disease, chronic lung disease, chronic kidney disease, chronic liver disease, Down syndrome, sickle-cell disease, immunocompromised conditions or treatment for immunocompromised conditions, dementia, diabetes mellitus, smoking, and history of stroke or cerebrovascular disease.5
||Percentages are based on the number of HHCs in the mITT analysis set who had definitive test results at screening Day 1, within each treatment group and overall. Number of HHCs with no missing serology data was used as denominator.6
BMI=body mass index; CP=COVID-positive patient; HHC=household contact; ITT=intention-to-treat; mITT=modified intention-to-treat; PEP=post-exposure prophylaxis; R=randomization; RT-PCR=reverse transcription polymerase chain reaction; SD=standard deviation; SP=study participant.
Review the study results of early intervention against COVID-19 after exposure
INDICATION & IMPORTANT SAFETY INFORMATION
INDICATION
XOCOVA (ensitrelvir) is indicated for post-exposure prophylaxis (PEP) of coronavirus disease 2019 (COVID-19) in adults and adolescents 12 years of age and older following contact with an individual who has COVID-19.
IMPORTANT SAFETY INFORMATION
Contraindications
XOCOVA is contraindicated in patients with a history of clinically significant hypersensitivity reactions to XOCOVA or any of its components. XOCOVA is also contraindicated when administered with drugs primarily metabolized by CYP3A for which elevated concentrations may be associated with serious and/or life-threatening reactions or when administered with strong CYP3A inducers because they may significantly reduce XOCOVA plasma concentrations leading to potential loss of virologic response.
Embryofetal Toxicity
Based on animal data, XOCOVA may cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential that XOCOVA may cause fetal harm. Verify pregnancy status of females of reproductive potential before initiating XOCOVA and advise using effective contraception during XOCOVA use and for 2 weeks after the final dose.
Risk of Serious Adverse Reactions Due to Drug Interactions
XOCOVA is a strong CYP3A inhibitor and an inhibitor of P-gp and BCRP. In patients receiving or initiating medications metabolized by CYP3A or transported by P-gp or BCRP, XOCOVA may increase plasma concentrations of those medications and may potentially lead to severe, life-threatening, or fatal events from increased exposure. CYP3A inducers may decrease concentrations of XOCOVA, leading to loss of therapeutic effect.
Before prescribing XOCOVA, review all concomitant medications to assess potential drug-drug interactions and determine if those medications require a dose adjustment, interruption, and/or additional monitoring. Consider the benefit of XOCOVA and whether risk of potential drug-drug interactions can be managed.
Hypersensitivity Reactions Including Anaphylaxis
Hypersensitivity reactions, including anaphylaxis, anaphylactic shock, and angioedema have been reported. If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue XOCOVA and initiate appropriate treatment.
Lactation
There are no data on the presence of XOCOVA in human milk, effects on breastfed infants, or effects on milk production. XOCOVA was present in the milk of lactating rats. Advise women not to breastfeed while on XOCOVA and for 2 weeks after the final dose.
Adverse Reactions
The most common adverse events occurring in ≥1% of XOCOVA patients and at greater frequency than placebo, respectively, were headache (2.9% vs 2.6%), diarrhea (1.7% vs 1.3%), and cough (1.1% vs 0.6%).
Laboratory Abnormalities
Asymptomatic hemoglobin declines from baseline of >2 g/dL occurred in XOCOVA and placebo patients (3% vs 1%, respectively).
Please see full Prescribing Information.
References: 1. XOCOVA [package insert]. Florham Park, NJ: Shionogi Inc. 2. U.S. Centers for Disease Control and Prevention. Updated February 5, 2026. Accessed April 21, 2026. https://www.cdc.gov/covid/treatment/index.html 3. Hammond J, Yunis C, Fountaine RJ, et al. Oral nirmatrelvir-ritonavir as postexposure prophylaxis for Covid-19. N Engl Med. 2024;391(3):224-234. 4. Alpizar SA, Accini J, Anderson DC, et al. Molnupiravir for intra-household prevention of COVID-19: the MOVe-AHEAD randomized, placebo-controlled trial. J Infect. 2023;87(5):392-402. 5. Hayden FG, Shinkai M, Clark TW, et al. Ensitrelvir for Covid-19 postexposure prophylaxis in household contacts. N Engl J Med. 2026;394(19):1905-1915. 6. Hayden FG, Shinkai M, Clark TW, et al. Ensitrelvir for Covid-19 postexposure prophylaxis in household contacts. N Engl J Med. 2026;394(19):1905-1915. Supplemental appendix. Accessed May 29, 2026. https://www.nejm.org/doi/suppl/10.1056/NEJMoa2509306/suppl_file/nejmoa2509306_appendix.pdf