Clinical Report: Ensitrelvir Reduced COVID After Household Exposure

Overview

The phase 3 SCORPIO-PEP trial published in The New England Journal of Medicine demonstrated that ensitrelvir significantly reduced the incidence of symptomatic COVID-19 among household contacts exposed to SARS-CoV-2. By day 10, only 3% of participants receiving ensitrelvir developed COVID-19 compared to 9% in the placebo group, indicating a 67% relative risk reduction.

Background

COVID-19, caused by SARS-CoV-2, continues to pose a significant public health challenge. Effective postexposure prophylaxis is crucial for controlling transmission, especially among household contacts. Ensitrelvir is approved in Japan for mild-to-moderate COVID-19 treatment based on findings from the SCORPIO-PEP trial.

Data Highlights

Key Findings

• COVID-19 developed by day 10 in 3% of ensitrelvir recipients vs 9% of placebo recipients.
• Risk ratio of 0.33 indicates a 67% relative risk reduction for symptomatic COVID-19.
• Absolute risk reduction was 6.1 percentage points, with an estimated number needed to treat of 16.
• Among participants with risk factors for severe illness, 9 of 382 ensitrelvir recipients developed COVID-19 compared to 37 of 374 placebo recipients.
• No treatment-emergent variants were detected among placebo recipients.
• Adverse events occurred in 15% of ensitrelvir recipients and 16% of placebo recipients, with no serious adverse events related to treatment.

Clinical Implications

Ensitrelvir may serve as an effective option for postexposure prophylaxis in household contacts of COVID-19 patients. Clinicians should consider its use within 72 hours of exposure to maximize efficacy.

Conclusion

The SCORPIO-PEP trial findings indicate that ensitrelvir reduced symptomatic COVID-19 in household settings.

Related Resources & Content

1. Shionogi, NEJM, 2026 -- Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts
2. FDA, Approval Letter, 2026 -- Approval of Xocova (ensitrelvir) for COVID-19 PEP
3. Infection — Assessment of Ensitrelvir's Effectiveness and Safety in Patients with Asymptomatic or Mild to Moderate COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
4. MDSpire News — FDA Approves Ensitrelvir to Prevent COVID-19 After Exposure
5. MDSpire News — Recent COVID-19 Shot Linked to Less Spread
6. Journal of General Internal Medicine — Effectiveness of Nirmatrelvir/Ritonavir for Outpatients in the Era of Omicron, Vaccination, and Previous Infection: A Meta-analysis
7. COVID-19 Treatment Clinical Care for Outpatients | Covid | CDC
8. IDSA Guidelines on the Treatment and Management of Patients with COVID-19
9. Approval Letter_220442Orig1s000ltr.pdf
10. Zokovea | European Medicines Agency (EMA)
11. Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts | New England Journal of Medicine
12. Oral Nirmatrelvir–Ritonavir as Postexposure Prophylaxis for Covid-19 | New England Journal of Medicine
13. Efficacy and safety of Ensitrelvir in COVID-19 patients: a systematic review and meta-analysis with focus on viral clearance and RNA change - PubMed
14. Approval Label_220442Orig1s000lbl.pdf