European Commission Approves Shionogi's Zokovea as First Oral COVID-19 Post-Exposure Prophylaxis in the EU
核心洞察
The European Commission granted marketing authorization to Shionogi's Zokovea (搜索) (ensitrelvir) for post-exposure prophylaxis of COVID-19 (搜索) in adults and adolescents aged 12 years and older.
Zokovea (搜索) becomes the first oral antiviral authorized in the EU for COVID-19 (搜索) post-exposure prophylaxis, extending oral antivirals from treatment to prevention after known exposure.
The approval is based on the Phase 3 SCORPIO-PEP trial, in which treatment started within 72 hours of household symptom onset cut symptomatic COVID-19 (搜索) risk by 67% versus placebo.
The European Commission has granted marketing authorization for Zokovea (搜索) (ensitrelvir) for post-exposure prophylaxis (PEP) of COVID-19 (搜索) in adults and adolescents aged 12 years and older, Shionogi announced on September 28, 2026. The decision makes the SARS-CoV-2 main protease (搜索) inhibitor the first oral antiviral medicine authorized in the EU for post-exposure prophylaxis of COVID-19, according to a search of the European Commission Union Register of medicinal products and European Medicines Agency (搜索) records for antivirals authorized for that indication, conducted in August 2026.
The approval adds an oral option for eligible household contacts of people with symptomatic COVID-19 (搜索), aimed at preventing symptomatic infection after exposure. Shionogi positions antiviral medicines alongside vaccines, diagnostics and surveillance as part of a broader set of complementary measures supporting public health preparedness.
A shift in how oral antivirals are used
Matteo Bassetti, Head of the Infectious Diseases Clinic of the Policlinico San Martino University Hospital in Genoa and Full Professor of Infectious Diseases of the University of Genoa, framed the approval as a change in the clinical role of the drug class.
"This approval marks a significant shift in the role of oral antivirals for COVID-19 (搜索): moving from treating patients with confirmed infection to the possibility of early intervention following known exposure to an infected contact, with the aim of preventing symptomatic disease," Bassetti said. "Alongside vaccination, this introduces an additional prevention strategy, expanding the range of tools available to help protect at-risk individuals."
Huw Tippett, CEO of Shionogi Europe, called the European Commission decision "an important regulatory milestone for Shionogi" and said it "reflects the strength of the clinical evidence supporting Zokovea (搜索) for post-exposure prophylaxis of COVID-19 (搜索)." He added that Shionogi "remains committed to advancing innovative medicines for infectious diseases and supporting public health preparedness through scientific innovation."
SCORPIO-PEP: 67% reduction in symptomatic infection
The EC decision is supported by results from SCORPIO-PEP, a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial conducted from June 2023 to September 2024. The study enrolled 2,387 participants aged 12 years and older who had a negative local screening test for SARS-CoV-2 infection and no symptoms at enrollment, and who had been exposed to a person living in their household with symptomatic COVID-19 (搜索). 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 Zokovea (搜索) (375 mg on Day 1 and 125 mg on Days 2 through 5) or placebo, once daily, with treatment beginning within 72 hours of when the household member with COVID-19 (搜索) first showed symptoms.
In the primary analysis population, Zokovea (搜索) significantly reduced the risk of developing symptomatic COVID-19 (搜索) through Day 10 by 67% compared with placebo (Zokovea n=1,030; placebo n=1,011). Shionogi states that SCORPIO-PEP is the first and only Phase 3 study of an oral antiviral to meet the primary endpoint of preventing symptomatic COVID-19 following exposure to an infected individual. Results were published in the New England Journal of Medicine on May 14, 2026.
More than 98% 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.
Tolerability and adverse events
Zokovea (搜索) was generally well tolerated, with similar rates of adverse events across groups: 15.1% in the Zokovea group and 15.5% in the placebo group. The most common adverse events regardless of causality, occurring in at least 1% of the Zokovea group and more frequently than with placebo, were headache, diarrhea and cough.
Mechanism and regulatory footprint
Zokovea (搜索) is a SARS-CoV-2 main protease (搜索) inhibitor created through joint research between Hokkaido University and Shionogi. SARS-CoV-2 relies on the main protease enzyme for replication, and the drug suppresses viral replication by selectively inhibiting that enzyme.
Outside the EU, ensitrelvir is marketed as Xocova in Japan and the United States. It is approved in Japan for the treatment of COVID-19 (搜索) and, in both Japan and the United States, for post-exposure prophylaxis in adults and adolescents aged 12 years and older. Xocova received emergency regulatory approval in Japan in November 2022 and full approval in March 2024 for the treatment of COVID-19, based on the Phase 3 SCORPIO-SR study conducted in Asia during the Omicron-dominant phase of the pandemic; those results were published in JAMA Network Open. In June 2026, Japan granted supplemental approval for pediatric patients aged 6 to under 12 years who weigh at least 20 kg for COVID-19 treatment. The US approval of Xocova for post-exposure prophylaxis came on June 1, 2026.
Following the European Commission approval, Shionogi said a regulatory submission to the UK Medicines and Healthcare products Regulatory Agency (搜索) will follow.