IDWeek 2026: New Exploratory Analyses Evaluate XOCOVA^® (ensitrelvir) Following COVID-19 Exposure, Including Breakthrough Infections and Infection Present at Baseline

OSAKA, Japan, October 21, 2026 – Shionogi & Co., Ltd. (Head Office: Osaka, Japan; Chief Executive Officer: Isao Teshirogi, Ph.D.; hereafter "Shionogi") will present new exploratory analyses from the global Phase 3 SCORPIO-PEP study, virology data from across the ensitrelvir phase 3 program, and new insights on the continued burden of COVID-19 at IDWeek 2026.

XOCOVA^® (ensitrelvir) was approved in May 2026 by the U.S. Food and Drug Administration (FDA) for post-exposure prophylaxis (PEP) of COVID‑19 in adults and adolescents 12 years of age and older following contact with an individual who has COVID-19.¹ The approval was based on positive results from SCORPIO-PEP, a global, double-blind, randomized, placebo-controlled Phase 3 study.

In the primary analysis population, XOCOVA significantly reduced the risk of developing symptomatic COVID-19 by 67% in individuals following exposure to an infected individual through Day 10 compared with placebo (ensitrelvir n=1,030; placebo n=1,011).^1,2

In SCORPIO-PEP, XOCOVA was generally well tolerated, with similar rates of adverse events across groups (15.1% in the ensitrelvir group (n=1,190) and 15.5% in the placebo group (n=1,187)).² The most common adverse events (regardless of causality) occurring in greater than or equal to 1% of the XOCOVA group and at a greater frequency compared to placebo were headache, diarrhea, and cough.^1,2 There were no reports of altered taste (dysgeusia) attributed to XOCOVA in the trial.^2,3

In an oral presentation at IDWeek 2026, Shionogi will report new exploratory analyses from the SCORPIO-PEP study evaluating participants who had breakthrough infections or were already infected at baseline.⁴

Among breakthrough infection cases (based on RT-PCR positivity regardless of symptoms) in the primary analysis population, the mean maximum viral RNA levels were lower in participants receiving ensitrelvir compared to those receiving placebo (3.1 vs 4.3 mean log10 copies/mL, respectively, seen in 144 and 217 breakthrough infection cases, respectively).⁴ In household contacts who were infected with SARS-CoV-2 at the time of enrollment (confirmed positive by baseline central RT-PCR despite testing negative on a local screening test and being asymptomatic; n=237), numerically lower mean viral RNA levels were also observed with ensitrelvir in comparison to placebo on Days 3 and 6.⁴

In the primary analysis population, a numerically lower proportion of participants with symptomatic breakthrough infections taking ensitrelvir developed severe symptoms, compared with those taking placebo (severe symptoms were reported in 8/28 or 28.6% of individuals receiving ensitrelvir compared with 48/89 or 53.9% of individuals receiving placebo).⁴ Similarly, numerically lower mean total symptom scores earlier in the study and lower mean maximum total symptom scores were observed in participants receiving ensitrelvir compared with placebo (mean maximum total scores were 6.6 vs 8.9 respectively).⁴

In participants receiving ensitrelvir who were infected with SARS-CoV-2 at the time of enrollment despite testing negative on a local screening test and being asymptomatic, a numerically lower proportion developed severe symptoms compared with placebo (severe symptoms were reported in 2/18 or 11.1% of individuals receiving ensitrelvir compared with 9/24 or 37.5% of individuals receiving placebo).⁴ Similarly, numerically lower mean total symptom scores earlier in the study and mean maximum total symptom scores were observed in those receiving ensitrelvir compared with placebo.⁴

“SCORPIO-PEP showed that early administration of ensitrelvir following household exposure reduced the risk of symptomatic COVID-19,” said Simon Portsmouth, MD, FRCP, Senior Vice President, Head of Clinical Development, Shionogi Inc. “This exploratory analysis provides additional insight into the antiviral activity of ensitrelvir on viral load and symptom outcomes among participants who developed COVID-19. These observations add to our understanding of the potential outcomes associated with early administration of ensitrelvir following household exposure.”

In a separate poster presentation, investigators will report findings from a post-hoc pooled analysis of two Phase 3 studies designed to assess infectious-virus-based virologic outcomes across a broad range of participants with confirmed COVID-19 infection.⁶ Unlike viral RNA detection by RT-PCR, which may identify noninfectious viral remnants, infectious-virus measurements assess the presence of replication-competent virus and can provide additional insight into antiviral activity.^5,6

By Day 4, participants who received ensitrelvir (375 mg on Day 1, then 125 mg on Days 2–5; n=484) had numerically greater reductions in infectious virus titers than those who received placebo (n=487) (difference in least-squares mean of 0.21 log10 TCID₅₀/mL).⁶ Similar results were observed across subgroups regardless of age, vaccination status, and risk factors for severe COVID-19. Also on day 4, a higher proportion of ensitrelvir recipients had undetectable infectious viral load compared to those receiving placebo (95.7% [463/484] vs 72.1% [351/487]).⁶

“With data pooled from two Phase 3 studies, this analysis represents the most extensive infectious virus dataset reported for a COVID-19 antiviral to date, and it helps to further characterize ensitrelvir’s effect on active viral replication,” said Florin Draica, MD, CMD, MBA, Senior Vice President, U.S. Medical Affairs, Shionogi Inc. “Although these results are exploratory, the observed reductions in infectious virus provide additional support of ensitrelvir’s antiviral activity and warrant further evaluation of their potential implications for infectivity and transmission.”

Shionogi will also present a systematic literature review evaluating the impact of acute COVID-19 on individuals with underlying chronic conditions during the Omicron era or in earlier time periods. The review included 35 observational studies assessing clinical outcomes, health-related quality of life (HRQoL), and healthcare resource utilization (HCRU).⁷ Across the studies reviewed, acute COVID-19 was associated with worsening, exacerbation, or relapse of underlying chronic conditions spanning respiratory, neurologic, cardiovascular, renal, and other disease areas.⁷

More than half of studies evaluating clinical outcomes (17 out of 33) reported statistically significant worsening of underlying chronic conditions such as asthma, COPD, multiple sclerosis and CKD, following acute COVID-19.⁷ COVID-19 was also associated with worsening outcomes in five of eight studies reporting on HRQoL and increased hospitalization frequency or extended hospital length of stay in four of the six studies reporting on HCRU.⁷

“Across studies in this review, acute COVID-19 during the Omicron predominance was associated with worsening or exacerbation of underlying chronic conditions. Specifically, we found that COVID-19 infection, even mild or moderate, was associated with reduced health-related quality of life and increased healthcare resource utilization,” said Alpesh N. Amin, M.D., Professor, Founding Chief and Executive Director of Hospital Medicine & Palliative Medicine, and Co-Director & Medical Director of the Institute for Precision Health at the University of California, Irvine. “These findings reinforce the continued burden of COVID-19 and underscore the importance of prevention, especially among people living with chronic conditions.”

COVID-19 remains highly transmissible, driven by Omicron and its subvariants, and up to 47% of people living with an infected individual may develop COVID-19.^8,9 The U.S. Centers for Disease Control and Prevention estimates that between October 1, 2025, and September 26, 2026, there were 5.2-14.6 million new cases in the U.S., resulting in 1.1-2.7 million outpatient visits, 170,000-270,000 hospitalizations and 17,000-48,000 deaths.¹⁰

Beyond acute infection, COVID-19, even mild-to-moderate, may worsen underlying chronic conditions and can have lasting health impacts. Studies have reported increased rates of new and worsening neurologic, cardiovascular, respiratory, and chronic kidney conditions in the year following COVID-19 infection.^11–19 COVID-19 also disproportionately affects older adults with greater risk for severe illness and death in close-community settings, such as long-term care facilities.²⁰

The global, double-blind, randomized, placebo-controlled Phase 3 study, SCORPIO-PEP, assessed the safety and efficacy of XOCOVA as post-exposure prophylaxis for COVID-19. The study was conducted from June 2023-September 2024. It included 2,387 study participants aged 12 years and older with a negative local screening test for SARS-CoV-2 infection and no symptoms at the time of enrollment, who were exposed to a person living in their household with symptomatic COVID-19.

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.

Study participants were randomly assigned at a 1:1 ratio to receive XOCOVA (375 mg on Day 1 and 125 mg on Days 2-5) or placebo, once daily for five days, and began treatment within 72 hours of when the household member with COVID-19 began showing symptoms.

Results from SCORPIO-PEP were published in the New England Journal of Medicine. SCORPIO-PEP is the first and only Phase 3 study of an oral antiviral to meet the primary endpoint of preventing COVID-19 following exposure to an infected individual.*

XOCOVA^® (ensitrelvir) is a SARS-CoV-2 main protease inhibitor created through joint research between Hokkaido University and Shionogi. SARS-CoV-2 has an enzyme called the main protease, which is essential for the replication of the virus. XOCOVA suppresses the replication of SARS-CoV-2 by selectively inhibiting the main protease.

XOCOVA is approved in the U.S., Japan and European Union for post-exposure prophylaxis of COVID‑19 in adults and adolescents 12 years of age and older following contact with an individual who has COVID-19.

XOCOVA received emergency regulatory approval in Japan in November 2022 and full approval in March 2024 for the treatment of COVID-19 in adults and adolescents 12 years of age and older. XOCOVA received supplemental approval in Japan in June 2026 for pediatric patients aged 6 to under 12 years who weigh at least 20 kg for the treatment of COVID-19.

XOCOVA is not approved for the treatment of COVID-19 in the U.S.

XOCOVA (ensitrelvir) is a prescription medicine used to help prevent coronavirus disease 2019 (COVID-19) in adults and children aged 12 years and older following contact with a person who has COVID-19 (post-exposure prophylaxis). It is not known if XOCOVA is safe and effective in children under age 12.

These are not the only medicines that may cause serious or life-threatening side effects if taken with XOCOVA. XOCOVA may increase or decrease the levels of many medicines in your body. Tell your healthcare provider (HCP) about all the medicines you take because additional laboratory tests or dose changes of your other medicines may be necessary during XOCOVA use. Your HCP may tell you about specific symptoms to watch for that may indicate you need to stop or decrease the dose of some of your other medicines.

Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your HCP can tell you if it is safe to take XOCOVA with other medicines. Do not start a new medicine without telling your HCP.

The most common side effects of XOCOVA include: headache, diarrhea, and cough.

These are not all possible side effects of XOCOVA. For more info, ask your HCP or pharmacist. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Shionogi Inc. is a U.S. subsidiary of Shionogi & Co., Ltd., a global research‑driven pharmaceutical company. Since 1878, Shionogi has been developing new treatments to improve patients' lives worldwide. Today in North America, we are focused on infectious and rare diseases, and our portfolio includes an antibiotic for serious infections caused by susceptible Gram-negative bacteria, an oral antiviral for post-exposure prophylaxis of COVID-19 and a therapy for amyotrophic lateral sclerosis (ALS). Together with our subsidiaries Qpex Biopharma Inc. and Shionogi Canada Inc., we are continuing to innovate across infectious disease, rare disease and additional high‑need therapeutic areas. Learn more at  shionogi.com.

Shionogi & Co., Ltd. is a 148-year-old global, research-driven pharmaceutical company headquartered in Osaka, Japan, that is dedicated to bringing benefits to patients based on its corporate philosophy of “supplying the best possible medicine to protect the health and wellbeing of the patients we serve.” The company currently markets products in several therapeutic areas including anti-infectives, pain and CNS disorders. Shionogi’s research and development currently targets two therapeutic areas: infectious diseases and diseases with unmet medical needs, including rare diseases, allergy/inflammation, oncology, hearing loss, and sleep apnea. For more information on Shionogi & Co., Ltd., please visit https://www.shionogi.com/global/en.

* Literature search conducted in May 2026

SHIONOGI Website Inquiry Form: https://www.shionogi.com/global/en/contact.html

U.S. Media: ShionogiCommunications@shionogi.com

Shionogi Europe Press Office: pressoffice@shionogi.eu

1. XOCOVA^® (ensitrelvir) Prescribing Information. Available from: https://www.shionogi.com/content/dam/shionogi/si/products/pdf/xocova.pdf. Accessed July 6, 2026.

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