A pooled analysis from the global SCORPIO clinical program showed potent antiviral activity with ensitrelvir across age, vaccination status and risk for severe disease
New data underscores that even mild-to-moderate COVID-19 may worsen and exacerbate underlying chronic conditions, supporting the importance of prevention
OSAKA, Japan--(BUSINESS WIRE)--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
Exploratory SCORPIO-PEP Analyses Describe Symptom Severity and Viral Outcomes Among Participants with Breakthrough Infection or Infection Present at Baseline
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.”
Pooled Phase 3 Study Data Analysis Shows Potent Antiviral Activity of Ensitrelvir Through Observed Reductions in Infectious Virus
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 TCID
50
/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.”
Systematic Literature Review Highlights the Continued Burden of COVID-19 and Its Impact on Underlying Chronic Conditions
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.”
The Ongoing Impact of COVID-19
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
About SCORPIO-PEP
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.*
About XOCOVA
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.
U.S. INDICATION
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.
IMPORTANT SAFETY INFORMATION
Do not take XOCOVA if you are:
allergic to ensitrelvir or any of the ingredients in XOCOVA.
take any of the following medicines, as these may interact with XOCOVA and may cause severe or life-threatening side effects or death: apalutamide, carbamazepine, colchicine, dihydroergotamine, enzalutamide, eplerenone, ergotamine, finerenone, ivabradine, lomitapide, lumacaftor/ivacaftor, lurasidone, methylergonovine, phenytoin, pimozide, quinidine, rifampin, St. John’s wort, simvastatin, triazolam or voclosporin.
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.
Before taking XOCOVA, tell your HCP about all your medical conditions, including if you:
are pregnant or plan to become pregnant. XOCOVA may harm your unborn baby. For females who are able to become pregnant, your HCP will check with you to see if you are pregnant before starting XOCOVA. Use effective birth control (contraception) during XOCOVA use and for 2 weeks after the final dose. Tell your HCP right away if you become pregnant or think you may be pregnant during XOCOVA use.
are breastfeeding or plan to breastfeed. It is not known if XOCOVA passes into your breast milk. Do not breastfeed during XOCOVA use and for 2 weeks after the final dose.
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.
What are the possible side effects of XOCOVA?
XOCOVA may cause serious side effects, including:
Allergic reactions, including severe allergic reactions (anaphylaxis).
Stop taking XOCOVA and get medical help right away if you get any of the following allergic reaction symptoms: skin rash; hives; itching; swelling of the mouth, lips, tongue, or face; trouble swallowing or breathing; throat tightness; dizziness or feeling lightheaded; stomach-area (abdomen) pain; or vomiting.
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
or call 1-800-FDA-1088
.
Please see full
Prescribing Information
, including
Patient Information
, for XOCOVA.
About Shionogi Inc.
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
.
About Shionogi & Co., Ltd.
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
.
Forward-Looking Statements
This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, lack of availability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise.
*
Literature search conducted in May 2026
References
1
XOCOVA (ensitrelvir) Prescribing Information. Available from:
. Accessed July 6, 2026.
2
Hayden FG, Shinkai M, et al. Ensitrelvir for COVID-19 postexposure prophylaxis in household contacts.
N Engl J Med
. 2026;394(19):1905-1915. doi:
10.1056/NEJMoa2509306
.
3
Hayden FG, Shinkai M, Clark TW, et al. Ensitrelvir for COVID-19 postexposure prophylaxis in household contacts. Supplementary Appendix.
N Engl J Med
. 2026;394(19). Available from:
.
4
Fukushi A, Nobori H, Sakaguchi H, et al. Early Pre-Symptomatic Treatment with Ensitrelvir Among PCR-Positive, SARS-CoV-2-Exposed and Infected Household Contacts: SCORPIO-PEP Subpopulation Analysis. Presented at: IDWeek 2026; Washington, D.C., United States.
5
Binnicker MJ. Can Testing Predict SARS-CoV-2 Infectivity? The Potential for Certain Methods To Be Surrogates for Replication-Competent Virus.
Journal of Clinical Microbiology
. 2021;59(11):e00469-21. doi:10.1128/JCM.00469-21.
6
Hurt AC, Nobori H, Sakaguchi H, et al. Reduction of Infectious SARS-CoV-2 and Viral RNA with Ensitrelvir: A Pooled Analysis of SCORPIO-SR and SCORPIO-HR Trials [poster presentation]. Presented at: IDWeek 2026; Washington, D.C., United States.
7
Draica F, Verdi D, Fedele M, et al. Impact of Acute COVID-19 on Underlying Chronic Conditions: Systematic Literature Review [poster presentation]. Presented at: IDWeek 2026; Washington, D.C., United States.
8
Baker JM, Nakayama JY, O’Hegarty M, et al. Household transmission of SARS-CoV-2 in five US jurisdictions: comparison of Delta and Omicron variants. PLoS One. 2025;20(1):e0313680. doi:10.1371/journal.pone.0313680.
9
Madewell ZJ, Yang Y, Longini IM Jr, et al. Household secondary attack rates of SARS-CoV-2 by variant and vaccination status: an updated systematic review and meta-analysis. JAMA Netw Open. 2022;5(4):e229317. doi:10.1001/jamanetworkopen.2022.9317.
10
Centers for Disease Control and Prevention [Internet]. Preliminary 2025-2026 COVID-19 burden estimates. Available from:
11
Xie Y, Xu E, et al. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583-590. doi:10.1038/s41591-022-01689-3.
12
Sax PE, Draica F, et al. New onset conditions, exacerbations and worsening of underlying conditions following COVID-19 infection [poster presentation]. Presented at: Conference on Retroviruses and Opportunistic Infections (CROI); 2026; Denver, CO, United States.
13
Graham EL, Clark JR, et al. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized COVID-19 “long haulers.” Ann Clin Transl Neurol. 2021;8(5):1073-1085. doi:10.1002/acn3.51350.
14
Xie Y, Xu E, Bowe B, et al. Risks of mental health outcomes in people with COVID-19: a cohort study. BMJ. 2022;376:e068993. doi:10.1136/bmj-2021-068993.
15
Srivastava S, Garg I. Post-COVID-19 infection: long-term effects on liver and kidneys. World J MetaAnal. 2021;9(3):220-233. doi:10.13105/wjma.v9.i3.220.
16
Tenforde MW, Kim SS, Lindsell CJ, et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March-June 2020. MMWR Morb Mortal Wkly Rep. 2020;69(30):993-998. doi:10.15585/mmwr.mm6930e1.
17
Kwok WC, Chau CH, Tam TCC, et al. Outcomes among patients with chronic obstructive pulmonary disease after recovery from COVID-19 infection of different severity. Sci Rep. 2024;14(1):13881. doi:10.1038/s41598-024-64670-9.
18
Conway SE, Healy BC, Zurawski J, et al. COVID-19 severity is associated with worsened neurological outcomes in multiple sclerosis and related disorders. Mult Scler Relat Disord. 2022;63:103946. doi:10.1016/j.msard.2022.103946.
19
Chen IW, Chang LC, Ho CH, et al. Association between COVID-19 and the development of chronic kidney disease in patients without initial acute kidney injury. Sci Rep. 2025;15(1):10924. doi:10.1038/s41598-025-96032-4.
20
Gravenstein S, Cooke CE, Verdi D, et al. Current impact of COVID-19 in long-term care facilities in the United States: a systematic literature review. Sr Care Pharm. 2026;41(5):167-186. doi:10.4140/TCP.n.2026.167.
Contacts
For Further Information:
SHIONOGI Website Inquiry Form:
U.S. Media:
ShionogiCommunications@shionogi.com
Shionogi Europe Press Office:
pressoffice@shionogi.eu
