Introduction: Ensitrelvir fumaric acid (ensitrelvir) is an orally active 3C-like protease inhibitor used to treat severe acute respiratory syndrome coronavirus 2 infection. Ensitrelvir was granted an emergency use authorization in Japan in 2022, but reports on the effectiveness and safety of ensitrelvir in actual clinical settings are limited. Methods: Here, we report a case series of 9 patients with laboratory-confirmed symptomatic coronavirus disease of 2019 (COVID-19) who completed a 5-day course of ensitrelvir at Tomita Hospital from November 2022 to April 2023. Data on clinical symptoms, oxygen saturation, and food intake were collected for 14 days, beginning on the first day of ensitrelvir administration. The outcome of COVID-19 in each patient was also evaluated during this period. Results: All patients were female, 80 years old or older, and the mean age was 90.2 ± 5.5 years. All patients received ensitrelvir within 2 days after the onset of COVID-19. At baseline, 7 among the 9 patients had their body temperature above 37.5 °C and all of them had oxygen saturation levels of 94% or higher. All patients recovered without worsening of COVID-19, and none received oxygen or additional antiviral drugs during the observation period; no deaths were reported within 14 days. After receiving ensitrelvir for 5 days, all patients had resolution of fever (<37 °C). There was no significant decrease in food intake of patients due to COVID-19. All patients maintained oxygen saturation above 93%. Conclusion: Our results provide information on the real-world usage of ensitrelvir in elderly, hospitalized patients with COVID-19, and suggests that ensitrelvir is an option for treatment of COVID-19 in these population.

A single oral dose of baloxavir marboxil, a cap-dependent endonuclease inhibitor, is approved for patients with influenza A or B infection; however, real-world evidence is limited. We evaluated the effectiveness of baloxavir vs neuraminidase inhibitors in reducing the incidence of severe illness in influenza outpatients aged 5-11 years. In this retrospective cohort study, we analyzed individual-level data from patients treated with these antivirals, using a large, Japanese health insurance claims database (JMDC). Patients were included at the first date of diagnosis of the influenza virus infection (Day 1) in two influenza seasons. The primary outcome was the incidence of hospitalization from Day 2-14. Of 196,749 included patients (Season 2018/2019, n = 103,709; Season 2019/2020, n = 93,040), 20.9 % received baloxavir, 38.8 % received oseltamivir, 28.7 % received laninamivir, and 11.6 % received zanamivir. In each treatment group, 61-70 % patients had influenza A. The incidence of hospitalization from Day 2-14 was significantly lower for baloxavir than for oseltamivir, laninamivir, and zanamivir. The adjusted risk ratio (95 % CI) for oseltamivir, laninamivir, and zanamivir were 1.86 (1.30-2.68), 2.11 (1.37-3.25), and 1.90 (1.31-2.77), respectively, compared with baloxavir. Comparative incidence of hospitalizations between agents were unaffected by season or virus type. Using a large, Japanese health insurance claims database, a lower rate of hospitalization was demonstrated in children aged 5-11 years with an influenza virus infection when treated with baloxavir vs neuraminidase inhibitors. Thus, single dose, oral baloxavir may reduce the incidence of severe illness in these patients.

Introduction Influenza is a highly transmissible respiratory viral infection, with a risk of severe complications and excess respiratory mortality. Clinical trial data showed that baloxavir was more effective than oseltamivir for reducing duration of virus shedding, which is a key predictor of transmission. Consideration of the effect of treatments on transmission rates is important to ensure that the value of treatments is captured. This study assessed the cost-effectiveness of different treatment strategies with baloxavir and oseltamivir, considering their impact on influenza transmission. Methods The analysis used two models: a dynamic transmission model to estimate influenza incidence, with outputs incorporated in a static population-level decision tree model, in order to evaluate the clinical outcomes and cost-effectiveness of treatment strategies with different shares of baloxavir and oseltamivir from the healthcare payer’s perspective in Japan. Clinical data were sourced from phase 3 trials, and cost inputs were informed by the Ministry of Health, Labour and Welfare, as well as JammNet. Sensitivity and scenario analyses were also conducted. Results Increasing the use of baloxavir in adults from 40% to 50% reduces the number of influenza cases by 17%, hospitalizations by 18%, and deaths by 23%, with cost savings of JPY (Japanese yen) 16,280 million and 10,486 quality-adjusted life years (QALYs) gained, in the total population in Japan. Across all risk and age subgroups, increasing the share of baloxavir was cost-saving and more effective, and, therefore, was considered dominant, which was also confirmed by the sensitivity analysis. Conclusion Treatment of influenza with baloxavir is anticipated to offer value for money within Japan’s healthcare system, delivering significant clinical benefits both for the general population and for all age and risk groups. Accounting for the treatment’s impact on influenza transmission adds another dimension of value and further reinforces the evidence supporting the growing use of baloxavir in Japan.

Recurrent outbreaks of coronavirus disease 2019 (COVID-19) in Japan highlight the continued need for effective prevention, particularly household transmission. This study clarifies the epidemiological profile of household transmission of COVID-19 and influenza by quantifying transmission rates according to demographic and relational characteristics. An anonymized health insurance claims database was used to identify index patients diagnosed with COVID-19 or influenza between November 2021 and August 2023. Transmission events were defined as cases in which household members were diagnosed with the same infection in the week following the index patient’s diagnosis (Day 1). Analyses were stratified by the age of the index patients and age-based transmission patterns between index patients and household members. A total of 1,001,509 index patients with COVID-19 and 207,090 with influenza met the inclusion criteria. Transmission rates were highest among index patients aged <12 years (COVID-19, 40.17%; influenza, 33.51%). Transmission from children was disproportionately high, while age-combination analysis demonstrated elevated transmission both from and to children for both diseases. COVID-19 exhibited increased transmission among adults. As the primary drivers of household transmission for both COVID-19 and influenza, preventive strategies should be tailored to children. COVID-19 interventions must also address transmission among adults to strengthen household-level infection control.

Introduction Mathematical modeling can provide quantitative understanding of the viral dynamics and viral reduction effects of drugs and enable simulations of the dynamics in various scenarios. In this study, a drug effect model of ensitrelvir was developed to describe the viral reduction effect. Using the model, we also estimated the impact of treatment with ensitrelvir on the reduction in the number of infected patients at the population level in Japan. Methods The drug effect model of ensitrelvir was developed based on a viral dynamic model for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a population pharmacokinetic model of ensitrelvir using 10,477 samples of viral load from 1447 patients with coronavirus disease 2019 (COVID-19) in a phase 2/3 study. It was assumed that the drug effect on SARS-CoV-2 promoted the viral clearance depending on the free plasma concentrations. We estimated the impact of ensitrelvir treatment on the reduction in the number of infected patients at the population level in Japan using the susceptible–infectious–recovered–susceptible (SIRS) model including transmission mitigation. Results The viral reduction effect of ensitrelvir was characterized as a promotion of viral clearance depending on the plasma ensitrelvir concentrations using the E_max model. The maximum reduction effect was considered to depend on the time from symptom onset to treatment. The maximum transmission mitigation effect was observed when treatment was initiated within 12–24 h of symptom onset, and secondary infections could be reduced by administering ensitrelvir as soon as possible after symptom onset. Conclusion The viral reduction by ensitrelvir could be characterized based on the viral dynamics, and the dynamics could be estimated using the drug effect model. Furthermore, the drug effect on population level transmission based on the dynamics could be estimated. Thus, the simulation could be conducted for various conditions.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic highlighted the need for real-world evidence on treatment effectiveness and postinfection outcomes. In Japan, comprehensive prospective real-world data remain limited, particularly for oral antiviral treatments and post-COVID-19 conditions. This nationwide registry and cohort study aims to prospectively collect data on COVID-19 patients to address this gap and to evaluate treatment effectiveness and outcomes using cohort analyses. Methods and analysis: This large-scale, prospective registry-based cohort study will be conducted at acute care hospitals across Japan and will enroll COVID-19 outpatients and inpatients aged ≥ 12 years with symptom onset within 5 days prior to consent. The study will establish a comprehensive COVID-19 registry and will concurrently serve as a cohort study to assess treatment patterns, effectiveness, and clinical outcomes. Outcome measures, broadly defined for the overall study population, will be collected from electronic health records and patient-reported outcomes via an electronic PRO system at baseline, Day 28, and Day 84. Outcomes include patient characteristics, acute-phase and post-infection symptoms, treatment patterns, clinical outcomes (including severe events), healthcare utilization, work productivity and activity impairment, and safety of anti-severe acute respiratory syndrome coronavirus 2 drugs. However, an interim analysis showed lower-than-expected enrollment, which resulted in insufficient statistical power to assess severe outcomes. To increase statistical power and ensure that the study can evaluate severe outcomes as originally intended, the registration period has been extended to October 31, 2025. Summary statistics will be calculated for all outcome measures, and detailed analysis methods will be prespecified in a separate statistical analysis plan.