Ensitrelvir Fumaric Acid in Patients with SARS-CoV-2: A Retrospective Chart Review

IntroductionAntivirals with differing mechanisms of action are needed for COVID-19 treatment; remdesivir is mainly used in hospitalized patients, but additional antivirals are needed in this setting. Ensitrelvir, a 3C-like protease inhibitor, received emergency approval in Japan in November 2022, based on evidence of rapid symptom resolution in non-hospitalized patients, but confirmation of its efficacy in hospitalized patients is lacking. Case presentationsThis case series reports outcomes for all patients who received ensitrelvir whilst hospitalized with SARS-CoV-2 infection at Rinku General Medical Center, Japan (November 2022- April 2023). Thirty-two hospitalized patients received five days of ensitrelvir treatment (375/125 mg). Mean age was 73.5 years and most patients had mild COVID-19. Patients exhibited various underlying diseases, most commonly hypertension (78.1%) and chronic kidney disease (25.0%). Seven (21.9%) patients were on hemodialysis. The most common concomitant medications were antihypertensives (59.4%) and corticosteroids (31.2%); two (6.3%) patients were being treated with rituximab; 27 (84.4%) patients had viral persistence following pre-treatment remdesivir failure. Following ensitrelvir treatment, all patients experienced clinical improvement as assessed by the investigator. No ICU admissions or deaths due to COVID-19 occurred. Viral clearance was recorded in 18 (56.3%) patients by day 5 and 25 (78.1%) patients at final measurement. No new safety signals were observed. DiscussionThis case series represents ensitrelvir clinical efficacy in hospitalized patients with SARS-CoV-2 in a real-world setting. Most patients experienced persistent viral shedding despite pre-treatment with antivirals, and most were considered high-risk due to underlying conditions. Despite this, no patients experienced progression of COVID-19 to severe or critical disease, including those who failed prior remdesivir treatment. The antiviral activity of ensitrelvir demonstrated here indicates it is a viable treatment option for SARS-CoV-2 infection in this setting. ConclusionEnsitrelvir was associated with potent antiviral activity and positive clinical outcomes in high-risk, hospitalized patients with various comorbidities. Trial RegistrationUMIN000051300 Key Summary PointsO_ST_ABSWhy carry out this study?C_ST_ABSO_LIReal-world evidence of ensitrelvir for the treatment of COVID-19, especially in inpatient settings, is required. C_LIO_LIThis was a retrospective cohort analysis, consisting of 32 high-risk hospitalized patients with a range of disease severities and comorbidities, including patients who had experienced remdesivir treatment failure. C_LI What was learned from the study?O_LIAll patients experienced clinical improvement following ensitrelvir treatment, without any worsening COVID-19. C_LIO_LIViral clearance was documented in 78.1% of patients at final viral measurement. C_LIO_LINo new safety signals of ensitrelvir were observed in this analysis. C_LI