Ensitrelvir Fumaric Acid in Patients with SARS-CoV-2: A Retrospective Chart Review
Authors: Yamato Masaya , Kinoshita Masahiro , Miyazawa Shogo , Seki Masayuki , Mizuno Tomoki , Sonoyama Takuhiro 
Published: September 2023

Introduction

Antivirals 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 presentations

This 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.

Discussion

This 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.

Conclusion

Ensitrelvir was associated with potent antiviral activity and positive clinical outcomes in high-risk, hospitalized patients with various comorbidities.

Trial Registration

UMIN000051300

Key Summary Points

Why carry out this study?

Real-world evidence of ensitrelvir for the treatment of COVID-19, especially in inpatient settings, is required.

This 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.

What was learned from the study?

All patients experienced clinical improvement following ensitrelvir treatment, without any worsening COVID-19.

Viral clearance was documented in 78.1% of patients at final viral measurement.

No new safety signals of ensitrelvir were observed in this analysis.