An exploratory phase 2b/3 randomized, placebo-controlled trial has indicated that ensitrelvir may offer a potential reduction in the risk of developing or worsening COVID-19 symptoms. The multi-center trial, conducted across 57 medical institutions in Japan, South Korea, and Vietnam between January and August 2022, investigated the efficacy and safety of ensitrelvir in individuals with asymptomatic SARS-CoV-2 infection and patients experiencing mild COVID-19 symptoms.
The study, the results of which were recently published, randomized 572 participants to receive either ensitrelvir at 125-mg or 250-mg doses, or a placebo. Participants self-reported the severity of 14 typical COVID-19 symptoms in an electronic diary. The primary endpoint focused on the impact of ensitrelvir on the development and progression of these symptoms.
Efficacy and Safety Outcomes
The results showed that the ensitrelvir 125-mg group experienced a 77% reduction in the risk of developing any of the 14 COVID-19 symptoms or fever compared to the placebo group. Additionally, there was a 29% reduction in the risk of worsening of such symptoms or fever, although this result did not reach statistical significance. Notably, the study observed a statistically significant decrease in viral RNA, viral titer, and time to infectious viral clearance in the ensitrelvir groups compared to placebo, demonstrating antiviral efficacy.
Regarding safety, most treatment-related adverse events (TEAEs) were mild to moderate in severity. The most common TEAE observed across all groups was a decrease in high-density lipoprotein.
Implications and Future Directions
These exploratory findings suggest that ensitrelvir could be a valuable therapeutic option for managing COVID-19, particularly in reducing the risk of symptom development and viral load. Further research is warranted to confirm these findings and to explore the optimal dosing regimen and patient populations that would benefit most from ensitrelvir treatment. The trial's registration number is jRCT2031210350.
