In the phase 2b portion of a phase 2/3 clinical study, 5 days of the once-daily, novel, oral SARS-CoV-2 3C-like protease inhibitor ensitrelvir fumaric acid (S-217622) had a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile in patients with mild-to-moderate COVID-10, researchers report. The study results, obtained during the omicron portion of the COVID-19 pandemic, are similar to findings during phase 2a, when the delta variant was dominant.
Participants were randomized to ensitrelvir fumaric acid 125 mg (375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. Based on co-primary endpoints of the change from baseline in SARS-CoV-2 titer on day 4 and time-weighted average change from baseline up to 120 hours in the total score of 12 predefined COVID-19 symptoms, the investigators found: “A total of 341 patients (ensitrelvir 125-mg group: 114; ensitrelvir 250-mg group: 116; and placebo group: 111; male: 53.5–64.9%; mean age: 35.3–37.3 years) were included in the efficacy analyses. The change from baseline in SARS-CoV-2 titer on day 4 was significantly greater with both ensitrelvir doses than with placebo (differences from placebo: −0.41 log10 50% tissue-culture infectious dose/mL; P < .0001 for both). The total score of the 12 COVID-19 symptoms did not show a significant difference between the ensitrelvir groups and placebo group. The time-weighted average change from baseline up to 120 hours was significantly greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse events were mild in severity.”