Background:
Ensitrelvir is a SARS-CoV-2 3CL protease inhibitor approved in Japan under emergency regulatory approval system as an oral treatment for COVID-19. Here we report the key analysis results of 125 mg group of phase3 part (SCORPIO-SR).
Methods:
This study was a multicenter, randomized, double-blind, placebo-controlled study. Regardless of SARS-CoV-2 vaccination status and presence of risk factors for severe disease, patients with mild-to-moderate COVID-19 within 120 hours from onset were randomized to oral administration of ensitrelvir 125 mg (375 mg loading dose on Day1), ensitrelvir 250 mg (750 mg loading dose on Day1), and placebo once daily, for 5 days. The primary endpoint was time to resolution of 5 symptoms of COVID-19 (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness), and the key secondary endpoints include change from baseline on Day4 in the amount of SARS-CoV-2 viral RNA and time to first negative of viral titer. The primary population for the primary and key secondary endpoints was patients with < 72 hours from onset to randomization.
Results:
Median time to resolution of 5 symptoms was significantly shorter in 125 mg group (n=336, 167.9 hours) than placebo group (n=321, 192.2 hours) (p=0.0407). Mean change of viral RNA levels from baseline (log10 copies/mL) on Day4 was significantly greater in 125 mg group (-2.48) than in placebo group (-1.01) (p < 0.0001). The time to first negative of viral titer was significantly shorter in 125 mg group (n=199, 36.2 hours) compared to placebo group (n=211, 65.3 hours) (p < 0.0001). Mean changes from baseline in viral titers [log10(TCID50)/mL] were significantly greater in 125mg group on Day2 (-0.807, n=196) and Day4 (-1.108, n=197) than in the placebo group (-0.395, n=208 and -0.850, n=207, respectively) (p < 0.0001). Ensitrelvir Placebo 125mg250mgN336329321Median Time (hours) to Resolution of 5 COVID-19 Symptoms 167.9171.2192.2Difference vs placebo-24.3-21.0-p-value0.04070.0203-In the patients randomized within 120 hours of onset, median time to resolution of 5 symptoms was 189.7 hours in 125 mg group (n=582) and 200.3 hours in placebo group (n=572) (p=0.4352). No deaths or serious adverse drug reactions were reported in either group, and the incidence of serious adverse events between the two groups was comparable.
Conclusions:
Ensitrelvir demonstrated a significant reduction in the time to resolution of 5 typical symptoms of COVID-19, robust antiviral effects and good tolerability.
