Shionogi announced its oral COVID-19 drug S-217622 helped patients achieve resolution of five Omicron-related symptoms faster, compared to placebo, thereby meeting the main goal of a phase 3 part of a phase 2/3 study conducted in Asia.
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This study was conducted in patients with mild/moderate symptoms of COVID-19 and assessed clinical symptom resolution with ensitrelvir (2 dose groups; high dose and low dose), orally administered once daily for five days, compared to placebo.
A total of 1,821 patients were enrolled, in Japan, South Korea, and Vietnam, irrespective of risk factors for COVID-19 progression. The majority of patients were previously vaccinated.
The primary endpoint in the study was the time to first resolution of five key COVID-19 symptoms (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness) which are characteristic of infection with the SARS-CoV-2 Omicron variant, in patients randomized within 72 hours from the onset of symptoms.
The five assessed symptoms were selected in consultation with medical experts and regulatory authorities including the Ministry of Health, Labor and Welfare (MHLW), the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan and the U.S. Food and Drug Administration (FDA), based on their scientific and medical validity.
In this population, the median time to first resolution of the five COVID-19 symptoms was significantly reduced in those treated with the low dose of ensitrelvir (the dose level submitted for approval in Japan) compared to placebo: 167.9 hours versus 192.2 hours, a statistically significant difference of 24 hours (p=0.04).
In addition, with respect to the key secondary endpoint of reduction in viral RNA on day 4 (following the third dose), ensitrelvir showed a significant difference versus placebo (p<0.0001) in the Least Squares mean change from baseline in viral RNA; a reduction of more than 1.4 log10 copies/mL versus placebo, similar to the results observed in previous studies1-3.
With regard to safety, both doses of ensitrelvir were well tolerated, and there were no serious adverse events or deaths in this study. In the low-dose group, the most common treatment-related adverse events were decreased high-density lipoprotein and increased blood triglycerides, as observed in previous studies.
The emergency approval of ensitrelvir was deliberated in the Pharmaceutical Affairs and Food Sanitation Council meeting held on July 20, 2022, in Japan, and review will continue based on the results of the Phase 3 part of the study.
The top-line results of the Phase 3 part have been reported to MHLW and PMDA. ■