Shionogi’s ensitrelvir fumaric acid (ensitrelvir) – an investigational protease inhibitor being evaluated as an antiviral treatment for COVID-19 – demonstrated a significant reduction in symptoms compared with a placebo in the phase 3 part of the phase 2/3 study in Asia, the company announced.
The study was conducted in patients with mild to moderate symptoms of COVID-19 and assessed clinical symptom resolution with two dose groups of ensitrelvir, orally administered once daily for five days, compared to placebo.
A total of 1,821 predominantly vaccinated patients were enrolled in Japan, South Korea and Vietnam, irrespective of risk factors for COVID-19 progression.
The study met its primary endpoint of reduction in the time taken to resolve five key COVID-19 symptoms – stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness – that are characteristic of an Omicron-variant infection.
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 US Food and Drug Administration (FDA), based on their scientific and medical validity.
In patients randomised within 72 hours from the onset of symptoms, ensitrelvir demonstrated a ‘statistically significant’ difference in the median time to first resolution of the five COVID-19 symptoms – the dose level submitted for approval in Japan – compared to placebo.
Both doses of ensitrelvir were well tolerated, and there were no serious adverse events or deaths in the study, the company reported.
The emergency approval of ensitrelvir was deliberated in the Pharmaceutical Affairs and Food Sanitation Council meeting held in July 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.
‘We will continue to consult closely with both organisations for review and deliberation on approval of ensitrelvir while we continue analysis of data and the preparation of additional filing documents,’ Shionogi noted in a statement.
The phase 2b/3 part of a trial in Asian patients – mainly in Japan – with asymptomatic/mild symptoms is still in progress and the global phase 3 trial for SARS-CoV-2 infected patients is also underway.