Updates from SCORPIO-HR, a global phase III study of ensitrelvir for non-hospitalized participants with COVID-19 – Shionogi

Shionogi & Co., Ltd. announced that its pivotal, double-blind, randomized, placebo-controlled global Phase III study (SCORPIO-HR) did not meet its primary endpoint of a statistically significant reduction in time to sustained resolution (symptoms completely absent for at least two days) of 15 common COVID-19 related symptoms for once-daily ensitrelvir (Generic name: ensitrelvir fumaric acid, Code No.: S-217622, hereafter “ensitrelvir”), when treatment was initiated within three days of symptom onset, compared to placebo.

A pre-defined supportive analysis of resolution (symptoms completely absent for at least one day) of six symptoms using a statistical method similar to that used in the SCORPIO-SR Study (Phase III part of the Phase II/III study of ensitrelvir conducted in Asia) yielded a significant difference (p<0.05) in the time to resolution of symptoms. Ensitrelvir demonstrated a potent antiviral effect, leading to a substantial reduction from baseline in viral RNA levels and viral culture positivity compared to placebo. Symptomatic viral rebound did not occur in this study, which is consistent with previous findings from SCORPIO-SR.

The SCORPIO-HR study was carried out across a broad range of symptomatic, non-hospitalized participants with COVID-19, regardless of past SARS-CoV-2 infection. This study enrolled participants in North America, South America, Europe, Africa and Asia and was conducted when Omicron variant infection was predominant. Most participants were vaccinated, and approximately 30% had risk factors for severe disease, including obesity (BMI?30 kg/m2), hypertension and diabetes mellitus. The SCORPIO-HR trial is a part of the National Institutes of Health’s (NIH) Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership, and it is being conducted as a collaboration between Shionogi, the National Institute of Allergy and Infectious Diseases (NIAID), a part of the NIH, and ACTG, a global clinical trials network focused on HIV and other infectious diseases and funded by NIAID.

Ensitrelvir was granted Fast Track designation by the FDA in 2023. The Fast Track program facilitates the expedited development and review of new drugs that are intended to treat serious or life-threatening conditions and to demonstrate the potential to address unmet medical needs. In Japan, ensitrelvir, known as Xocova, received emergency regulatory approval in 2022 and full approval in March 2024. Since its emergency approval, more than one million people have been treated with ensitrelvir in Japan. Ensitrelvir was also approved in Singapore based on the Special Access Route application in 2023. It remains an investigational drug outside of Japan and Singapore.