Shionogi’s once-daily Covid-19 antiviral ensitrelvir missed the primary endpoint in a Phase 3 study, two months after scoring full approval in Japan.
In the NIH-partnered SCORPIO-HR study, ensitrelvir didn’t show a statistically significant reduction in “time to sustained resolution,” or patients being completely clear of 15 different symptoms for at least two days when the drug was given within three days of symptoms starting, compared to placebo.
The antiviral was developed in a joint research collaboration between Hokkaido University and Shionogi — it targets an enzyme in the SARS-CoV-2 virus called 3CL protease, which is essential for the replication of the virus.
However, Shionogi did note that in a separate analysis where patients showed no sign of six different symptoms for at least one day, there was a “significant difference” earning a p-value of 0.05 compared to placebo. Ensitrelvir also showed a “potent antiviral effect, leading to a substantial reduction from baseline in viral RNA levels and viral culture positivity compared to placebo,” and there were no symptomatic viral rebounds in patients in the trial, according to the company.
The global trial included mostly-vaccinated, symptomatic, non-hospitalized participants with Covid-19, and was conducted when the Omicron variant was predominant. About 30% of trial participants had risk factors for severe disease, like obesity and diabetes.
Simon Portsmouth, Shionogi’s senior VP and head of clinical development, said in a statement that the company would continue working with regulatory agencies to make ensitrelvir available. More detailed data will be presented at an upcoming medical meeting.
Simon Portsmouth“These topline results, while mixed, confirm an antiviral effect and add to the existing clinical data and real-world evidence that we have seen for ensitrelvir in Asia,” Portsmouth added. “No new safety concerns were identified. Ensitrelvir had similar tolerability to placebo and there were no reports of taste disturbance.”
Ensitrelvir, which was granted fast track designation by the FDA in 2023, also snagged full approval in Japan in March after receiving emergency regulatory approval in 2022. Marketed as Xocova, it was the first drug approved under Japan’s emergency regulatory approval system. The emergency approval was based on data that showed when patients took the drug for five days, it led to a significant reduction in symptoms within 72 hours of its onset.