Shionogi's COVID-19 Pill Xocova Faces Phase III Setback, US Filing at Risk

Just two months after receiving full approval in Japan, Shionogi announced on Monday that its oral COVID-19 antiviral, Xocova (ensitrelvir fumaric acid), did not meet the primary goal of time-to-symptom resolution in a global Phase III clinical trial. This outcome could potentially affect Shionogi's plans to file for US regulatory approval next year.

The SCORPIO-HR trial enrolled 2,093 non-hospitalized patients with mild-to-moderate COVID-19 from diverse regions including North America, South America, Europe, Africa, and Asia, during the Omicron-dominant period. Participants were included regardless of their previous infection status. The majority of these participants were vaccinated and were randomly assigned to receive either Xocova or a placebo within three days of symptom onset. The treatment lasted for five days. The primary endpoint of this study was the duration required for sustained symptom resolution, defined as two consecutive days without 15 common COVID-19 symptoms over a 29-day follow-up period.

While Xocova showed a numerical reduction in the time to symptom resolution compared to the placebo, the difference was not statistically significant. However, a pre-specified secondary analysis focusing on six specific symptoms—similar to a previous Phase III study known as SCORPIO-SR involving a narrower group of Asian participants—demonstrated a significant difference in symptom resolution in favor of Xocova over the placebo.

Moreover, the antiviral also significantly reduced viral RNA levels and culture positivity rates compared to the placebo, with no signs of symptomatic viral rebound, aligning with the findings in the SCORPIO-SR trial. No deaths occurred in either group, and COVID-19-related hospitalizations were minimal across both treatment arms. Shionogi plans to present detailed findings at an upcoming conference.

"These top-line 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," commented Simon Portsmouth, head of clinical development at Shionogi. He added that the company would continue to engage with regulatory agencies to determine the future course for the antiviral.

Xocova was granted emergency use authorization in Japan for treating COVID-19 in November 2022 based on the SCORPIO-SR results. Subsequently, Singapore also approved the drug in 2023.

While the global trial results present a nuanced picture, they nonetheless contribute to the growing body of evidence supporting the antiviral efficacy of Xocova. Shionogi's next steps will involve continued discussions with regulatory bodies to navigate the drug's approval process in other regions, including the United States.