Japanese pharmaceutical company, Shionogi, recently announced results from their ongoing phase 3 study that showed their antiviral, ensitrelvir, was able to shorten the 5 most common COVID-19 symptoms including, runny/stuffy nose, sore throat, cough, feeling hot or feverish, and low energy/tiredness, by approximately 1 day vs placebo.¹

This data comes from the phase 3 study portion of its double-blind, randomized, placebo-controlled SCORPIO-SR trial in patients who are characterized as having mild to moderate COVID-19 in Japan, South Korea, and Vietnam. According to Shionogi, this makes ensitrelvir the first antiviral agent to show both clinical symptom improvement and antiviral effect in a predominantly vaccinated population with Omicron infection regardless of risk factors.²

The results were published in JAMA Network Open.

“We’re pleased to present the data from our phase 3 study conducted in Asia in this peer-reviewed article. These results demonstrate accelerated resolution in a range of symptoms, reinforcing the potential of ensitrelvir across multiple patient profiles. Additionally, ensitrelvir reduced viral RNA levels and time to first negative viral titer, suggesting it could help reduce transmission of SARS-CoV-2,” Takeki Uehara, PhD, senior vice president, Drug Development and Regulatory Science at Shionogi, said in a statement. “This study was conducted in a largely vaccinated population that included patients infected with Omicron. The patients also had varying risk factors for severe disease. This is relevant as there is a lack of data and a need for additional treatment options for this population.”²

Study Results

For the primary analysis, the median time to symptom resolution was approximately 7 days (ensitrelvir group) vs 8 days (placebo) Participants were administered a once-daily ensitrelvir, 125mg, and those included in the primary analysis were randomized less than 72 hours from symptom onset.1More than 90% of patients had received 2 or more doses of the COVID-19 vaccine and patients were included regardless of risk factors for severe disease.¹

The study also met its 2 key secondary endpoints (primary analysis population), as previously presented at the Conference on Retroviruses and Opportunistic Infections 2023. The amount of viral RNA was significantly lower on day 4 in the 125 mg ensitrelvir group compared with placebo (least squares mean change from baseline -2.48 log10 copies/mL versus -1.01 log10 copies/mL, p<0.001).¹ 

The time to achieve first negative infectious viral titer in nasal swabs, indicating clearance of infectious virus from the upper airways, was significantly shorter in the ensitrelvir 125 mg group compared with placebo (a median time of 36.2 hours versus 65.3 hours, p<0.001).1 This is the first study of an oral antiviral for COVID-19 in humans to show a statistically significant reduction in the time to negative infectious viral titer versus placebo.¹

The Agent

Ensitrelvir is a selective SARS-CoV-2 3CL protease inhibitor, and received emergency regulatory approval from the Ministry of Health, Labour and Welfare in Japan for COVID-19 treatment in November 2022. Outside of Japan and Singapore, ensitrelvir is an investigational therapy. In the United States, the FDA granted the antiviral fast track status.³

In a previous interview with Contagion, Yohei Doi, MD, professor of Medicine and director of the Center for Innovative Antimicrobial Therapy at the University of Pittsburgh and professor of Microbiology and Infectious Diseases at Fujita Health University and one of the investigators in this study provided insights on ensitrelvir, its mechanism of action, and one of the studies within the SCORPIO-SR trial.

References

1.Yotsuyanagi H, Ohmagari N, Doi Y, et al. Efficacy and Safety of 5-Day Oral Ensitrelvir for Patients With Mild to Moderate COVID-19: The SCORPIO-SR Randomized Clinical Trial. JAMA Netw Open. 2024;7(2):e2354991. doi:10.1001/jamanetworkopen.2023.54991
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814871

2.Shionogi Announces New Phase 3 Data Showing Early Resolution of Many Common COVID-19 Symptoms in JAMA Network Open. Shionogi press release. February 9, 2024. Accessed February 26, 2024. https://www.shionogi.com/global/en/news/2024/02/E_20240213_1.html

3.Parkinson J. Can an Antiviral Reduce the Taste and Smell Disorder Associated With COVID-19? ContagionLive. November 17, 2023. https://www.contagionlive.com/view/can-an-antiviral-reduce-the-taste-and-smell-disorder-associated-with-covid-19-