Vaccine Info

Xocova (Ensitrelvir) COVID-19 Antiviral

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Last reviewed
April 5, 2023
Fact checked by
Robert Carlson, MD

Xocova® (Ensitrelvir) COVID-19 Antiviral April 2023

Xocova® (ensitrelvir fumaric acid, S-217622) is an oral antiviral for treating people diagnosed with COVID-19. Xocova is a 3CL protease inhibitor created through joint research between Hokkaido University and Shionogi & Co. Lid. Xocova suppresses the replication of the SARS-CoV-2 coronavirus by selectively inhibiting 3CL protease. According to non-clinical trials, Shionogi confirmed high antiviral activity against the Omicron virus variant, similar to other existing variants.

Shionogi presented results on February 21, 2023, from the Phase 3 part of the pivotal SCORPIO-SR trial conducted in Japan, South Korea, and Vietnam at the Conference on Retroviruses and Opportunistic Infections. On April 5, 2023, Shionogi announced late-breaking poster presentations featuring results from the Phase 3 and Phase 2b/3 parts of the pivotal SCORPIO-SR trial (Phase 2/3 study) conducted on ensitrelvir will be published as posters at the 33rd European Congress of Clinical Microbiology & Infectious Diseases in Copenhagen, Denmark 15 - 18 April 2023.

Ensitrelvir is an investigational drug outside of Japan. In addition, the brand name Xocova® has not been approved for use outside of Japan and pertains only to the approved drug in Japan. The U.S. Food and Drug Administration (FDA) granted Fast Track designation on April 4, 2023.

Shionogi & Co., Ltd. is located at 1-8, Doshomachi 3-chome, Chuo-ku, Osaka 541-0045, Japan.

Xocova Indication

Xocova® 125 mg tablet is an oral antiviral agent administered once daily for five days that suppresses the replication of SARS-CoV-2 coronavirus by selectively inhibiting the viral 3CL protease. Morishima Tsuneo, a visiting professor at Aichi Medical University, says the significance of the pill lies in the fact it can be prescribed to people who ostensibly fall into a low-risk category because even these patients could end up developing serious symptoms.

Xocova Availability

A contract with the Japanese government purchasing 1 million courses of Xocova® 125 mg tablet courses became effective in 2022. Approval is pending in South Korea and China in 2023.

Xocova News

April 5, 2023 - “We are encouraged by these new data regarding the potential reduction of transmission among asymptomatic patients and patients with mild COVID-19 symptoms,” said Isao Teshirogi, Ph.D. “We are continuing to evaluate ensitrelvir in multiple patient populations through our robust global clinical program and look forward to continued scientific exchange on this important compound.”

April 4, 2023 - “There is a need for additional COVID-19 treatment options as SARS-CoV-2 continues to affect people in the U.S. Receiving Fast Track designation from the FDA recognizes the potential of ensitrelvir as a once-daily, oral antiviral for SARS-CoV-2,” said Nathan McCutcheon, CEO, Shionogi Inc., the U.S. subsidiary of Shionogi.

March 29, 2023 - Research Article: Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors.

February 21, 2023 - Shionogi & Co., Ltd. presented further results from the Phase 3 part of the pivotal SCORPIO-SR trial (Phase 2/3 study) conducted in Japan, South Korea, and Vietnam of the novel COVID-19 oral antiviral ensitrelvir. Shionogi also presented exploratory data from the Study evaluating the potential effect of ensitrelvir on the symptoms of long COVID. 

February 15, 2023 - The U.S. NIH announced a clinical trial to evaluate Shionogi antiviral in adults hospitalized with COVID-19. Shionogi & Co., Ltd. announced the program includes several Phase 3 clinical studies evaluating ensitrelvir’s safety and effectiveness across a wide range of COVID-19 patient populations.

November 22, 2022 - Shionogi & Co., Ltd. announced that Xocova® obtained emergency regulatory approval from the Ministry of Health, Labour and Welfare in Japan for the indication of SARS-CoV-2 infection. This approval was granted under the emergency regulatory approval system provided for in Article 14-2-2 of the Pharmaceuticals and Medical Devices Act.

March 25, 2022 - Shionogi & Co., Ltd. announced that Shionogi has entered into a basic agreement with the Ministry of Health, Labor and Welfare (MHLW) to supply S-217622 in Japan.

Xocova® Clinical Trials

The Phase 2b/3 part of the Phase 2/3 study targeting SARS-CoV-2 infected persons with asymptomatic/mild symptoms only is being conducted in Asia, mainly in Japan. The first late-breaking poster presentation included a post-hoc analysis of the Phase 3 part showing that viral rebound and symptom recurrence were infrequently seen up to 21 days after treatment with ensitrelvir. Viral RNA rebound by PCR testing was observed in 7.8% in the ensitrelvir 125 mg group (n=590) and 4.7% in the placebo group (n=574). Symptom recurrence was rare and was not associated with viral RNA rebound. Although RNA rebound was observed in a small number of patients, there was only one (1/310) low-level viral titer positive in follow-up, suggesting no concerns for infectivity or transmission.

A second late-breaking poster presentation included new results from the study (Phase 2b/3 part) of patients who tested positive for SARS-CoV-2 but were either asymptomatic or had only mild symptoms at the time of randomization. These results were based on 572 patients who were followed up for ten days after randomization. Ensitrelvir 125 mg showed a significant reduction from baseline viral RNA on Day 4, a reduction of 1.12 log10 copies/mL versus placebo (p<0.0001). The time to the first negative SARS-CoV-2 culture was significantly shorter with ensitrelvir 125 mg compared to placebo (a median time of 38.3 hours versus 66.7 hours, p<0.0001, respectively). Although these results were exploratory, the reduction in viral RNA and faster time to a negative viral culture may be predicted to reduce the period of infectivity, which may have implications for reducing the risk of transmission.

In a subset of 70 asymptomatic patients, ensitrelvir 125 mg (n=23) showed a numerical reduction in the proportion of patients developing symptoms. In the 502 patients presenting with mild symptoms, treated with ensitrelvir 125 mg (n=171), a numerical reduction in the proportion reporting a worsening of symptoms compared with placebo was observed. Ensitrelvir was well tolerated, and no new safety concerns were identified.

A separate Phase 3 study of ensitrelvir (SCORPIO-HR) is underway across Asia, Africa, North America, and Europe in non-hospitalized adults who have tested positive for SARS-CoV-2 and includes those both with and without risk factors for severe disease and regardless of vaccination status. Shionogi also plans to initiate a post-exposure prevention global Phase 3 study, SCORPIO-PEP.

July 26, 2021 - Shionogi initiated a Japanese Phase 1 clinical trial of the therapeutic agent S-217622 as an orally administered antiviral drug for COVID-19, caused by the novel coronavirus (SARS-CoV-2) infection, and the first dose was administered successfully on July 22. No safety concerns have been identified after the first dose.

September 28, 2021 - Shionogi initiated a Japanese Phase 2/3 clinical trial. The Phase 2/3 clinical trial will evaluate the efficacy and safety of oral administration of this drug once daily for five days in patients with mild COVID-19 or asymptomatic SARS-CoV-2 infection compared with a placebo. 

January 31, 2022 - Shionogi presented results up to day 6 of Phase 2a, part of a Phase 2/3 clinical trial of S-217622. The Phase 2b/3 part of a Phase 2/3 clinical trial is underway in mild, moderate, or asymptomatic COVID-19 patients.

Clinical Trials

No clinical trials found