Shionogi Announces Xocova® (Ensitrelvir Fumaric Acid) Obtained Standard Approval in Japan for the Treatment of SARS-CoV-2 Infection

OSAKA, Japan, March 5, 2024 – Shionogi & Co., Ltd. (Head Office: Osaka, Japan; Chief Executive Officer: Isao Teshirogi, Ph.D.; hereafter “Shionogi”) announced that it has obtained standard approval from the Ministry of Health, Labour and Welfare (MHLW) for Xocova® (Generic name: ensitrelvir fumaric acid), a novel anti-SARS-CoV-2 drug for the indication of SARS-CoV-2 infection in Japan. Shionogi obtained emergency regulatory approval for Xocova® in November 2022 and submitted an application for standard approval in May 2023. Xocova® is the first COVID-19 treatment antiviral to receive standard approval in Japan.

The standard approval of Xocova® is based on positive results from the Phase 3 portion of Phase 2/3 study (SCORPIO-SR) conducted in Japan, South Korea and Vietnam¹. The study was conducted in a predominantly vaccinated population, regardless of risk factors for severe disease. Xocova® is the first antiviral agent to show both clinical symptomatic efficacy for five typical COVID-19 symptoms (primary endpoint) and antiviral efficacy in patients with mild-to-moderate SARS-CoV-2 infection*.

Furthermore, we have included additional results regarding the efficacy, such as viral titers, as well as safety information from over 900,000 patients (estimated) obtained in post-emergency approval use in support of the standard approval application.

As a result, the regulatory authorities determined that the efficacy and safety of Xocova® has been sufficiently confirmed to grant standard approval. With this standard approval, it is no longer necessary to obtain written consent from the patient before the prescription of Xocova® and it is expected that Xocova® can be used with greater confidence and contribute even further to the treatment of a broad range of COVID-19 patients, regardless of risk factors for severe disease.

Ensitrelvir (known in Japan as Xocova®), an oral antiviral drug for COVID-19 currently approved under the emergency regulatory approval system in Japan, is a 3CL protease inhibitor created through joint research between Hokkaido University and Shionogi. SARS-CoV-2 has an enzyme called 3CL protease, which is essential for the replication of the virus. Ensitrelvir suppresses the replication of SARS-CoV-2 by selectively inhibiting the 3CL protease. Ensitrelvir is the first antiviral agent to show both clinical symptomatic efficacy for five typical Omicron-related symptoms (primary endpoint) and antiviral efficacy (key secondary endpoint) in a predominantly vaccinated population of patients with mild-to-moderate SARS-CoV-2 infection, regardless of risk factors, in the results of the Phase 3 part of the Phase 2/3 study conducted during the Omicron-dominant phase of the epidemic. With regard to safety, most adverse events were mild in severity and no deaths were seen in the study. Among the most common treatment-related adverse events were temporary decreases in high-density lipoprotein and increased blood triglycerides, as observed in previous studies. Initial exploratory analyses from the Phase 2/3 study also indicated a potential for reduced risk of development of long COVID and further evaluations in this regard are still ongoing.

The U.S. Food and Drug Administration (FDA) granted Fast Track designation to ensitrelvir for COVID-19. FDA Fast Track designation is designed to facilitate the development and expedite the review of potential new therapies that treat serious conditions and fulfill an unmet medical need. Ensitrelvir was approved in Singapore in November 2023 based on the Special Access Route application. Ensitrelvir remains an investigational drug outside of Japan and Singapore. In addition, the brand name Xocova® has not been approved for use outside of Japan and Singapore and pertains only to the approved drug in Japan and Singapore.

As SARS-CoV-2 continuously evolves, Shionogi is studying its investigational oral antiviral, ensitrelvir, across a range of patient populations and disease severity to evaluate how ensitrelvir may address the current needs. Shionogi has a comprehensive, global clinical development program underway for ensitrelvir that includes four Phase 3 trials, including SCORPIO-HR, a trial for non-hospitalized, symptomatic COVID-19 patients who have tested positive for COVID-19. SCORPIO-HR is also evaluating the potential effect of ensitrelvir on the symptoms of long COVID. An investigator-initiated research study is also ongoing in hospitalized patients for the management of COVID-19 as part of the new Strategies and Treatments for Respiratory Infections & Viral Emergencies (STRIVE) platform protocol. SCORPIO-PEP is evaluating the safety and efficacy in the prevention of symptomatic SARS-CoV-2 infection when exposed to household contacts who are symptomatic and tested positive for SARS-CoV-2. Lastly, Shionogi is studying the safety and efficacy of ensitrelvir in Japan for children between the ages of 6 to 11 years old.

Shionogi is committed to “Protect people worldwide from the threat of infectious diseases” with research and development of therapeutics, whilst also working towards total care through awareness building, epidemiologic monitoring, prevention, diagnosis, and addressing exacerbations, as well as treating infections directly. As SARS-CoV-2 continues to have a major impact on people’s lives and to represent a global threat, Shionogi will seek to contribute to re-establishing the safety and security of society by developing new products and services to address this pandemic. Shionogi is committed to equitable access worldwide, including by working with the Medicines Patent Pool to provide access to low- and middle-income countries (LMICs), and by strengthening its manufacturing and global supply chain.

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1. Xocova® (Ensitrelvir Fumaric Acid) Tablets 125mg Approved in Japan for the Treatment of SARS-CoV-2 Infection, under the Emergency Regulatory Approval System Available at: Xocova® (Ensitrelvir Fumaric Acid) Tablets 125mg Approved in Japan for the Treatment of SARS-CoV-2 Infection, under the Emergency Regulatory Approval System｜News｜Shionogi Co., Ltd.

* Literature search conducted in January 2024