Shionogi Enrolls the First Participant in Japan in its Global Phase 3 Trial of Ensitrelvir for the Prevention of Symptomatic SARS-CoV-2 Infection
12 June 2023 - - The first participant has been enrolled in Japan in Japan-based Shionogi & Co., Ltd's global Phase 3 study, Stopping COVID-19 pRogression with early Protease InhibitOr treatment Post Exposure Prophylaxis (SCORPIO-PEP), the company said.

The study will evaluate the safety and efficacy of the novel COVID-19 oral antiviral ensitrelvir (Generic name: ensitrelvir fumaric acid, Code No.: S-217622, hereafter "ensitrelvir") for the prevention of symptomatic SARS-CoV-2 infection in study participants exposed to household contacts who are symptomatic and tested positive for SARS-CoV-2, when compared to placebo. The first participant is expected to be enrolled in the US in July.

In addition, Shionogi also announced that it has filed for full approval of ensitrelvir in Japan.

Ensitrelvir is an investigational oral antiviral that suppresses the replication of SARS-CoV-2 by selectively inhibiting the viral 3CL protease.

Known as Xocova in Japan, ensitrelvir received emergency regulatory approval from the Ministry of Health, Labour and Welfare for the treatment of SARS-CoV-2 infection in November 2022. It remains an investigational drug outside Japan.

In April 2023, ensitrelvir was granted Fast Track designation by the US Food and Drug Administration.

COVID-19 is a significant public health priority. It is expected to remain a continually transmitted respiratory disease that individuals and public health systems will need to manage.

It is also anticipated that new variants of SARS-CoV-2 will emerge, but it is not known how these variants could affect viral transmission, severity of COVID-19, or effectiveness of current therapies.

This randomized, double-blind, placebo-controlled global study will recruit approximately 2,200 participants across North America, South America, Europe, Africa and Asia. Study participants who have a negative screening test for SARS-CoV-2 infection and have had exposure to a household person with symptomatic COVID-19 will be randomly assigned in a 1: 1 ratio to receive ensitrelvir or placebo.

The primary endpoint for the study is the proportion of participants who are infected with SARS-CoV-2 and have COVID-19 symptoms onset through Day 10.

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 reduced risk of development of long COVID and further evaluations in this regard are still ongoing.

Recently, the US Food and Drug Administration 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 remains 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.

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.

Additionally, Shionogi conducted SCORPIO-SR in patients with mild-to-moderate COVID-19 irrespective of risk factors for COVID-19 progression.