US FDA Accepts NDA for Ensitrelvir as Post-Exposure COVID-19 Prevention

The US Food and Drug Administration has accepted a New Drug Application for ensitrelvir, an investigational oral antiviral developed by Shionogi & Co., Ltd., for the prevention of COVID-19 following exposure to an infected individual. The agency has set a Prescription Drug User Fee Act action date of June 16, 2026.¹

The application, submitted by Shionogi Inc., is supported by results from SCORPIO-PEP, a global, double-blind, randomized, placebo-controlled phase 3 trial evaluating ensitrelvir as post-exposure prophylaxis. According to the company, SCORPIO-PEP is the first phase 3 study of an oral antiviral to meet its primary end point for preventing COVID-19 following exposure. If approved, ensitrelvir would be the first oral therapy indicated for this purpose.¹

SARS-CoV-2 remains highly transmissible, with up to half of individuals living with an infected household contact developing COVID-19, according to data cited in the release. Despite widespread vaccination, no antiviral therapies are currently approved in the US to prevent COVID-19 after exposure. Vaccines are administered prior to exposure and do not stop viral replication, while currently available antivirals are used after diagnosis, when infection is already established.¹

“Shionogi has a long history of innovation in infectious disease treatment and prevention. Our dedication to this field has led to significant breakthroughs in the development of novel antimicrobials and antivirals for HIV/AIDS, influenza and COVID-19. If approved, ensitrelvir will be the first and only oral therapy to help protect people in the U.S. from COVID-19 following exposure,” said Nathan McCutcheon, MBA, president and chief executive officer of Shionogi Inc., in the company announcement.¹

Ensitrelvir is a SARS-CoV-2 main protease inhibitor developed through joint research between Hokkaido University and Shionogi. By selectively inhibiting the viral main protease, the drug suppresses viral replication, a mechanism intended to prevent development of disease when administered after exposure.¹

The agent is already approved in Japan for the treatment of COVID-19. It initially received emergency regulatory authorization in November 2022, followed by full approval in March 2024, based on findings from the SCORPIO-SR phase 3 trial conducted during the Omicron-dominant period of the pandemic. In that study, ensitrelvir demonstrated clinical symptomatic efficacy—defined as sustained symptom resolution for at least 24 hours for five typical Omicron-related symptoms—as well as antiviral efficacy in a predominantly vaccinated population with mild to moderate COVID-19. Most adverse events were mild, with no deaths reported; commonly observed treatment-related events included transient decreases in high-density lipoprotein cholesterol and increases in blood triglycerides. Results were published in JAMA Network Open.²

Beyond Japan, ensitrelvir has been made available in Singapore through a Special Access Route for COVID-19 treatment and is under regulatory review in Taiwan and by the European Medicines Agency for both post-exposure prophylaxis and treatment. In 2025, Shionogi also submitted applications in Japan for post-exposure prophylaxis and for treatment of pediatric patients aged 6 to younger than 12 years, based on a randomized, double-blind, placebo-controlled trial showing similar pharmacokinetics to adults and confirming safety and tolerability.¹

Ensitrelvir remains an investigational drug outside of Japan and Singapore. The brand name Xocova has not been approved for use outside those countries and refers only to the product approved in those markets.¹

References:

1. FDA Accepts Shionogi’s Ensitrelvir NDA as the First Oral Therapy for the Prevention of COVID-19 Following Exposure. News release. Shionogi. September 2, 2025. Accessed September 2, 2025. https://www.shionogi.com/us/en/news/2025/09/fda-accepts-shionogis-ensitrelvir-nda-as-the-first-oral-therapy-for-the-prevention-of-covid-19-following-exposure.html
2. Jennings S. Investigational Oral Antiviral Ensitrelvir Reduces Time to Resolution of Common COVID-19 Symptoms. Patient Care Online. April 10, 2023. https://www.patientcareonline.com/view/investigational-oral-antiviral-ensitrelvir-reduces-time-to-resolution-of-common-covid-19-symptoms