FDA has approved Shionogi’s Xocova (ensitrelvir) for post-exposure prophylaxis of Covid-19 in adults and adolescents aged 12 years and older following contact with an infected individual.

The approval marks the first and only oral therapy approved in the United States to help prevent Covid-19 after exposure and comes ahead of the drug’s June 16 Prescription Drug User Fee Act action date and expands the role of antiviral therapies beyond treatment into prevention.¹

What was Xocova’s approval based on?

FDA’s decision to approve Xocova was supported by data from the Phase III Scorpio-Pep trial, which Shionogi says is the first oral antiviral study to meet its primary endpoint for preventing symptomatic Covid-19 following exposure.¹ In the study, Xocova reduced the risk of developing symptomatic Covid-19 by 67% through Day 10 compared with placebo among individuals who were not infected at baseline.

“The FDA approval of Xocova provides an important new approach to preventing Covid-19, which continues to impact lives,” said Frederick Hayden, MD, Richardson Professor Emeritus of Clinical Virology and Professor Emeritus of Medicine at the University of Virginia School of Medicine. “Ensitrelvir inhibits viral replication, helping protect people who have been exposed to Covid-19 from developing illness.”

The Scorpio-Pep trial enrolled 2,387 participants aged 12 years and older who tested negative for SARS-CoV-2 and had no symptoms at enrollment but had been exposed to a household member with symptomatic Covid-19.² Participants initiated treatment within 72 hours of symptom onset in the infected household contact.

Safety findings showed similar rates of adverse events between treatment and placebo groups, at 15.1% and 15.5%, respectively.² The most common adverse events reported with Xocova include headache, diarrhea, and cough. No cases of treatment-related dysgeusia, or altered taste sensation, were reported.

“The FDA approval of Xocova is an exciting new chapter in the Shionogi antiviral story,” said Nathan McCutcheon, president and CEO of Shionogi Inc. “Xocova is the first and only oral option clinically proven to help prevent symptomatic Covid-19 after exposure among study participants regardless of vaccination status or baseline immunity from prior infection.”

What is Xocova?

Xocova is a SARS-CoV-2 main protease inhibitor developed through a collaboration between Shionogi and Hokkaido University. The treatment is already approved in Japan for both Covid-19 treatment and prevention, while in the United States the approval is currently limited to post-exposure prophylaxis and does not include treatment of active Covid-19 infection.¹

Xocova is administered as a five-day oral regimen consisting of three tablets on the first day followed by one tablet daily on days two through five.

Why is Xocova’s approval important?

The approval introduces a new prevention strategy at a time when attention is increasingly shifting from pandemic response toward long-term management of endemic SARS-CoV-2 infections. According to data cited by Shionogi, the CDC estimates there were between 3.8 million and 12.4 million Covid-19 cases in the United States between October 2025 and May 2026, resulting in as many as 240,000 hospitalizations and 42,000 deaths.

Sources

1. Shionogi Announces FDA Approval of XOCOVA® (ensitrelvir), the First and Only Oral Option to Help Prevent COVID-19 Following Exposure Shionogi June 1, 2026 https://www.businesswire.com/news/home/20260531335709/en/Shionogi-Announces-FDA-Approval-of-XOCOVA-ensitrelvir-the-First-and-Only-Oral-Option-to-Help-Prevent-COVID-19-Following-Exposure
2. Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts New England Journell of Medicine May 13, 2026 https://www.nejm.org/doi/full/10.1056/NEJMoa2509306