After a prior misfire in demonstrating its protease inhibitor ensitrelvir’s potential as a COVID-19 treatment for U.S. patients, Shionogi has secured an FDA green light for the medicine in the prevention setting.
Sold under the Xocova moniker—and available in Japan since 2022—Shionogi’s oral drug has been cleared for post-exposure prophylaxis (PEP) of COVID-19 in U.S. adults and adolescents ages 12 and older following contact with someone who has COVID.
With the FDA's sign-off, Xocova has earned the distinction of becoming the first oral drug approved in the U.S. to protect against COVID after exposure, Shionogi noted in a June 1 press release. The drug is taken over five days, beginning with three tablets on day one and just one tablet on the following four.
The FDA delivered its green light more than two weeks early, with the agency originally slated to weigh in on Shionogi’s Xocova application by June 16.
Beyond currently approved COVID-19 vaccines from Pfizer-BioNTech, Moderna and Novavax, the U.S. has also cleared antiviral treatments in Pfizer’s Paxlovid, Gilead’s Veklury and Merck & Co.’s Lagevrio, all for treatment after symptom onset.
Shionogi’s drug, meanwhile, “has the potential to benefit anyone who does not want to get COVID-19,” Frederick Hayden, M.D., professor emeritus of clinical virology at the University of Virginia School of Medicine, said in the company’s release.
Aside from use among households, Xocova could offer an appealing prophylactic option in other exposure incidents, including outbreaks in nursing homes and care facilities, and after travel-related contact, Hayden added.
The FDA’s approval hinges on Shionogi’s SCORPIO-PEP trial, in which Xocova curbed the risk of symptomatic COVID-19 by 67% in uninfected people following exposure to someone infected, through 10 days, as weighted against placebo.
Shionogi’s trial enrolled 2,387 participants who had a negative local screening test for the SARS-CoV-2 virus and no symptoms at enrollment after being exposed to an infected person in their household. The company’s primary analysis relied on 2,041 household contact participants with a lab-confirmed negative test at baseline.
The Osaka-headquartered company noted that its antiviral was generally well tolerated, with headache, diarrhea and cough the most common side effects among patients on Xocova.
“Xoxova 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,” Nathan McCutcheon, president and CEO of Shionogi’s U.S. arm, said in a statement. With the drug, “people who are exposed to COVID-19 can act early to help protect themselves,” he added.
While the heyday of COVID-19 vaccine and drug sales has long waned—as evinced by Pfizer and Moderna’s ongoing earnings pressures—Shionogi feels Xocova still has an important niche to fill as the disease remains highly transmissible.
Up to 47% of people who live with someone infected with COVID risk developing it themselves, Shionogi reckons, pointing to CDC estimates that there were some 3.8 million to 12.4 million new COVID cases in the U.S. from the beginning of last October to May 23, 2026. These infections led to hundreds of thousands of outpatient visits, some 240,000 hospitalizations and between 13,000 and 42,000 deaths, according to the data.
In Shionogi’s home country of Japan, Xocova also holds a post-exposure prophylaxis approval. The antiviral was originally greenlit under an emergency nod there as a COVID-19 treatment in November 2022 before securing a full approval in that setting in early 2024.
The medication is also available in Singapore.
With its protection nod, Shionogi has found a new niche in the U.S. market for Xocova, which disappointed in the late-stage SCORPIO-HR trial back in May 2024. In the study, the antiviral failed to chart a statistically significant reduction in time to sustained resolution of 15 common COVID symptoms. That performance caused the study to miss its primary endpoint.
Shionogi leadership admitted at the time that the data were mixed, but they stood behind their asset’s potential and pledged to continue working with regulators to make ensitrelvir more broadly available.
Shionogi clarified in its approval announcement Monday that Xocova is cleared as a preventative and not on offer as a COVID treatment in the U.S.