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The US FDA has approved oral ensitrelvir for postexposure protection against COVID for adults and adolescents aged 12 years or older, according to a press release from manufacturer Shionogi.
Ensitrelvir, marketed as Xocova, works by inhibiting viral replication and is designed as a 5-day oral protective regimen, with three tablets taken on day 1 after exposure and one additional tablet taken on days 2-5. The approval occurred ahead of the Prescription Drug User Fee Act action date of June 16, 2026, according to the company.
“COVID-19 still causes a substantial burden of disease, yet there is very little that can be done following exposure to an infected individual, so that a clear unmet need exists for an easily administered oral therapy for those who have been exposed to COVID-19,” said Frederick Hayden, MD, professor emeritus of clinical virology and professor emeritus of medicine, University of Virginia School of Medicine, Charlottesville, Virginia, and lead author of the SCORPIO-PEP study on which the approval was based.
Data from the SCORPIO-PEP trial were published in The New England Journal of Medicine in May and presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025 Annual Meeting.
The modified intent-to-treat study population included 1030 individuals who tested negative for COVID at baseline and were randomly assigned to ensitrelvir and 1011 individuals who were randomly assigned to placebo. The mean age of the participants was 42.4 years, and 71.1% underwent randomization within 48 hours of symptom onset in the exposed person.
Treatment with ensitrelvir reduced the risk for symptomatic COVID by 67% compared with placebo treatment in uninfected individuals up to 10 days after exposure to an infected individual. Adverse events were similar between the groups (approximately 15% for adverse events overall), and the most common included headache, diarrhea, and cough.
The SCORPIO-PEP data reflect results from seasonal influenza trials in which timely antiviral postexposure prophylaxis was highly effective in protecting household contacts from developing illness, Hayden said. A key distinction in the SCORPIO-PEP study was the early initiation of ensitrelvir prophylaxis within 72 hours of exposure, as approximately 70% of participants started PEP within 48 hours, he noted.
“What stood out to me was the overall consistency of the efficacy data in a real-world household exposure setting, where transmission risk is known to be high,” he added.
Ensitrelvir can offer an important new option for protecting against COVID in exposed persons, particularly in those at higher risk for complications, Hayden said. The regimen could be useful in household settings and other exposure circumstances, such as outbreaks in nursing homes and chronic or acute care facilities, and following travel-related exposures, he added.
“The SCORPIO-PEP study generated strong and encouraging data, which served as the basis for its new drug application submission to the FDA,” Hayden said. “The focus now is on understanding how these findings fit within the broader COVID-19 management landscape,” he said. “Additional data can help further characterize the consistency of PEP effectiveness and implementation strategies across populations, clinical circumstances like facility outbreaks, and real-world use,” he said.
The SCORPIO-PEP study was supported by Shionogi.
