The U.S. Food and Drug Administration (FDA) has officially approved an oral anti-COVID-19 drug called Ensitrelvir for post-exposure prophylaxis (PEP). This is the first and currently only oral drug approved for post-exposure prophylaxis against COVID-19 in the United States. It will be marketed in the United States under the trade name "Xocova". The drug was developed by the Japanese pharmaceutical company Shionogi and has been approved for use in Japan as early as 2024.
Ensistevir is an antiviral drug against SARS-CoV-2. Its mechanism of action is to inhibit viral replication, thereby reducing the risk of infection and disease after exposure to the virus. The drug is a 5-day oral regimen: the loading dose is 3 tablets on the first day, and then 1 tablet daily for several consecutive days. The researchers pointed out that this PEP strategy can be used for close household contacts, and can also be extended to outbreak scenarios in nursing homes, chronic or acute medical institutions, and travel-related exposures. It is suitable for the general population who "do not want to be infected with the new crown".
In the pivotal SCORPIO‑PREP Phase III clinical trial, a total of 1,030 subjects who had household contact with a symptomatic COVID-19 case within 72 hours of exposure received ensistevir, and 1,011 subjects received placebo. The results showed that compared with the control group, Xocova reduced the risk of symptomatic COVID-19 by 67% from day 10 after exposure, showing a significant post-exposure preventive and protective effect.
In terms of safety, the incidence of adverse reactions in the ensistevir and placebo groups was similar, with the most common ones being headache, diarrhea and cough. The incidence of adverse events was 15.1% in the ensistevir group and 15.5% in the placebo group; serious adverse events were extremely rare, only 0.2% in both groups. In this study, none of the COVID-19 infections progressed to the point of requiring hospitalization.
Frederick Hayden, a professor at the University of Virginia School of Medicine who participated in the study, said in a statement released by Shionogi that the approval of Xocova provides an important new way to prevent the new coronavirus that continues to affect people’s lives. He emphasized that COVID-19 can not only cause severe acute illness, but even if the condition is mild to moderate, it may aggravate existing chronic underlying diseases or induce new health problems including "COVID-19 growth". He believes that by inhibiting viral replication, ensistevir can help protect exposed people from getting sick, and its PEP strategy has the potential to benefit a wider population.
Nathan McCutcheon, President and CEO of Shionogi USA, pointed out that Xocova is the first and currently only oral drug clinically proven to help prevent symptomatic COVID-19 after exposure, and its protective effect is not affected by previous vaccination status or basic immunity formed by previous infections. He said this means that people can proactively take measures to protect themselves earlier after being exposed to COVID-19.
Previously, antiviral drugs such as molnupiravir (trade name Lagevrio) were mainly used to reduce the severity of disease in infected patients rather than for post-exposure prophylaxis. The launch of ensistevir (Xocova) extends the drug intervention against COVID-19 from "treating infected persons" to "blocking the occurrence of infection", filling the gap in oral post-exposure prophylaxis drugs in terms of prevention and control strategies.
According to the currently approved indications, Xocova is suitable for all adults and adolescents aged 12 years and above. The complete results of the relevant Phase III study have been published in the New England Journal of Medicine (NEJM), providing key evidence-based basis for regulatory approval.