COVID-19 PEP is now approved in U.S. Could it help Canadian healthcare workers or residents of long-term care homes?

The U.S. Food and Drug Administration recently approved ensitrelvir for use as post-exposure prophylaxis (PEP) of COVID-19. The approval comes after results of a large-scale clinical trial suggested a five-day regimen of the oral medication could reduce infection of household contacts of someone with COVID-19.The oral medication could be an important tool for people in long-term care homes or those who have weakened immune systems, experts said.“There’s a role for occupational exposure as well,” said Dr. David Boulware, an infectious-disease specialist at the University of Minnesota Medical School in Minneapolis, when asked to comment for a news piece in Nature in May. PEP could help protect healthcare workers exposed to SARS-CoV-2.The general population may not be the group who will benefit greatly from PEP, given vaccination and increased knowledge of barrier methods to prevent infection, such as masking, hand washing and isolation. Yet there may be some who want to avoid sickness after an unavoidable exposure, Dr. Annie Antar, an infectious-disease specialist at the Johns Hopkins School of Medicine in Baltimore told Nature. “I actually think it would have a wide audience.”The SCORPIO-PEP trial involved 1,030 participants randomized to the ensitrelvir group and 1,011 randomized to the placebo group. The participants all had exposure within 72 hours of randomization to an adult or child in their household who had at least one symptom and tested positive for SARS-CoV-2. The majority (71%) were randomized within 48 hours of symptom onset of the household contact who tested positive for SARS-CoV-2. All the participants tested negative for SARS-CoV-2 at baseline. The intervention group had 375 mg on day one of treatment and then 125 mg on day two to day five of treatment.The participants were mostly healthy, with 37% having risk factors for severe illness, including older age, smoking status and/or obesity. All but 2% tested positive for SARS-CoV2 antibodies. The trial was carried out between June 2023 and September 2024 in Japan, Argentina, South Africa, Vietnam and the U.S.Significantly fewer patients in the ensitrelvir group had COVID-19 at day 10 compared to the placebo group, with an incidence of 2.9% in the ensitrelvir group and 9% in the placebo group. These benefits of ensitrelvir were consistent across subgroups, including older persons and those with risk factors for severe disease. COVID-19 was considered a positive test to SARS-CoV-2 and at least one symptom. Some participants were asymptomatic on day 10 but tested positive for SARS-CoV-2; 14% in the ensitrelvir group and 21.5% in the placebo group. This suggests ensitrelvir also reduces viral transmission.Adverse events were few and were similar in the two groups. The most common adverse events were headache, diarrhea, nasopharyngitis, cough, fatigue or influenza. There were no COVID-19-related hospitalizations or deaths. Ensitrelvir is an inhibitor of a SARS-CoV-2 3C-like protease, the same target as nirmatrelvir, one part of nirmatrelvir-ritonavir marketed as Paxlovid. Findings from a trial examining nirmatrelvir-ritonavir (Plaxovid)’s potential as PEP suggest it did not reduce the risk of COVID-19 after household exposure compared to placebo. The trial was published in the New England Journal of Medicine in 2024. Researchers also studied another anti-viral, molbupiravir, as PEP but it did not show a difference compared to placebo in COVID-19 rates in household contacts. Those trial results published in the Journal of Infection in 2023.Ensitrelvir (XOCOVA) is currently approved in Japan for treating patients 12 years old and older who have COVID-19. It is now approved as COVID-19 post-exposure prophylaxis in Japan and, as of June 1, the U.S.The New England Journal of Medicine published the SCORPIO-PEP trial results in May.

COVID-19 PEP is now approved in U.S. Could it help Canadian healthcare workers or residents of long-term care homes?

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