Shionogi & Co., Ltd. announced positive results from its global Phase 3 SCORPIO-PEP trial, revealing that once-daily ensitrelvir significantly reduced the proportion of participants developing symptomatic SARS-CoV-2 infection following exposure to household contacts with COVID-19. The double-blind, randomized, placebo-controlled study met its primary endpoint, demonstrating the potential of ensitrelvir as a post-exposure prophylactic (PEP) treatment.
The SCORPIO-PEP trial (Stopping COVID-19 pRogression with early Protease InhibitOr treatment – Post Exposure Prophylaxis) included approximately 2,400 participants aged 12 years and older from the U.S., South America, Africa, and Asia. Participants, who had a negative SARS-CoV-2 screening test and no symptoms but were exposed to a symptomatic household member with COVID-19, were randomized 1:1 to receive either 125 mg of ensitrelvir or a placebo once daily for five days. Treatment commenced within three days of the household member exhibiting symptoms.
The primary endpoint assessed the onset of COVID-19 symptoms through Day 10. Ensitrelvir was well-tolerated, and no new safety concerns were observed during the study.
Mechanism of Action and Regulatory Status
Ensitrelvir, an investigational oral antiviral, functions by selectively inhibiting the viral 3CL protease, thereby suppressing SARS-CoV-2 replication. The drug received Fast Track designation from the U.S. Food and Drug Administration in 2023 for COVID-19 treatment. In Japan, it is approved as Xocova® for COVID-19 treatment under emergency regulatory approval in 2022 and full approval in March 2024. It is also available in Singapore via the Special Access Route since 2023. Outside of Japan and Singapore, ensitrelvir remains an investigational drug.
Clinical Significance
"COVID-19 remains an important public health priority, yet there are currently no oral antiviral medications approved for post-exposure prophylactic use. There is a need for convenient, preventive approaches to protect ourselves and those close to us from contracting SARS-CoV-2," said Simon Portsmouth, MD, FRCP, Senior Vice President, Head of Clinical Development at Shionogi. "These data demonstrate a new potential for post exposure prophylactic use of ensitrelvir, expanding on the breadth of clinical and real-world evidence that establish its activity in those infected with SARS-CoV-2."
Further Details
Additional information about the SCORPIO-PEP study can be found on clinicaltrials.gov (NCT05897541). Shionogi plans to submit detailed results from the SCORPIO-PEP trial for presentation at a future scientific conference.
