Ensitrelvir reduces household spread of SARS-CoV-2, study shows

ByStephen I. Feller

Fact checked byKristen Dowd

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Key takeaways:

Ensitrelvir was effective as post-exposure prophylaxis against COVID-19 if taken within 72 hours of exposure to SARS-CoV-2.
The drug was granted fast-track designation by the FDA earlier this year.

SAN FRANCISCO — Ensitrelvir reduced transmission of SARS-CoV-2 by 67% when given to uninfected household contacts of a person with COVID-19 within 3 days of that person developing symptoms, researchers reported.

“Oral ensitrelvir post-exposure prophylaxis within 72 hours after symptom onset in index patients was effective in significantly protecting household contacts from COVID-19, including those at high risk,” Frederick G. Hayden, MD, professor of medicine and pathology in the University of Virginia School of Medicine, said during a presentation at the Conference on Retroviruses and Opportunistic Infections.

IDN0325Hayden_Graphic_01_WEB — Data derived from Fukushi A, et al. Abstract 200. Presented at: Conference on Retroviruses and Opportunistic Infections; March 9-12, 2025; San Francisco.

Ensitrelvir has been approved to treat COVID-19 in Japan since last year, is available in Singapore and is being considered for approval in Taiwan, according to Shionogi, its manufacturer.

In the United States, the FDA granted ensitrelvir fast-track designation as a COVID-19 therapeutic in 2023 and an additional fast-track designation earlier this year for use as post-exposure prophylaxis, according to Shionogi.

As part of the SCORPIO-PEP double-blind, placebo-controlled trial, Hayden and colleagues enrolled 2,389 household contacts of index patients with COVID-19 who had tested negative for SARS-CoV-2 between June 2023 and August 2024. The researchers split these participants into two groups: one with confirmatory negative COVID-19 RT-PCR laboratory tests and one without laboratory tests. The groups had the same primary endpoint: proportion of household contacts who developed COVID-19 by day 10 after the start of an index case’s symptoms.

Among 2,041 participants with negative COVID-19 RT-PCR laboratory tests, the researchers randomly assigned them in a 1:1 ratio to receive either ensitrelvir (n = 1,030) or a placebo (n = 1,011) within 72 hours of symptom onset in their COVID-19-positive housemates, according to Hayden. Among this group, the mean age of participants was 42.4 years and 37% had at least one high-risk factor for severe SARS-CoV-2 infection.

The researchers reported that the proportion of people in the ensitrelvir group who developed COVID-19 was significantly lower than in the placebo group (2.9% vs. 9%; RR = 0.33; 95% CI, 0.22-0.49).

In the overall group — 1,194 received ensitrelvir and 1,193 received a placebo — the researchers reported similar efficacy data for an observed risk ratio for developing COVID-19 of 0.43 (95% CI, 0.32-0.59).

Additionally, treatment-emergent adverse events were similar between the treatment and placebo groups, Hayden said.

“The ensitrelvir post-exposure prophylactic reductions in COVID-19 events within households suggest a potential for protection in other settings where there is virus transmission, such as outbreaks in acute- or long-term care facilities,” Hayden said.

References:

Fukushi A, et al. Abstract 200. Presented at: Conference on Retroviruses and Opportunistic Infections; March 9-12, 2025; San Francisco.
Late-breaking at CROI 2025: SCORPIO-PEP phase 3 trial — ensitrelvir is the first and only COVID-19 oral antiviral to demonstrate prevention of COVID-19 as post exposure prophylaxis. https://www.shionogi.com/us/en/news/2025/03/late-breaking-at-croi-2025-scorpio-pep-phase-3-trial-ensitrelvir-is-the-first-and-only-covid-19-oral-antiviral-to-demonstrate-prevention-of-covid-19-as-post-exposure-prophylaxis.html. Published March 12, 2025. Accessed March 24, 2025.
Shionogi receives U.S. FDA fast track designation for ensitrelvir fumaric acid, an investigational oral antiviral for COVID-19. https://www.shionogi.com/global/en/news/2023/04/20230404.html. Published April 4, 2023. Accessed March 24, 2025.

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Sources/Disclosures

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Source:

Fukushi A, et al. Abstract 200. Presented at: Conference on Retroviruses and Opportunistic Infections; March 9-12, 2025; San Francisco.

Disclosures: Hayden reports being reimbursed for travel and other costs by Shionogi and Hoffman LaRoche, and being paid for review activities by Enanta Pharmaceuticals.