As of 2022[update], ensitrelvir had reached Phase IIIclinical trials.[12] The Japanese government is reportedly considering allowing Shionogi permission to apply for approval for medical use before the final steps of trials are completed, potentially speeding up the release for sale. This conditional early approval system has previously been used in Japan to accelerate the progression to market of other antiviral drugs targeting COVID-19, includingremdesivir andmolnupiravir.[13] In a study of 428 patients, viral load was reduced, but symptoms were not significantly reduced.[14]
In February 2022, the company sought emergency approval from regulators in Japan.[4][14]
Shionogi announced they had reached a preliminary agreement to supply 1million doses to the Japanese government once the drug is approved. The CEO said they could have capacity to make 10million doses a year.[15]
Ensitrelvir may be effective in treatingsmell and taste loss from COVID-19 infection. In a 2023 study, the drug was associated with a 39% reduction in these symptoms.[16]
Ensitrelvir was approved for emergency use in Japan in November 2022,[9][4][5] before gaining full approval in March 2024.[1] It was approved in Singapore in November 2023.[17]
Ensitrelvir has been investigated for use as potentialpost-exposure prophylaxis (PEP) for SARS-CoV-2 infection.[20][21] The SCORPIO-PEP trial, a global Phase 3 study, assessed the safety and efficacy of ensitrelvir in preventing symptomatic COVID-19 among household contacts of individuals with confirmed SARS-CoV-2 infection.[21][22][23][24] Top-line results from this trial suggested that use of ensitrelvir as post-exposure prophylaxis may significantly reduce the risk of symptomatic COVID-19 infection in exposed household contacts compared to placebo.[25][26][27]
An April 2024 pre-clinical study in a mouse model investigating ensitrelvir demonstrated its potential use as apre-exposure prophylactic (PrEP) against developing COVID-19. When administered 24 hours before viral exposure, a single dose of ensitrelvir significantly increased survival rates, inhibited weight loss, and suppressed viral replication in aged mice.[28]
A retrospective study conducted between November 2022 and July 2023 using a large Japanese health insurance database suggested that ensitrelvir may be effective in reducing hospitalization risk in outpatients at high risk for severe COVID-19. The study found a significantly lower risk of hospitalization and a reduced need for respiratory monitoring and oxygen therapy in the ensitrelvir group compared to the control group.[29] In addition, other clinical study shows that early ensitrelvir treatment resulted in rapid symptom relief and significant viral load reduction, with no adverse events, viral rebound, or PASC symptoms, demonstrating its potential efficacy and safety.[30]
In May 2024, Shionogi announced that in a phase 3 trial (SCORPIO-HR), ensitrelvir did not achieve its primary endpoint of a statistically significant reduction in the time to sustained resolution of 15 common COVID-19 symptoms compared to placebo. However, the drug did meet key secondary endpoints, including demonstrating a significant reduction in viral RNA levels, a shorter time to achieve the first negative infectious viral titer in nasal swabs compared to placebo, and a shorter resolution time of 6 symptoms.[31]
^World Health Organization (2022). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 88".WHO Drug Information.36 (3): 89.hdl:10665/363551.
^"Studies Currently Enrolling".University of Kansas Medical Center. Archived fromthe original on 28 October 2023. Retrieved28 October 2023.SCORPIO-PEP is a 28-day study to assess the prevention of COVID-19 infection in those who have been exposed through household contact.
.svg)