Ensitrelvir, sold under the brand name Xocova is an

antiviral medication Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobial ...

used as a treatment for

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...

. It was developed by

Shionogi is a Japanese pharmaceutical company best known for developing Crestor. Medical supply and brand name also uses katakana (シオノギ). Shionogi has business roots that date back to 1878, and was incorporated in 1919. Among the medicines pr ...

in partnership with

Hokkaido University , or , is a public research university in Sapporo, Hokkaido, Japan. Founded in 1918, it is the fifth-oldest government-authorised university in Japan and one of the former Imperial Universities. The university finds its roots in Sapporo A ...

and acts as an orally active 3C-like protease inhibitor. It is taken by mouth. The most common

adverse event In pharmaceuticals, an adverse event (AE) is any unexpected or harmful medical occurrence that happens to a patient during medical treatment or a clinical trial. Unlike direct side effects, an adverse event does not necessarily mean the medicati ...

s include transient decreases in

high-density lipoprotein High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...

and increased

blood triglycerides Blood lipids (or blood fats) are lipids in the blood, either free or bound to other molecules. They are mostly transported in a phospholipid capsule, and the type of protein embedded in this outer shell determines the fate of the particle and its ...

Medical uses

Ensitrelvir is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of

History

, ensitrelvir had reached Phase III

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s. 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, including

remdesivir Remdesivir, sold under the brand name Veklury, Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. is a Broad-spectrum antiviral drug, broad-spectrum ...

and

molnupiravir Molnupiravir, sold under the brand name Lagevrio, is an antiviral medication that inhibits the replication of certain RNA viruses. It is used to treat COVID19 in those infected by SARS-CoV-2. It is taken by mouth. Molnupiravir is a prodrug o ...

. In a study of 428 patients, viral load was reduced, but symptoms were not significantly reduced. In February 2022, the company sought emergency approval from regulators in Japan. 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. Ensitrelvir may be effective in treating smell and taste loss from COVID-19 infection. In a 2023 study, the drug was associated with a 39% reduction in these symptoms.

Society and culture

Legal status

Ensitrelvir was approved for emergency use in Japan in November 2022, before gaining full approval in March 2024. It was approved in Singapore in November 2023. In April 2023, ensitrelvir was given a "

Fast Track Fast Track, Fast track, or Fasttrack may refer to: Processes and systems * Fast track (FDA), a U.S. Food and Drug Administration expedited review program * Fast track (trade), the authority of the U.S. President to broker trade agreements with lim ...

" designation from the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

Names

Ensitrelvir is the international nonproprietary name (INN).

Research

Ensitrelvir has been investigated for use as potential

post-exposure prophylaxis Post-exposure prophylaxis, also known as post-exposure prevention (PEP), is any preventive medical treatment started after exposure to a pathogen in order to prevent the infection from occurring. It should be contrasted with pre-exposure prophy ...

(PEP) for SARS-CoV-2 infection. 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. 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. An April 2024 pre-clinical study in a mouse model investigating ensitrelvir demonstrated its potential use as a pre-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. 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. 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. 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.

References

{{Authority control Antiviral drugs COVID-19 drug development Fluoroarenes Indazoles Chloroarenes SARS-CoV-2 main protease inhibitors Triazoles