Ensitrelvir as a novel treatment option for mild-to-moderate COVID-19: a narrative literature review
To address the coronavirus disease 2019 (COVID-19) pandemic, several antiviral agents targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed for clinical use. However, antivirals that can be administered irrespective of risk factors were lacking until the approval...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2025-04-01
|
| Series: | Therapeutic Advances in Infectious Disease |
| Online Access: | https://doi.org/10.1177/20499361251321724 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850172459100143616 |
|---|---|
| author | Hiroshi Mukae Hiroshi Yotsuyanagi Norio Ohmagari Yohei Doi Masaya Yamato Takumi Imamura Hiroki Sakaguchi Takao Sanaki Takuhiro Sonoyama Yuko Tsuge Takeki Uehara |
| author_facet | Hiroshi Mukae Hiroshi Yotsuyanagi Norio Ohmagari Yohei Doi Masaya Yamato Takumi Imamura Hiroki Sakaguchi Takao Sanaki Takuhiro Sonoyama Yuko Tsuge Takeki Uehara |
| author_sort | Hiroshi Mukae |
| collection | DOAJ |
| description | To address the coronavirus disease 2019 (COVID-19) pandemic, several antiviral agents targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed for clinical use. However, antivirals that can be administered irrespective of risk factors were lacking until the approval of ensitrelvir fumaric acid (hereafter, ensitrelvir) in Japan, which took effect in November 2022. Ensitrelvir is an oral SARS-CoV-2 3C-like protease inhibitor currently approved in Japan and Singapore. This narrative review summarizes preclinical, clinical trial, and real-world data on ensitrelvir. The efficacy and safety of ensitrelvir were assessed in a seamless, randomized, double-blind, placebo-controlled, phase II/III study conducted in Japan, South Korea, and Vietnam (Japan Registry of Clinical Trials identifier, jRCT2031210350). This study enrolled patients with mild-to-moderate COVID-19 symptoms or asymptomatic individuals irrespective of the presence of risk factors for severe illness. Overall, ensitrelvir demonstrated favorable antiviral efficacy and symptom improvement, with an acceptable safety profile. In the phase III part, the time to resolution of the composite of five typical COVID-19 symptoms showed a difference between the ensitrelvir 125 mg and placebo groups, and the difference in median was approximately 1 day when the patients were randomized in less than 72 h of disease onset. This study is one of the clinical trials that used patient symptoms as a clinical efficacy endpoint. Additional clinical trials are currently underway to investigate the efficacy and safety of ensitrelvir in various patient populations. Moreover, published evidence generally supports the effectiveness of ensitrelvir in routine clinical practice and its antiviral activity against various SARS-CoV-2 variants of concern. Further research is granted to establish ensitrelvir as a novel antiviral treatment. Royalty-free licensing agreements concluded between drug manufacturers and the Medicines Patent Pool will facilitate access to COVID-19 therapeutics, including ensitrelvir, in low- and middle-income countries. |
| format | Article |
| id | doaj-art-0b6d6db760fb46ef8a971d6d9947c24f |
| institution | OA Journals |
| issn | 2049-937X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Infectious Disease |
| spelling | doaj-art-0b6d6db760fb46ef8a971d6d9947c24f2025-08-20T02:20:05ZengSAGE PublishingTherapeutic Advances in Infectious Disease2049-937X2025-04-011210.1177/20499361251321724Ensitrelvir as a novel treatment option for mild-to-moderate COVID-19: a narrative literature reviewHiroshi MukaeHiroshi YotsuyanagiNorio OhmagariYohei DoiMasaya YamatoTakumi ImamuraHiroki SakaguchiTakao SanakiTakuhiro SonoyamaYuko TsugeTakeki UeharaTo address the coronavirus disease 2019 (COVID-19) pandemic, several antiviral agents targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed for clinical use. However, antivirals that can be administered irrespective of risk factors were lacking until the approval of ensitrelvir fumaric acid (hereafter, ensitrelvir) in Japan, which took effect in November 2022. Ensitrelvir is an oral SARS-CoV-2 3C-like protease inhibitor currently approved in Japan and Singapore. This narrative review summarizes preclinical, clinical trial, and real-world data on ensitrelvir. The efficacy and safety of ensitrelvir were assessed in a seamless, randomized, double-blind, placebo-controlled, phase II/III study conducted in Japan, South Korea, and Vietnam (Japan Registry of Clinical Trials identifier, jRCT2031210350). This study enrolled patients with mild-to-moderate COVID-19 symptoms or asymptomatic individuals irrespective of the presence of risk factors for severe illness. Overall, ensitrelvir demonstrated favorable antiviral efficacy and symptom improvement, with an acceptable safety profile. In the phase III part, the time to resolution of the composite of five typical COVID-19 symptoms showed a difference between the ensitrelvir 125 mg and placebo groups, and the difference in median was approximately 1 day when the patients were randomized in less than 72 h of disease onset. This study is one of the clinical trials that used patient symptoms as a clinical efficacy endpoint. Additional clinical trials are currently underway to investigate the efficacy and safety of ensitrelvir in various patient populations. Moreover, published evidence generally supports the effectiveness of ensitrelvir in routine clinical practice and its antiviral activity against various SARS-CoV-2 variants of concern. Further research is granted to establish ensitrelvir as a novel antiviral treatment. Royalty-free licensing agreements concluded between drug manufacturers and the Medicines Patent Pool will facilitate access to COVID-19 therapeutics, including ensitrelvir, in low- and middle-income countries.https://doi.org/10.1177/20499361251321724 |
| spellingShingle | Hiroshi Mukae Hiroshi Yotsuyanagi Norio Ohmagari Yohei Doi Masaya Yamato Takumi Imamura Hiroki Sakaguchi Takao Sanaki Takuhiro Sonoyama Yuko Tsuge Takeki Uehara Ensitrelvir as a novel treatment option for mild-to-moderate COVID-19: a narrative literature review Therapeutic Advances in Infectious Disease |
| title | Ensitrelvir as a novel treatment option for mild-to-moderate COVID-19: a narrative literature review |
| title_full | Ensitrelvir as a novel treatment option for mild-to-moderate COVID-19: a narrative literature review |
| title_fullStr | Ensitrelvir as a novel treatment option for mild-to-moderate COVID-19: a narrative literature review |
| title_full_unstemmed | Ensitrelvir as a novel treatment option for mild-to-moderate COVID-19: a narrative literature review |
| title_short | Ensitrelvir as a novel treatment option for mild-to-moderate COVID-19: a narrative literature review |
| title_sort | ensitrelvir as a novel treatment option for mild to moderate covid 19 a narrative literature review |
| url | https://doi.org/10.1177/20499361251321724 |
| work_keys_str_mv | AT hiroshimukae ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview AT hiroshiyotsuyanagi ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview AT norioohmagari ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview AT yoheidoi ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview AT masayayamato ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview AT takumiimamura ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview AT hirokisakaguchi ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview AT takaosanaki ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview AT takuhirosonoyama ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview AT yukotsuge ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview AT takekiuehara ensitrelvirasanoveltreatmentoptionformildtomoderatecovid19anarrativeliteraturereview |