Xocova (ensitrelvir) / Shionogi - LARVOL DELTA

Ensitrelvir in Hospitalized Patients with SARS-CoV-2 During the Omicron Epidemic: A Single-Center Observational Study. (PubMed, Infect Dis Ther) - "Ensitrelvir demonstrated a low day 28 mortality, even among patients with advanced age, immunosuppressive conditions, and moderate to severe COVID-19. These findings may suggest a potential role for ensitrelvir in the treatment of hospitalized patients with COVID-19."

Journal • Observational data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effectiveness of ensitrelvir for cough caused by COVID-19 Omicron variant in patients with asthma. (PubMed, Microbiol Spectr) - "Ensitrelvir was associated with scores that were 3.1 points higher on day 4, 3.5 points higher on day 7, and 2.0 points higher on day 14 compared with symptomatic treatment (P <0.001 for all). Our results demonstrated that early administration of ensitrelvir may be effective as a treatment for cough due to the COVID-19 Omicron variant."

Journal • Asthma • Chronic Cough • Cough • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Ensitrelvir in hospitalised patients with SARS-CoV-2: a single-centre observational study (ESCMID Global 2025) - No abstract available

Clinical • Late-breaking abstract • Observational data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Combination therapy with ensitrelvir and remdesivir reduces viral shedding duration in COVID-19 patients treated with anti-CD20 monoclonal antibodies (ESCMID Global 2025) - No abstract available

Clinical • Combination therapy • Infectious Disease • Novel Coronavirus Disease

Phenotyping and genotyping analysis using baseline swab samples in ensitrelvir clinical studies (ESCMID Global 2025) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease

Ensitrelvir for the prevention of COVID-19 among household contacts: key subgroup analyses of a randomized, double-blinded, placebo controlled post-exposure prophylaxis study, SCORPIO-PEP (ESCMID Global 2025) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease

Real-World Treatment Outcomes in the First and Subsequent Coronavirus Disease 2019 (COVID-19) Hospital Clusters. (PubMed, Cureus) - "Countermeasures against hospital clusters require comprehensive measures, such as infection prevention, vaccination, rapid diagnosis, and antiviral drug administration. Antiviral drugs may shorten hospital clusters by rapidly suppressing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients."

HEOR • Journal • Real-world evidence • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Potent, Pan-Coronavirus Antiviral Activity of the Novel 3CLpro Inhibitor ALG-097558 (CROI 2025) - "Against Omicron subvariants, ALG-097558 is 3- to 9-fold more active than nirmatrelvir (the 3CLpro inhibitor in Paxlovid™). Other 3CLpro inhibitors in clinical development such as ensitrelvir and ibuzatrelvir demonstrated greatly reduced antiviral activity against α-CoVs...Conclusions ALG-097558 demonstrates potent, pan-coronaviral activity in preclinical experiments and is uniquely positioned as a treatment option for SARS-CoV-2 infection and potential future coronavirus pandemics. After having demonstrated a favorable clinical safety and PK profile in Phase I, including ritonavir-free dosing, ALG-097558 warrants further evaluation in patients with COVID-19."

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SARS-CoV-2 Ensitrelvir Resistance-Associated Mutations in Phase III Randomized Clinical Trial (CROI 2025) - "Conclusions Resistance-associated mutations emerged with ensitrelvir treatment, but was relatively infrequent and associated with higher pre-treatment RNA levels. Protease inhibitors represent an important treatment modality for COVID-19, but can be vulnerable to treatment-emergent mutations and additional monitoring is warranted."

Clinical • P3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • SPECC1

Ensitrelvir to Prevent COVID-19 in Households: SCORPIO-PEP Phase III Placebo-Controlled Trial Results (CROI 2025) - "There were no COVID-19 related hospitalizations or fatalities. Conclusions Administration of ensitrelvir to HHC <72 hours after the onset of IP symptoms was effective and generally well tolerated for PEP in HHC, including those with HR factors."

Clinical • Late-breaking abstract • P3 data • Infectious Disease • Influenza • Novel Coronavirus Disease • Pain • Respiratory Diseases

The time to return-to-work in healthcare workers with COVID-19 treated with ensitrelvir, a novel oral inhibitor of 3C-like protease of SARS-CoV-2: An observational study utilizing pre-existing data from a single hospital. (PubMed, J Infect Chemother) - "On the first scheduled date of return-to-work (i.e. the date of first antigen test after onset), 56.7% of participants in the ensitrelvir group and 33.3% in the non-antiviral group had recovered, with the antigen test negativity in 76.7% and 52.4%, respectively. Ensitrelvir treatment for healthcare workers experiencing COVID-19 appeared to be associated with early symptom amelioration with viral load reduction, and shorter time to return-to-work."

Journal • Observational data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Comparative Study of Ensitrelvir and Symptomatic Therapy in Healthcare Workers with Mild COVID-19: A Single Center Retrospective Analysis in Chiba, Japan. (PubMed, J Infect Chemother) - "Ensitrelvir is a safe and effective option for reducing SARS-CoV-2 viral load in HCWs with mild COVID-19, supporting timely recovery and reducing infectivity."

Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

M49L and other drug resistance mutations emerging in individuals after administration of ensitrelvir in Japanese clinical settings. (PubMed, Antiviral Res) - "The current status of drug resistance mutations occurring in individuals following administration of ensitrelvir in Japanese clinical settings was clinically investigated for the first time. Considering that the barrier to resistance to ensitrelvir is lower than that to other antiviral drugs and that M49L is a unique mutation that occurs quickly, tends to become a majority mutation, and is maintained thereafter through its ability to replicate, the spread of strains that have acquired ensitrelvir resistance should be closely monitored."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Antiviral Trials-Navigating the Shifting Sands of a Pandemic. (PubMed, Clin Infect Dis) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial. (PubMed, Clin Infect Dis) - "Despite the evidence of antiviral activity with ensitrelvir, this trial did not demonstrate a significant difference in time to sustained symptom resolution."

Clinical • Journal • P3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Ensitrelvir treatment-emergent amino acid substitutions in SARS-CoV-2 3CLpro detected in the SCORPIO-SR phase 3 trial. (PubMed, Antiviral Res) - "Recombinant viruses with some 3CLpro mutations had reduced susceptibility to ensitrelvir in vitro, with limited effects on viral and competitive fitness. Continued surveillance is warranted to monitor the spread of viruses with 3CLpro mutations."

Journal • P3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • SPECC1

PREVAIL-LC: Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Timothy Henrich | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2025 ➔ Jun 2025

Enrollment closed • Trial primary completion date • Infectious Disease • Inflammation • Novel Coronavirus Disease

Drug-drug interaction between ensitrelvir and tacrolimus in a patient undergoing treatment for COVID-19: a case report. (PubMed, J Pharm Health Care Sci) - "This DDI extended the half-life of TAC by approximately 3.4-fold, an effect that gradually diminished over 7 to 10 days. When patients receiving TAC treatment start ensitrelvir therapy, a dose reduction of TAC by approximately one-third to one-fourth is considered appropriate."

Journal • Immunology • Infectious Disease • Inflammatory Arthritis • Novel Coronavirus Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

An orally available P1'-5-fluorinated Mpro inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier. (PubMed, PNAS Nexus) - "We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (Mpro) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2XBB1.5 and SARS-CoV-2EG.5.1 than two Mpro inhibitors: nirmatrelvir and ensitrelvir. TKB272 shows no apparent genotoxicity as tested in the micro-Ames test. Highly potent TKB272 may serve as a COVID-19 therapeutic, overcome resistance to existing Mpro inhibitors."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Drug-Drug Interaction Study of S-217622 With Combined Oral Contraceptives in Healthy Adult Female Participants (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Shionogi

New P1 trial

Efficacy and safety of antiviral therapies for the treatment of persistent COVID-19 in immunocompromised patients since the Omicron surge: a systematic review. (PubMed, J Antimicrob Chemother) - "Based on very low certainty evidence, combining one direct antiviral with passive immunization resulted in high rates of viral clearance and few recurrences. AEs occurred in cases treated with at least two direct antivirals. Controlled studies are needed."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Ensitrelvir for the treatment of COVID-19: Final analysis of a post-marketing surveillance from Japan. (PubMed, J Infect Chemother) - "This PMS including >3000 patients suggested the safety and effectiveness of ensitrelvir for the treatment of patients with COVID-19 in Japan, with no new safety concern."

Journal • P4 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SARS-CoV-2 Resistance to Small Molecule Inhibitors. (PubMed, Curr Clin Microbiol Rep) - "Antiviral therapies such as Nirmatrelvir and Ensitrelvir focus on inhibiting 3CLpro, whereas Remdesivir, Favipiravir, and Molnupiravir target nsp12, thereby reducing the viral load. This manuscript summarizes mutations in 3CLpro and nsp12, which could potentially reduce the efficacy of drugs. Additionally, it encapsulates recent advancements in small molecule antivirals targeting SARS-CoV-2 viral proteins, including their potential for developing resistance against emerging variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Biological Characterization of AB-343, a Novel and Potent SARS-CoV-2 Mpro Inhibitor with Pan-Coronavirus Activity. (PubMed, Antiviral Res) - "No change in AB-343 potency was observed against Mpro of SARS-CoV-2 variants of concern, including Omicron, suggesting that AB-343 could be developed as a treatment against currently circulating coronaviruses. AB-343 also remained active against several Mpro variants which confer significant resistance to nirmatrelvir and ensitrelvir, which are presently the only Mpro inhibitors authorized for the treatment of COVID-19, further supporting the evaluation of AB-343 as a novel and potent therapeutic for COVID-19 and other coronaviruses."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Clinical Features of Patients with COVID-19 Recurrence During Hospitalization in the Omicron Variant Surge. (PubMed, Infect Drug Resist) - "Of the 7 patients, 6 (85.7%) were initially treated with remdesivir (RDV), but only 3 patients were re-treated with RDV, and the other 4 patients were successfully re-treated with oral 3C-like protease inhibitors, such as ensitrelvir (ESV) and nirmatrelvir/ritonavir (N/R). These data suggest that COVID-19 recurrence was found in patients with hematological disorders, such as lymphoma, and/or patients with no vaccination history. However, these patients were treated successfully by re-administration of anti-SARS-CoV-2 agents, including ESV and N/R."

Journal • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases