Baloxavir Marboxil: An Original New Drug against Influenza

Dufrasne, François

doi:10.3390/ph15010028

Cited by 24 publications

(12 citation statements)

References 27 publications

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“…Additional considerations include the combination of NAI with a second antiviral drug that exhibits a different mechanism of action, such as baloxavir, which has been licensed for influenza A and B viruses infections in patients > 12 years in Japan and United states since 2018 [ 40 ]. Baloxavir marboxil (S-033188) is the small-molecule prodrug of the selective polymerase acidic protein inhibitor S-033447 and inhibits the cap-dependent endonuclease and prevents viral transcription [ 41 ]. A study with 366 patients, 87% of whom had influenza A virus infection, combining baloxavir with NAIs (oseltamivir, zanamivir, and peramivir) did not result in superior clinical outcomes compared with NAIs alone [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of Complicated Influenza A(H3N2) Virus Infection and Rhabdomyolysis with Compassionate Use of IV Zanamivir

et al. 2023

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In 2019, EMA licensed intravenous (IV) zanamivir for severe influenza virus infection in children over 6 months as well as adults. Prior to that, it was possible via a compassionate use program. We present successful compassionate use of IV zanamivir in a 14-year-old female with severe influenza A(H3N2) and multi-organ failure, who had failed oral oseltamivir. Her illness was complicated by acute respiratory distress syndrome and rhabdomyolysis requiring extracorporeal membrane oxygenation and hemofiltration. Considering the broad safety margins with neuraminidase inhibitors, an adult dose of 600 mg IV BID was administered in this 60 kg patient. Influenza virus was cleared rapidly and undetectable on day 13. Creatine kinase (CK) values were dropping from 38,000 to 500 within nine days. Given the recent licensure of IV zanamivir, multi-center prospective observational studies in pediatric Intensive Care Unit patients would be beneficial to guide the most appropriate use of IV zanamivir in this vulnerable age group.

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Section: Discussionmentioning

confidence: 99%

Successful Treatment of Complicated Influenza A(H3N2) Virus Infection and Rhabdomyolysis with Compassionate Use of IV Zanamivir

et al. 2023

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“…In this study, the most commonly prescribed antiviral medication was baloxavir marboxil, potentially because unlike earlier drugs, this most recently approved antiviral has the advantage of a single-dose regimen [ 38 ]. A test-and-treat strategy using a more accurate PCR-based test could increase the appropriate and judicious prescription of anti-influenza medication, and may also reduce unnecessary antibiotic use that can increase the risk of antibiotic resistance and lead to common side effects [ 20 , 39 – 45 ].…”

Section: Discussionmentioning

confidence: 99%

Comparing the cobas Influenza A/B Nucleic acid test for use on the cobas Liat System (Liat) with rapid antigen tests for clinical management of Japanese patients at the point of care

Mikamo

Koizumi²,

Yamagishi³

et al. 2022

PLoS ONE

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Background Rapid diagnosis of influenza is critical in preventing the spread of infection and ensuring patients quickly receive antiviral medication to reduce the severity and duration of influenza symptoms, whilst controlling the spread of the causative virus. In Japan patients are often administered anti-influenza medication following a positive rapid antigen detection test (RADT) result. However, the sensitivity of RADTs can lead to false negative results. The cobas® Influenza A/B Nucleic acid test for use on the cobas Liat® System (Liat) is a molecular point-of-care method that can provide a more sensitive alternative to RADTs for rapid influenza diagnosis and treatment. Methods In this prospective multicenter study, diagnostic performance of the Liat test was compared with RADTs in patients presenting with influenza-like-illness. Test performance was also assessed by time since symptom onset. Results Of 419 patients enrolled, 413 were evaluable for all designated tests. Most patients had type-A infection, and only one patient had influenza type B. In 413 patients, the sensitivity and specificity (95% CI) of the Liat test were 99.5% (97.2–99.9%) and 99.5% (97.4–99.9%), respectively, and were 79.7% (73.5–84.7%) and 95.4% (91.7–97.5%) for RADTs. For patients tested <12 hours from symptom onset, the Liat test had significantly higher sensitivity than RADTs (p<0.0001). Conclusion Overall, compared with standard of care RADTs, the Liat test was more sensitive and specific in children and adults, particularly in the early stages of infection. Greater sensitivity can enable earlier diagnosis and may better inform appropriate antiviral treatment decisions.

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“…At present, the PA inhibitor baloxavir marboxil, jointly developed by Shionogi and Roche, is used for the treatment of influenza A and B in individuals over the age of 12 [ 58 ]. Since there is no similar mechanism and corresponding protease in host cells, baloxavir acts as a novel CAP-dependent nucleic acid endonuclease inhibitor, and can selectively block the transcription process of the influenza virus without affecting host cells [ 59 , 60 ].…”

Section: Viral Dna/rna Synthases Inhibitorsmentioning

confidence: 99%

Progression of Antiviral Agents Targeting Viral Polymerases

Peng

Wang

et al. 2022

Molecules

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Viral DNA and RNA polymerases are two kinds of very important enzymes that synthesize the genetic materials of the virus itself, and they have become extremely favorable targets for the development of antiviral drugs because of their relatively conserved characteristics. There are many similarities in the structure and function of different viral polymerases, so inhibitors designed for a certain viral polymerase have acted as effective universal inhibitors on other types of viruses. The present review describes the development of classical antiviral drugs targeting polymerases, summarizes a variety of viral polymerase inhibitors from the perspective of chemically synthesized drugs and natural product drugs, describes novel approaches, and proposes promising development strategies for antiviral drugs.

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Baloxavir Marboxil: An Original New Drug against Influenza

Cited by 24 publications

References 27 publications

Successful Treatment of Complicated Influenza A(H3N2) Virus Infection and Rhabdomyolysis with Compassionate Use of IV Zanamivir

Successful Treatment of Complicated Influenza A(H3N2) Virus Infection and Rhabdomyolysis with Compassionate Use of IV Zanamivir

Comparing the cobas Influenza A/B Nucleic acid test for use on the cobas Liat System (Liat) with rapid antigen tests for clinical management of Japanese patients at the point of care

Progression of Antiviral Agents Targeting Viral Polymerases

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