Inavir (laninamivir) / Daiichi Sankyo, Vaxart - LARVOL DELTA

How to manage antivirals in critically ill patients with Influenza? (PubMed, Clin Microbiol Infect) - "Neuraminidase inhibitors constitute the vast majority of antivirals currently prescribed for influenza. The most commonly prescribed NAI to date is oseltamivir. While its efficacy in non-severe cases of influenza is well established, the evidence for its efficacy in critically ill patients is based on less robust studies, as no randomised controlled trials have been conducted in this population. Limited data on oseltamivir pharmacokinetics is available in critically ill patients. The selection of A(H1N1)pdm09 resistant variants to oseltamivir is particularly problematic in critically-ill patients hospitalised in intensive care units. Data on other antivirals, including NAIs (i.e., zanamivir, peramivir and laninamivir) or baloxavir marboxil in critically ill patients are scarce. Further research is needed to develop new drugs and assess their efficacy in critically ill patients and to better assess the effect of oseltamivir in this population."

Journal • Review • Critical care • Infectious Disease • Influenza • Respiratory Diseases

Antiviral Susceptibility of Influenza A(H5N1) Clade 2.3.2.1c and 2.3.4.4b Viruses from Humans, 2023-2024. (PubMed, Emerg Infect Dis) - "In the neuraminidase inhibition assay, all viruses displayed susceptibility to neuraminidase inhibitor antiviral drugs oseltamivir, zanamivir, peramivir, laninamivir, and AV5080...All viruses were susceptible to polymerase inhibitors baloxavir and tivoxavir and to polymerase basic 2 inhibitor pimodivir with 50% effective concentrations in low nanomolar ranges. Because drug-resistant viruses can emerge spontaneously or by reassortment, close monitoring of antiviral susceptibility of H5N1 viruses collected from animals and humans by using sequence-based analysis supplemented with phenotypic testing is essential."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Incidence of Severe Illness in Pediatric Influenza Outpatients Treated with Baloxavir or Neuraminidase Inhibitors. (PubMed, J Infect Chemother) - "Using a large, Japanese health insurance claims database, a lower rate of hospitalization was demonstrated in children aged 5-11 years with an influenza virus infection when treated with baloxavir vs neuraminidase inhibitors. Thus, single dose, oral baloxavir may reduce the incidence of severe illness in these patients."

Journal • Infectious Disease • Influenza • Pediatrics • Respiratory Diseases

In vitro neuraminidase inhibitory concentrations (IC50) of four neuraminidase inhibitors in the Japanese 2023-24 season: Comparison with the 2010-11 to 2022-23 seasons. (PubMed, J Infect Chemother) - "These results indicate that susceptibility to these four NAIs has been maintained across the three influenza types/subtypes over the past fourteen seasons in Japan."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases

Pharmacologic background and clinical issue of anti-influenza drugs. (PubMed, Fukushima J Med Sci) - "Since 2000, rapid antigen detection kits and anti-influenza drugs have been used for the early diagnosis and treatment of influenza in Japan, respectively.　The main drugs available in clinical practice are the neuraminidase inhibitors oseltamivir, zanamivir, laninamivir, and peramivir, as well as the cap-dependent endonuclease inhibitor baloxavir marboxil.　Antiviral therapy with neuraminidase inhibitors has been practiced for many years, especially in Japan; it can shorten the febrile period and reduce complications.　Despite having similar structures, the pharmacologic background of neuraminidase inhibitors differs significantly, as reflected in their varying clinical efficacy.　Due to its inhibitory mechanism, baloxavir marboxil can rapidly reduce the viral load than neuraminidase inhibitors.　However, the duration of symptoms was similar after the administration of baloxavir marboxil and oseltamivir, and variants with reduced drug susceptibility have been detected in..."

Journal • Infectious Disease • Influenza • Pediatrics • Respiratory Diseases

A Pharmacoeconomic Study of Post-Exposure Prophylaxis Strategies for Influenza Virus Infections in Japan. (PubMed, Adv Ther) - "Baloxavir marboxil and oseltamivir are cost-effective prophylactic agents for flu from the perspective of healthcare costs in Japan. This strategy to select baloxavir marboxil or oseltamivir would be helpful to manage a formulary for post-exposure prophylaxis in Japan."

HEOR • Journal • Infectious Disease • Influenza • Respiratory Diseases

In persons exposed to influenza, zanamivir, oseltamivir, laninamivir, and baloxavir reduce symptomatic seasonal influenza. (PubMed, Ann Intern Med) - "2024;404:764-772. 39181596."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Virological and Clinical Outcomes of Influenza Outpatients Treated With Baloxavir, Oseltamivir, or Laninamivir in the 2023-2024 Season. (PubMed, Influenza Other Respir Viruses) - "Baloxavir-resistant variants were not detected in influenza BV before treatment, as with A. The emergence of PA-AA-substituted influenza A after baloxavir administration was temporal and did not cause prolonged symptoms. No baloxavir-resistant BV variants were observed after baloxavir administration."

Clinical data • Journal • Observational data • Infectious Disease • Influenza • Respiratory Diseases

The Synergistic Effect of Baloxavir and Neuraminidase Inhibitors against Influenza Viruses In Vitro. (PubMed, Viruses) - "Oseltamivir, a neuraminidase inhibitor, is a first-line anti-influenza drug, and baloxavir is part of the newest generation of anti-influenza drugs that targets the viral polymerase. The combination of baloxavir with NAIs led to significant synergistic effects; however, the combination of baloxavir with laninamivir failed to result in a synergistic effect on influenza B viruses. Considering the rapid emergence of drug resistance to baloxavir, we believe that these results will be beneficial for combined drug use against influenza."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases

Identification of Potential Tryptase Inhibitors from FDA-Approved Drugs Using Machine Learning, Molecular Docking, and Experimental Validation. (PubMed, ACS Omega) - "Our results demonstrated that several FDA-approved drugs, including landiolol, laninamivir, and cidofovir, significantly inhibited tryptase activity. These findings not only underscore the potential of ML in accelerating drug repurposing but also highlight the feasibility of this approach in identifying effective tryptase inhibitors. This research contributes to the field of drug discovery, offering a novel pathway to expedite the development of therapeutics for tryptase-related pathologies."

FDA event • Journal • Machine learning • Allergy • Hematological Malignancies • Leukemia • Oncology

Occurrence and environmental fate of anti-influenza drugs in a subcatchment of the Yodo River Basin, Japan. (PubMed, Sci Total Environ) - "In this study, the behaviour of the prodrug baloxavir marboxil (BALM)-the active ingredient of Xofluza, an increasingly popular anti-influenza drug-and its pharmacologically active metabolite baloxavir (BAL) in the aquatic environment was evaluated. Additionally, their presence in urban rivers and a wastewater treatment plant (WWTP) in the Yodo River basin was investigated and compared with those of the major anti-influenza drugs used to date (favipiravir (FAV), peramivir (PER), laninamivir (LAN), and its active metabolite, laninamivir octanoate (LANO), oseltamivir (OSE), and its active metabolite, oseltamivir carboxylate (OSEC), and zanamivir (ZAN)) to comprehensively assess their environmental fate in the aquatic environment...Notably, all anti-influenza drugs were effectively removed by ozonation (>90-99.9 % removal) after biological treatment at a WWTP. Thus, these findings suggest the importance of introducing ozonation to reduce pollution loads in rivers and the..."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis. (PubMed, Lancet) - "Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans."

Clinical • Journal • Retrospective data • Review • Infectious Disease • Influenza • Respiratory Diseases

Antiviral susceptibility of SARS-CoV-2 and influenza viruses from 3 co-infected pediatric patients. (PubMed, Int J Infect Dis) - "We evaluated the susceptibility of SARS-CoV-2 against RNA-dependent RNA polymerase inhibitors (remdesivir and molnupiravir) and 3C-like protease inhibitors (nirmatrelvir and ensitrelvir), and that of influenza viruses against neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, and laninamivir) and the cap-dependent endonuclease inhibitor baloxavir...The patients were treated with anti-influenza drugs and did not develop severe symptoms despite the co-infection. Since SARS-CoV-2 and influenza viruses continue to evolve, continuous monitoring of their circulation remains essential to assess public health measures and support clinical management."

Journal • Infectious Disease • Influenza • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases

Treating influenza with neuraminidase inhibitors: an update of the literature. (PubMed, Expert Opin Pharmacother) - "While the prevalence of influenza virus resistance to NAIs remains low, there is heightened vigilance due to the pandemic potential of influenza. Several novel NAIs and derivatives are currently under assessment at various stages of development for the treatment and prevention of influenza."

Journal • Review • Infectious Disease • Influenza • Respiratory Diseases

Duration of fever in children infected with influenza A(H1N1)pdm09, A(H3N2) or B virus and treated with baloxavir marboxil, oseltamivir, laninamivir, or zanamivir in Japan during the 2012-2013 and 2019-2020 influenza seasons. (PubMed, Antiviral Res) - "For influenza B, baloxavir shortened the fever duration by approximately 15 h than NAIs (20.3, 35.0, 34.3, and 34.1 h), as supported by uni- and multivariable analyses. Baloxavir seems to have comparable clinical effectiveness with NAIs on influenza A but can be more effective for treating pediatric influenza B virus infections than NAIs."

Journal • Infectious Disease • Influenza • Pediatrics • Respiratory Diseases • ST6GAL1

AD ASTRA: A Phase 2 Trial Comparing Antiviral Treatments in Early Symptomatic Influenza (clinicaltrials.gov) - P2 | N=3000 | Recruiting | Sponsor: University of Oxford | N=250 ➔ 3000 | Trial completion date: Jan 2025 ➔ Jan 2027 | Trial primary completion date: Dec 2024 ➔ Jan 2027

Enrollment change • Trial completion date • Trial primary completion date • Infectious Disease • Influenza • Respiratory Diseases

Pharmacoeconomic study of anti-influenza virus drugs in Japan based on a network meta-analysis. (PubMed, J Antimicrob Chemother) - "This study thus reaffirms oseltamivir's position as the most cost-effective neuraminidase inhibitor for the treatment of influenza virus infections in Japan from the perspective of healthcare payment. These findings can help decision makers and healthcare providers in Japan."

HEOR • Journal • Retrospective data • Infectious Disease • Influenza • Respiratory Diseases

Synthesis of Rupestonic Acid L-Ephedrine Derivatives with Preliminary In vitro Anti-influenza Viral Activity. (PubMed, Curr Pharm Des) - "The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized and characterized using 1H NMR and 13C NMR. Moreover, their purity was determined by HPLC. Both compounds A and B exhibited more potent activities against the strains of A/PR/8/34 (H1N1) and A/FM/1/47 (H1N1) than rupestonic acid. Compound A can be regarded as a very promising lead compound for the development of anti-influenza inhibitors. Based on these results, more rupestonic acid derivatives will be designed and synthesized in the future for the development of anti-influenza inhibitors."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases

Impact of the H274Y Substitution on N1, N4, N5, and N8 Neuraminidase Enzymatic Properties and Expression in Reverse Genetic Influenza A Viruses. (PubMed, Viruses) - "The H274Y-NA substitution resulted in highly reduced inhibition by oseltamivir and normal inhibition by zanamivir and laninamivir...In conclusion, the H274Y-NA substitution of different group-1-NAs systematically reduced their affinity for MUNANA substrate without a significant impact on NA Vm. The impact of the H274Y-NA substitution on viral NA expression was different according to the studied NA."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Unveiling the Potent Antiviral and Antioxidant Activities of an Aqueous Extract from Caesalpinia mimosoides Lamk: Cheminformatics and Molecular Docking Approaches. (PubMed, Foods) - "Molecular docking suggested that GA interacts with conserved residues (e.g., Arg152 and Asp151) located in the catalytic inner shell of the viral neuraminidase (NA), sharing the same pocket as those of anti-neuraminidase drugs, such as laninamivir and oseltamivir. Additionally, other metabolites were also found to potentially interact with the active site and the hydrophobic 430-cavity of the viral surface protein, suggesting a possibly synergistic effect of various phytochemicals. Therefore, the C. mimosoides aqueous extract may be a good candidate for coping with increasing influenza virus resistance to existing antivirals."

Journal • Infectious Disease • Influenza • Oncology • Respiratory Diseases

Visualizing intracellular sialidase activity of influenza A virus neuraminidase using a fluorescence imaging probe. (PubMed, J Virol Methods) - "Importantly, we observed that laninamivir octanoate effectively inhibited the intracellular viral NA, in contrast to drugs like zanamivir or laninamivir. Our study establishes a visualization protocol for intracellular viral NA sialidase activity and visualizes the inhibitory effect of laninamivir octanoate on Golgi-localized intracellular viral NA in infected cells."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Prescription of anti-influenza drugs in Japan, 2014-2020: A retrospective study using open data from the national claims database. (PubMed, PLoS One) - "Based on our clarification of how influenza is clinically managed in Japan, future work should evaluate the clinical and economic aspects of proactively prescribing anti-influenza drugs."

Claims database • Journal • Retrospective data • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

In vitro neuraminidase inhibitory concentrations (IC) of four neuraminidase inhibitors in the Japanese 2022-23 season: Comparison with the 2010-11 to 2019-20 seasons. (PubMed, J Infect Chemother) - "To assess the extent of susceptibility to the four neuraminidase inhibitors (NAIs) approved in Japan of the epidemic viruses in the 2022-23 influenza season in Japan, we measured the 50 % inhibitory concentration (IC) of oseltamivir, zanamivir, peramivir, and laninamivir in influenza virus isolates from patients...No A(H3N2) with highly reduced sensitivity to any of the NAIs was found in the 2022-23 season prior to or after drug administration. These results indicate that the sensitivity to these four commonly used NAIs has been maintained, at least for A(H3N2), in the 2022-23 influenza season in Japan, after the 2020-21 and 2021-22 seasons when the prevalence of influenza was extremely low."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases

Rapid health technology assessment of the novel endonuclease inhibitor baloxavir for the treatment of influenza. (PubMed, J Chemother) - "In terms of efficacy, baloxavir had an advantage over oseltamivir for all three types of influenza patients (otherwise healthy patients, high-risk patients, and patients are not separated into groups with and without underlying health conditions) concerning change in virus titer from baseline at 24 and 48 h; about otherwise healthy patients and high-risk patients, baloxavir had an advantage over peramivir; pertaining to high-risk patients, baloxavir had an advantage over laninamivir; the above differences between groups were all statistically significant. Economically, in Japanese adult influenza patients and high-risk populations, the Quality-Adjusted Life Years (QALY) of baloxavir slightly triumphed over that of laninamivir (Δ = 0.000112 and 0.00209 QALY per 1 patient, respectively); moreover, the incremental cost-effectiveness ratio (ICER: 2,231,260 and 68,855 yen/QALY, respectively) was below the willingness-to-pay (WTP) threshold (5,000,000 yen/QALY); in Chinese..."

Journal • Review • Infectious Disease • Influenza • Respiratory Diseases

Microsecond dynamics of H10N7 influenza neuraminidase reveals the plasticity of loop regions and drug resistance due to the R292K mutation. (PubMed, J Comput Chem) - "Here, we investigated the structural dynamics of neuraminidase N7 upon binding of inhibitors, and the drug resistance mechanisms against the oseltamivir (OTV) and laninamivir (LNV) antivirals due to the crucial R292K mutation on the N7 using the computational microscope, molecular dynamics (MD) simulations. Due to the broader binding pocket cavity of the smaller K292 mutant residue relative to the wildtype, the drug carboxylate to K292 hydrogen bonding was lost, and the area surrounding the K292 residue was more accessible to water molecules. This implies that drug resistance could be reduced by strengthening the hydrogen bond contacts between N7 inhibitors and altered N7, creating inhibitors that can form a hydrogen bond to the mutant K292, or preserving the closed cavity conformations."

Journal • Infectious Disease • Influenza • Respiratory Diseases