Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomised, placebo-controlled, phase 3 trial

Efficacy and safety of baloxavir marboxil versus neuraminidase inhibitors in the treatment of influenza virus infection in high-risk and uncomplicated patients – a Bayesian network meta-analysis

“…Baloxavir, with its high antiviral activity, serves a promising option in the treatment of patients with influenza., however human-to-human transmission was detected in 5 patients in the antiviral resistance surveillance in Japan in 2018/2019 and it needs to be continuously monitored through the surveillance [19]. Substitutions of the 38 th amino acid position in polymerase acidic protein conferring reduced baloxavir susceptibility emerged in 2.2% and 9.7% of patients in phase 2 and phase 3 of CAPSTONE-1 trial respectively, as well as in 5.2% of patients in phase 3 CAPSTONE-2 trial [13,14] There are some potential limitations caused by considering studies that enrolled patients with a wide range of risk factors, as well as studies with single risk factors that may result in potential heterogeneity and inconsistency within the network of evidence in this analysis. The comparability of these populations was confirmed by the clinical expert.…”

“…The median time to cessation of viral shedding in baloxavir patients was 48 hours -significantly less than 96 hours in both the placebo and oseltamivir patients. Baloxavir compared with the placebo reduced the frequency of influenza-related complications (2.8% and 10.4%) and the need for systemic antibiotic use (3.4% vs 7.5%) [14]. A recent network meta-analysis by Taieb et al demonstrated that in the otherwise healthy (OwH) population, baloxavir was associated with a reduced time to alleviation of all symptoms compared to zanamivir, whereas time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir [15].…”

Evaluating the fitness of PA/I38T-substituted influenza A viruses with reduced baloxavir susceptibility in a competitive mixtures ferret model

“…Human clinical trial data have shown that a single oral baloxavir dose alleviates influenza symptoms at least as effectively as a 5-day oral course of twice-daily oseltamivir, as well as suppressing viral shedding more rapidly in all patient populations examined (Baker et al, 2020; Hayden et al, 2018; Hirotsu et al, 2019; Ison et al, 2020). In 9.7% of otherwise-healthy patients treated with baloxavir in the phase 3 CAPSTONE-1 trial, viruses with amino acid substitutions at residue I38 of the PA protein were identified.…”

“…Although based on small patient numbers, post-hoc analyses of the phase 3 CAPSTONE-1 trial suggested these variants can be associated with prolonged virus detection and uncommonly with symptom rebound (Uehara et al, 2019). However, analysis of the CAPSTONE-2 trial (patients at high risk of complications) showed the opposite effect, whereby I38X variants were associated with numerically faster resolution of symptoms than those without (Ison et al, 2020), suggesting further investigation into the clinical impact of I38X variants is required.…”

Novel respiratory infectious diseases in Korea

“…A significant reduction in viral load was observed a day after taking the drug compared with placebo or oseltamivir administration [ 16 ]. In addition, a single oral dose of baloxavir marboxil had a similar effect as oseltamivir in relieving influenza symptoms in high-risk outpatients and children [ 17 , 18 ].…”