Baloxavir Marboxil Single-dose Treatment in Influenza-infected Children

Abstract

Background: Baloxavir marboxil (baloxavir) is a novel, cap-dependent endonuclease inhibitor that has previously demonstrated efficacy in the treatment of influenza in adults and adolescents. We assessed the safety and efficacy of baloxavir in otherwise healthy children with acute influenza. Methods: MiniSTONE-2 ( Clinicaltrials.gov : NCT03629184) was a double-blind, randomized, active controlled trial enrolling children 1–<12 years old with a clinical diagnosis of influenza. Children were randomized 2:1 to receive either a single dose of oral baloxavir or oral oseltamivir twice daily for 5 days. The primary endpoint was incidence, severity and timing of adverse events (AEs); efficacy was a secondary endpoint. Results: In total, 173 children were randomized and dosed, 115 to the baloxavir group and 58 to the oseltamivir group. Characteristics of participants were similar between treatment groups. Overall, 122 AEs were reported in 84 (48.6%) children. Incidence of AEs was similar between baloxavir and oseltamivir groups (46.1% vs. 53.4%, respectively). The most common AEs were gastrointestinal (vomiting/diarrhea) in both groups [baloxavir: 12 children (10.4%); oseltamivir: 10 children (17.2%)]. No deaths, serious AEs or hospitalizations were reported. Median time (95% confidence interval) to alleviation of signs and symptoms of influenza was similar between groups: 138.1 (116.6–163.2) hours with baloxavir versus 150.0 (115.0–165.7) hours with oseltamivir. Conclusions: Oral baloxavir is well tolerated and effective at alleviating symptoms in otherwise healthy children with acute influenza. Baloxavir provides a new therapeutic option with a simple oral dosing regimen.

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.…”

Interactions of Influenza and SARS-CoV-2 with the Lung Endothelium: Similarities, Differences, and Implications for Therapy

“…Current treatment options for both influenza and SARS-CoV-2 remain limited. For influenza, antivirals such as neuraminidase inhibitors (Oseltamivir) and a cap-dependent endonuclease inhibitor (Baloxavir marboxil) are currently used for treatment [ 137 , 138 , 139 ]. Both drugs act by directly inhibiting viral proteins.…”

Pharmacotherapy for acute respiratory infections caused by influenza viruses: current possibilities

“…всего зарегистрированы 122 нежелательные реакции у 48,6% детей, частота была сходной для балоксавира и осельтамивира (46,1% против 53,4% соответственно). Наиболее частыми в обеих группах были желудочно-кишечные явления (рвота/диарея): 10,4% в группе балоксавира и 17,2% в группе осельтамивира, серьезных НЯ не зарегистрировано [55]. анализ вирусов гриппа, циркулировавших в сезон 2017-2018 гг., обнаружил, что до 0,08% вирусов являлись носителями аминокислотных замен, потенциально опосредующих резистентность к балоксавиру [56].…”