Baloxavir use appears safe in flu-infected infants

The use of baloxavir marboxil demonstrates good tolerability in children aged <1 year, with no new safety signals seen, according to a study.

Moreover, the clinical, virological, and safety outcomes of the study drug are consistent with established profiles in adults, adolescents, and children aged 1 to <12 years.

“The single-dose oral regimen of baloxavir has the potential to enhance accessibility of antiviral treatment for this population,” the researchers said.

In this phase III, multicentre, single-arm trial, the researchers examined patients <1 year of age who received a single dose of baloxavir (age ≥3 months: 2 mg/kg; <3 months 1 mg/kg). Safety was the primary endpoint, while pharmacokinetics and efficacy (time to alleviation of signs and symptoms, duration of fever and symptoms, antibiotic use, and cessation of viral shedding) were secondary.

Forty-eight of the 49 enrolled patients received baloxavir. Of these, 15 (median age 6 months) had positive centralized influenza reverse transcription polymerase chain reaction tests and comprised the intent-to-treat population. Among those with influenza infection, 79.2 percent were not vaccinated. [Pediatr Infec Dis J 2025;44:645-649]

Twenty-three patients reported experiencing a total of 51 adverse events (AEs), most of which were grade 1 or 2 in severity. Diarrhoea (16.7 percent) and vomiting (12.5 percent) were the most common AEs. Serious AEs occurred in two patients, but these were deemed unrelated to treatment.

In the intent-to-treat population, the median time to alleviation of signs and symptoms was 163.7 h (95 percent confidence interval [CI], 122.5–not estimable). Furthermore, the median fever duration was 23.1 h (95 percent CI, 22.3–44.6), and the median time to cessation of viral shedding was 24.5 h (95 percent CI, 24.2–68.6).

“These results expand on existing data from two Japanese open-label studies, which included a small number of patients <1 year old and demonstrated baloxavir to be well tolerated with a rapid reduction in viral load associated with symptom alleviation,” the researchers said. [Pediatr Infect Dis J 2020;39:706-712; J Infect Chemother 2021;27:1223-1229]

Susceptibility

All antiviral therapies for influenza infection exert selective pressure on viruses. This results in the emergence of variants with reduced susceptibility. [Clin Microbiol Rev 2021;34:e00224-e00220]

In the current study, patients <1 year of age had a resistance rate (15.4 percent) no greater than that observed previously in patients aged ≥1 years. However, only a small number of patients were included in this study and were eligible for genotyping. [Pediatr Infect Dis J 2020;39:700-705]

One patient with influenza A/H1N1pdm09 infection was found to have a PA/I38T substitution, which has been observed in previous studies involving children aged 1 to <12 years. Such substitution may result in reduced susceptibility to baloxavir. [Sci Rep 2018;8:9633]

“Whilst the patient with a PA/I38T substitution experienced a viral rebound on day 6, viral rebound was also recorded in two other patients without resistance,” the researchers said. “Therefore, in this small group of patients eligible for genotyping, resistance did not result in poorer clinical outcomes compared with the intent-to-treat population.”

“Baloxavir is a cap-dependent endonuclease inhibitor that inhibits viral replication at an early stage,” according to the researchers. “The safety and efficacy of single-dose baloxavir for treatment of influenza has been demonstrated in adults, adolescents, and children.” [Lancet 2022;400:693-706; N Engl J Med 2018;379:913-923; Lancet Infect Dis 2020;20:1204-1214]