Baloxavir for Kids? What We Know About This New Flu Antiviral

Andrew T. Pavia, MD


February 22, 2019

A New (and Different) Flu Antiviral Debuts

Existing flu antivirals have limitations. While they can be lifesaving in hospitalized patients, they reduce duration of illness by only a little over a day. Their antiviral potency is modest. That is why the introduction of baloxavir was highly anticipated.

For the first time in two decades, we have an antiviral for flu with a novel mechanism of action and the convenience of a single dose. But for now, at least, not everyone can benefit from the drug.

Baloxavir is approved only for the treatment of uncomplicated influenza in patients aged 12 years and older. In Japan, baloxavir can be given to kids younger than 12 years who weigh more than 10 kg; but in the United States and Europe, regardless of weight, young kids are missing out.

When might this change? And are there circumstances in which we should consider off-label use in children?

What We Know to Date

An inhibitor of the influenza cap-dependent endonuclease, baloxavir is active against influenza A (including many avian strains) and influenza B.

In a phase 3 trial[1] comparing a single dose of baloxavir with oseltamivir twice daily for 5 days and placebo in otherwise healthy adults and adolescents, baloxavir shortened the median time to alleviation of symptoms by 26 hours compared with placebo, similar to oseltamivir. Of note, the median duration of shedding of infectious virus was only 1 day for baloxavir compared with 3 days for oseltamivir.[1]

Healthy adults and adolescents, however, are not the groups most likely to benefit from antiviral therapy. The real need for an effective antiviral drug is for children and teens at high risk for influenza complications. Guidance from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the Infectious Diseases Society of America is similar: While antivirals can be considered for healthy outpatients in the first 48 hours, they are recommended for those at risk for complications of influenza (including children under 5 years of age, especially those under 2 years) and for hospitalized patients. And in these groups, data for baloxavir are limited.

A second randomized trial[2] with a similar treatment regimen was presented at IDWeek 2018 but has not yet been published. This trial enrolled high-risk outpatients aged 12 years and older with fever and influenza symptoms who had at least one risk factor for influenza complications. Among patients with influenza A, baloxavir reduced the median time to symptom resolution by 29 hours compared with placebo, but this was not statistically superior to oseltamivir (21 hours), despite substantially more rapid clearance of the virus. Among patients with influenza B, symptoms resolved 26 hours earlier with baloxavir compared with placebo (74.6 vs 100.6 hours; P = .014). Baloxavir was also superior to oseltamivir for patients with influenza B (74.6 vs 101.6 hours; P = .025), and the drug reduced both influenza complications and antibiotic prescriptions.

Resistance is a potential concern. In both studies, viral escape mutants with reduced susceptibility were detected in up to 10% of patients treated with baloxavir. This may be more important in critically ill and immunocompromised patients with influenza, in whom antiviral resistance emerges more readily to neuraminidase inhibitors (NAIs). An appealing strategy is to combine two drugs with different mechanisms of action, a method that has succeeded in the treatment of HIV and hepatitis C. In vitro, this seems to make sense because baloxavir and NAIs are synergistic. In a lethal mouse model, the combination of baloxavir and oseltamivir markedly improves survival. Clinical data are not yet available, although a clinical trial of baloxavir/NAI combination therapy compared with monotherapy is underway. Another clinical trial in children 1-12 years of age is enrolling, and a pharmacokinetic study in children younger than 1 year of age should begin soon.

Until we have better data, I see no compelling reason to use baloxavir over oseltamivir for younger children with mild to moderate influenza.

Is Off-Label Baloxavir Use in Children Justified?

What, then, should we do for children while awaiting results of these critical studies? Until we have better pharmacokinetic and resistance data for children, I see no compelling reason to use baloxavir over oseltamivir for younger children with mild to moderate flu, or for patients hospitalized with uncomplicated disease. However, for the most gravely ill patients and for severely immunocompromised patients (such as transplant recipients), it is worth considering adding baloxavir to an NAI. This should be done in consultation with an infectious disease expert, and perhaps use the multiple-dose regimens being evaluated in clinical trials.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.