Baloxavir's Place in the Treatment of Flu

Paul G. Auwaerter, MD


February 01, 2019

Hello. This is Paul Auwaerter, speaking for Medscape Infectious Diseases and from the Johns Hopkins Division of Infectious Diseases. What has impressed me about influenza is the terrible season we had last year, especially from the A(H3N2) seasonal influenza virus that the CDC estimated caused 80,000 deaths and the highest ever known confirmed number of pediatric deaths: 185.[1] This caused many of us to leverage that information into a message to make sure that our patients get immunized, which we know will help decrease the chances of having severe influenza or of having a terrible outcome such as death.

A number of things are new this year, but I'd like to focus on a new drug in the anti-influenza, antiviral armamentarium: baloxavir. Many of us are aware of oseltamivir, a drug that's been on the market for some years. A neuraminidase inhibitor that works differently from an antibiotic, it pairs the release of influenza from infected cells rather late in the viral life cycle, when it's budding. Oseltamivir is best if used early. There has been controversy about efficacy in some quarters, such as patients who are ill with an influenza-like illness. The CDC has advised using the drug for anyone who is hospitalized or at risk for serious illness, regardless of the timing of the infection. We know that the drug works best if taken very early (within the first 48 hours), but the data are mixed about whether it's helpful in ill patients later—on days 3, 4, or 5, for example.[2]

Oseltamivir is available only as an oral drug. Peramivir, which is available as a one-time intravenous dose, is occasionally used in very ill patients who are unable to take oseltamivir. Zanamivir gets precious little use as an inhaled powder because who wants to take a powder when having a respiratory illness?

Now we have baloxavir. This is a new oral medication with a very long half-life, of nearly 80 hours, so it's given as a single dose. This drug works differently from oseltamivir; it inhibits the acidic polymerase endonuclease, so it interferes with viral replication much earlier in the viral life cycle.

Hayden and colleagues[3] in the New England Journal of Medicine earlier last year published the results of a study in which they compared baloxavir with placebo and with oseltamivir. The drugs were taken within 48 hours of the onset of symptoms. Like oseltamivir, baloxavir worked reasonably well. It lessened fever by a day; patients felt better 1 day earlier. There was a rather marked reduction in viral shedding with baloxavir—much better than what was seen with oseltamivir, probably because baloxavir worked earlier in the viral life cycle. Some unpublished data presented at ID Week by Ison and colleagues[4] in high-risk adults also showed that baloxavir seemed to work by lessening symptoms by about a day and that it reduced viral shedding when compared with oseltamivir.

Baloxavir appeared to have a favorable side-effect profile compared with placebo. Side effects with baloxavir were less than with placebo and also less than with oseltamivir. In the Ison study, at least in the higher-risk patients, baloxavir appeared to decrease the rate of influenza complications and also reduced antibiotic use in this population.

Somewhat worrisome in the Hayden paper was that 2.2%-9.7% of viral isolates taken during this study showed that after administration of the drug, there was reduced sensitivity to the baloxavir compound. The meaning of this is not yet clear, but with oseltamivir we have seen very little resistance to date despite extensive use worldwide, especially in some countries with very high utilization, such as Japan. This poses some concerns that we need to follow over time.

Where does baloxavir fit? If a patient can take baloxavir as a one-time dose instead of taking it twice daily for 5 days (like oseltamivir), that's an advantage. Obviously baloxavir is a branded drug, so its higher expense must be taken into consideration. One of the more interesting questions is whether the reduced viral shedding associated with baloxavir will be of benefit, because perhaps fewer people will become infected in households or hospitals. Perhaps with additional study, benefits will be seen even in hospitalized patients because baloxavir works earlier in the viral life cycle.

So we have to stay tuned; we have to keep watch on the development of viral resistance. But baloxavir is yet another drug against influenza, which remains for many—both in the medical community and in the public—an underappreciated threat to our patients' health.

Thanks very much for listening.


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