In the Journals: A New Class of Drugs to Treat Influenza

Two classes of drugs are available to treat influenza.

One class is the neuraminidase inhibitors (i.e., oseltamivir and zanamivir). These drugs work by inhibiting influenza virus’s neuraminidase: an enzyme located on the surface of the virus that allows it to leave the cell so that it can infect other cells.

The other class of drugs to treat influenza virus is the M2 (matrix 2) ion-channel inhibitors (i.e., amantadine and rimantadine). These drugs don’t allow the virus, once it has already entered the cell, to release its viral genome into the cell. Or, said another way, these drugs don’t allow the virus to uncoat.

Unfortunately, circulating influenza viruses are now largely resistant to amantadine and rimantadine and emergence of oseltamivir-resistant strains began during the 2008-2009 influenza season.          

Now a new class of drugs has entered the field. These drugs prevent influenza virus from reproducing its genome by working at the level of the viral polymerase (so-called transcriptional inhibitors). One such drug is called baloxavir marboxil.

Recently, baloxavir was tested in a large, prospective, placebo- and oseltamivir-controlled trial in adults with acute uncomplicated influenza (Hayden FG, Sugaya N, Hirotsu N, et. al. “Baloxavir Marboxil for Uncomplicated Influenza in Adults.” N Engl J Med. 2018 Sept 6;379(10): 913-23. DOI:10.1056/NEJMoa1716197). The trial, which included 1,024 patients, found that the time to alleviation of symptoms was 53.5 hours in the baloxavir group, 53.8 hours in the oseltamivir group, and 80.2 hours in the placebo group (p<0.001). Baloxavir was, however, associated with a greater reduction in viral load one day after the initiation of treatment than either the placebo or oseltamivir groups (p<0.001). The safety profiles were the same for the baloxavir, oseltamivir and placebo groups.

The authors concluded, “Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing viral load one day after initiation of the trial.”