Newly published findings of global drug trial show promise for preventing avian flu transmission

One dose of the antiviral baloxavir marboxil lowers the chance of transmitting the influenza virus to family members by about 30%, according to research in the New England Journal of Medicine.

In the study, a Phase III global trial of baloxavir marboxil (brand name Xofluza) led by University of Michigan epidemiologist Arnold Monto, researchers found that the drug significantly slowed the viral shedding that infects close contacts.

Dubbed the CENTERSTONE trial, the study involved 1,457 influenza positive patients ages 5-64 and 2,681 household contacts. The patients were randomly given either baloxavir or a placebo, and their contacts were followed to detect influenza transmission.

“There’s always been a question, could antivirals, which are known to shorten duration of influenza when used early in treatment, also prevent the spread of influenza,” said Monto, a longtime vaccine and respiratory contagions adviser to the Centers for Disease Control and Prevention and the Federal Drug Administration.

“We have had drugs which treat influenza in use for many years, but it has been unclear whether there was any reduction in transmission from the sick person. It also was not clear whether this was because no study was designed specifically to look for reduction in spread, or if no spread was taking place.

“Our study was designed to directly evaluate whether this meant we could finally establish that transmission could be reduced, and we were finally able to show that it was.”

Co-author Adam Lauring, chief of the Division of Infectious Diseases at the U-M Medical School, said the findings indicate great potential for lowering flu incidence.

“This was a really exciting study to work on,” said Lauring, professor of internal medicine and microbiology and immunology. “It highlights how we could potentially use an antiviral to help not just our patients but also households and larger communities by preventing influenza transmission. It could change how we approach future influenza outbreaks.”

Because other flu antivirals require a daily dose for five days and baloxavir is a single dose, it may mean greater use of treatment “since it means not only protecting oneself from complications but protecting others,” said Monto, professor emeritus of epidemiology and global public health at the U-M School of Public Health and co-director of the Michigan Center for Respiratory Virus and Research and Response.

“These findings extend the rationale for treating influenza patients with the antiviral. It’s a twofer: shortening the duration of the illness, which can also prevent complications leading to hospitalizations or deaths, while also reducing transmission.”

An antiviral that reduces viral shedding also brings promise for fighting the spread of avian flu, Monto said. While it has not been studied for avian influenza either in birds or dairy cattle, researchers have learned from laboratory studies that baloxavir prevents the replication of these kinds of influenza, as well.

In addition to funding from the trial sponsor and manufacturer Roche, the research was also funded by the Center for the Biomedical Advanced Research and Development Authority, part of the Department of Health and Human Services.