# 4385
Five years ago we had four antiviral drugs that worked pretty well against nearly all of the influenza viruses in circulation. We had the old standbys of Amantadine and Rimantadine, which had been around nearly 50 years, along with the relatively new drugs Tamiflu and Relenza.
But by late 2005 it became apparent that the H3N2 seasonal flu virus was becoming resistant to the older class of drugs. The cause was suspected by many to stem from the illegal and indiscriminate use of Amantadine as an additive to chicken feed in China.
While still effective against the H1N1 seasonal virus, in January of 2006 the CDC recommended that drugs of the Amantadine class no longer be used against influenza. Tamiflu (oseltamivir) was the new `go to’ drug, with Relenza (zanamivir) as a backup.
With the prospects of a pandemic on the horizon, many nations invested heavily in Tamiflu, stockpiling hundreds of millions of capsules.
Then . . . in 2008, we began to see signs of resistance forming to Tamiflu as well. This time in seasonal H1N1. Within a year, nearly all seasonal H1N1 viruses were resistant.
While still effective against the H3N2 viruses, novel H1N1, and most of the avian strains there are concerns that the `life’ of Tamiflu may be limited. Victories against viruses and bacteria sometimes prove to be short-lived.
Therefore, new antivirals are a hot research field right now.
One of the brighter prospects undergoing testing is CS-8958, or laninamivir, being developed by Daiichi Sankyo Co Ltd.
PLoS Pathogens has a study revealing promising test results in its latest edition entitled:
Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses
Maki Kiso, Shuku Kubo, Makoto Ozawa, Quynh Mai Le, Chairul A. Nidom, Makoto Yamashita, Yoshihiro Kawaoka
At least two of the authors listed above should be familiar names to readers of this blog; Yoshihiro Kawaoka and C. A. Nidom.
A few choice excerpts from the abstract, followed by Maggie Fox’s story from Reuters.
ABSTRACT
CS-8958 functions as a long-acting NA inhibitor in vivo (mice) and is efficacious against seasonal influenza strains following a single intranasal dose. Here, we tested the efficacy of this compound against H5N1 influenza viruses, which have spread across several continents and caused epidemics with high morbidity and mortality.
We demonstrated that R-125489 interferes with the NA activity of H5N1 viruses, including oseltamivir-resistant and different clade strains. A single dose of CS-8958 (1,500 µg/kg) given to mice 2 h post-infection with H5N1 influenza viruses produced a higher survival rate than did continuous five-day administration of oseltamivir (50 mg/kg twice daily).
Virus titers in lungs and brain were substantially lower in infected mice treated with a single dose of CS-8958 than in those treated with the five-day course of oseltamivir. CS-8958 was also highly efficacious against highly pathogenic H5N1 influenza virus and oseltamivir-resistant variants.
These results stem from a mouse model, and one must always be mindful that what works in mice doesn’t always work in humans.
Still, the big news is that one dose of this inhaled antiviral works as well as a five day regimen of Tamiflu (in mice), and that it is effective against antiviral resistant strains of H5N1.
The manufacturer hopes to bring this new drug to market next year.
Maggie Fox picks up the story for us.
New inhaled drug protects from flu in single dose
By Maggie Fox, Health and Science Editor
WASHINGTON (Reuters) – A single dose of an experimental influenza drug saves more mice from H5N1 avian influenza than the preferred drug Tamiflu, researchers reported on Thursday, and can also protect against infection.
The tests of Daiichi Sankyo Co Ltd's CS 8958 or laninamivir show one inhaled dose worked better than Tamiflu to keep mice alive when infected with a normally deadly dose.
The report in the Public Library of Science Journal PLoS Pathogens covers one of the dozens of ongoing studies of a new batch of influenza drugs being developed by a variety of companies.
"Importantly, a single dose of CS-8958 conferred a more potent and long-lasting protective effect to mice against H5N1 influenza viruses than that of oseltamivir phosphate," Yoshihiro Kawaoka of the University of Wisconsin and colleagues wrote in their report.
