Flu has been on a vicious march this winter, evading vaccines, overwhelming hospitals and prompting school closures from California to Hong Kong in its wake. But relief in the form of new drugs is on the way.
Almost two decades after Roche Holding AG’s Tamiflu first reached pharmacy shelves, researchers around the world are pushing ahead with a raft of new options. None will arrive in time to help sufferers this winter, but the most advanced — developed by Roche and Shionogi & Co. — could be on the market in Japan within months and available in the U.S. and Europe next winter.
“For several decades now, we have not sought to develop the tools we need to fight the flu,” said Olga Jonas, a senior fellow at the Harvard Global Health Institute in Boston and former World Bank economist. “The tax we pay for this folly is as inexorable as it is enormous.”
Tamiflu, which generated more than $3 billion in sales when swine flu sparked a global contagion in 2009, reduces the duration of illness by only up to a day if it’s taken within the first 48 hours of the onset of symptoms. What’s more, some seasonal strains have developed mutations that decrease its potency, spurring calls for alternatives.“It’s very important to have more options, as you can tell from this flu season,” said Daniel O’Day, head of Roche’s pharma unit, in an interview in Basel, Switzerland on Feb. 1.
Tamiflu, also known by its chemical name oseltamivir, works by blocking a protein on the surface of flu viruses called neuraminidase that enables newly made germs to escape from an infected cell and spread. GlaxoSmithKline Plc’s Relenza, BioCryst Pharmaceuticals Inc.’s Rapivab and Daiichi Sankyo Co.’s Inavir operate in a similar way.
“We really do need another effective antiviral with an alternative biological mechanism,” said Benjamin Cowling, professor and head of epidemiology and biostatistics at the University of Hong Kong.
Baloxavir, the flu drug discovered by Osaka, Japan-based Shionogi, received preliminary approval in Japan last week. Co-developer Roche aims to file for regulatory review in the U.S. and Europe later this year, according to O’Day.
The medicine works by inhibiting an enzyme that the virus needs to replicate inside a host cell and requires a single dose, unlike Tamiflu, which is usually taken twice a day for five days.
“The advantage is that it’s one pill once, versus a course of therapy, so particularly for pandemic planning, this could be an advantage,” O’Day said. “You don’t have the potential resistance that comes with not completing your course of therapy.”
Johnson & Johnson’s Janssen unit could be next to market with a therapy called pimodivir, which should enter a late-stage study early this year. The experimental medicine received fast-track designation from the U.S. Food and Drug Administration in March due to its potential to address an unmet medical need. Discovered by Vertex Pharmaceuticals Inc., the drug targets part of a gene present in the majority of seasonal flu viruses, blocking them from making copies of their genetic material.
Another potential therapy in the most advanced stage of testing is nitazoxanide, which wasn’t developed for influenza. The drug is the only licensed treatment for a type of waterborne parasitic infection. In flu viruses, it prevents mature virus particles from leaving host cells.
J&J is also pressing ahead with the development of a universal flu vaccine. A shot that works against multiple strains of the virus is a holy grail for the medical field because it could eliminate the need to formulate a new vaccine every year.
There’s another approach that is years away because it hasn’t been tested in humans, but which Lorena Brown, a professor of microbiology and immunology at the University of Melbourne, says may have the potential to transform the field.
Melbourne scientist Wen-Yang Wu, who helped discover Relenza, is developing a novel way of preventing flu viruses from infecting respiratory cells. It works by reshaping the hemagglutinin, another protein on the surface of the virus, by creating a low pH environment that mimics the change that occurs after a virus invades a host cell, he said.
In the presence of the drug, the virus prematurely and irreversibly changes the conformation of hemagglutinin, rendering it unable to bind and enter the cell, according to Wu. In animal studies, a single dose has been shown to provide monthlong protection against flu, and a single dose 72 hours after infection has been shown to successfully treat the disease.
“This is a totally new and very clever concept of how we think about making antivirals,” said Brown, whose lab undertook some of the testing. “If it works as well in humans as our animal studies show, it will dramatically enhance our options.”
Aus Bio Ltd., which is developing the medicine, may be able to begin trials in humans in 12 to 18 months depending on the outcome of talks with potential partners, said Peter Jenkins, an executive director.
Besides so-called small-molecule drugs, at least five different antibody-based therapies are being evaluated in clinical trials to treat severe flu cases, according to Aeron Hurt, a senior research scientist with the World Health Organization’s Collaborating Center for Reference and Research on Influenza in Melbourne. Most rely on features of the human immune system to neutralize proteins on the surface of flu viruses.