Thursday, June 28, 2018

A flu drug — shown to reduce the duration of symptoms — could upend treatment in U.S.


JUNE 27, 2018
Next winter, there may be a new drug for people who contract influenza — one that appears to be able to shut down infection quickly and, unlike anything else on the market, can be taken as a single dose.
The Food and Drug Administration on Tuesday said that it would give the drug, baloxavir marboxil, a priority review, and approval has the potential to upend the way influenza is treated.
Baloxavir marboxil has already been licensed in Japan, where it is sold by Shionogi & Co. under the brand name Xofluza. Roche bought most of the global rights to the drugs — Shionogi retains the rights in Japan and Taiwan — and Genentech, a Roche company, is developing the drug for the U.S. market.
GENENTECH 
The FDA has told Genentech that it will issue a decision on baloxavir marboxil within six months — in other words, before Christmas.
The drug has been shown to reduce the duration of flu symptoms by a little more than a day — most uncomplicated flu infections only last a few days — and reduce the duration of fever by nearly a day. It also substantially cut the length of time people sick with influenza were coughing and sneezing out viruses — a potential benefit for the people around those sick individuals.
Here’s what you need to know about this drug.
Why the buzz
A single-dose drug that is potent and fast-acting is significant.
Any time you can make a drug easier to take, the chances that people will actually take it — and take it properly — go up. Public health authorities actually think flu drugs are underutilized, so a drug that works well and has more appeal to doctors and patients would be an advance.
The other flu drug people might know about, Tamiflu, is given as two pills a day for five days.
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Secondly, this drug works differently from all the other — and there aren’t that many other — flu drugs on the market. It is an endonuclease inhibitor; this is the first new class of influenza drugs to hit the market in over two decades.
There are only two other classes of flu drugs, neuraminidase inhibitors (drugs like Tamiflu, Relenza, Rapivab) and the adamantane drugs (amantadine and rimantadine). The latter class is not recommended for use because flu viruses quickly develop resistance to them.
New drug classes are always a welcome development because they provide a hedge if flu viruses develop resistance to existing drugs. “Just relying on essentially one class of drug for something that can have the public health impact that influenza can have is crazy,” said Richard Webby, head of the World Health Organization’s influenza collaborating center at St. Jude Children’s Research Hospital in Memphis. “So I think the more compounds we can have, the better.”
Another class of flu drugs also opens up the possibility of using drugs in combination to reduce the risk that viruses will develop resistance to the drugs, said Webby, who has studied another experimental drug in this class but is not involved in bringing baloxavir marboxil to market.
How it works
The drug interferes with a key step in the flu infection process. Flu viruses invade the cells in the human respiratory tract and use those cells as mini factories to pump out swarms of copies of themselves that then break out of those cells to infect others.
Endonuclease inhibitors stop that copying process.
Who it will likely be licensed for
Mark Eisner, Genentech’s vice president of product development for immunology, infectious diseases, and ophthalmology, said the clinical trial used to prove the drug worked enrolled subjects 12 years of age and older. So it’s likely if the FDA approves the drug, it will be approved for the same patient population.
Additional studies will be done to test the drug’s safety and effectiveness in younger children. Others will test to see if the drug benefits people who are hospitalized with severe influenza infections.
When it will hit the market
If the FDA approves baloxavir marboxil, will it be available next flu season? Maybe.
“We are working very hard to make it available as soon as possible after approval. And we will work with FDA to do everything we can to expedite [availability],” Eisner said.
The big unknown
The price set for this drug will be crucial. How much are people willing to spend to cut a day or so off of a bout of flu?
Genentech said it’s too early to comment on what the cost of the drug might be. In Japan, the drug sells for the equivalent of about $43.50.
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A related unknown
Tamiflu and the other drugs in its class never got the market acceptance in the U.S. that their manufacturers hoped and public health authorities expected them to get.
The reason: There has been a perception that the benefits — a little less time in bed — don’t justify trying to get a doctor’s appointment, get to the doctor’s office, and then find a pharmacy with the drug in stock. Many doctors also are underwhelmed by the drugs, and aren’t inclined to prescribe them.
Then there is the issue of the treatment window. Neuraminidase inhibitors work best if treatment starts within 48 hours of symptom onset. After that, in cases of uncomplicated flu, you’re into the realm of diminishing returns given that most patients’ symptoms will begin to dissipate on their own.
Baloxavir marboxil also needs to be taken within that 48-hour window — or at least that’s what is known about the drug now, Eisner said.
The question for the new drug will be: Does the prospect of a fast-acting, one-dose treatment override skepticism over flu drugs? Webby said it’s possible the “one-and-done” nature of the drug could increase usage.
Correction: An earlier version of this story misspelled the drug name baloxavir marboxil.

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