Experts warn that the antiviral drug Tamiflu alone is an imperfect defense against a possible pandemic.
By LISA GREENE, Times Staff Writer
Published October 31, 2005
If doctors' worst visions come true, and bird flu explodes around the world, experts say a drug called Tamiflu could save countless lives.
Scientists say it's the best hope for treating deadly bird flu, which kills as many as half of the people infected. The United States is spending millions to stockpile up to 20-million new doses. The company that makes it is besieged by orders and rushing to make more.
There's so much publicity about Tamiflu that many doctors worry that scared citizens will hoard it. Last week, the drug's maker, Hoffman-La Roche Inc., temporarily suspended Tamiflu shipments because of reports that some groups are doing exactly that.
But despite the frenzied rush to get more of the drug, Tamiflu is not a cure.
"We should not expect perfection, or we'll be disappointed," said Dr. William Schaffner, board member of the National Foundation for Infectious Diseases and chairman of preventive medicine at Vanderbilt University.
Even though the United States is pursuing new supplies of Tamiflu, federal officials worry that the antiviral drug is getting too much attention. A huge supply of Tamiflu will be needed to help contain a pandemic, but it's only one part of the puzzle, said Christina Pearson, spokeswoman for the U.S. Department of Health and Human Services.
"We don't know right now what the next pandemic strain will be," she said. "It's uncertain if it's going to be H5N1 (bird flu). It's uncertain whether Tamiflu, or other things - how effective they will be against that strain. Part of our strategy will be to stockpile antivirals. To put it bluntly, you don't want to put all your eggs in one basket."
Tamiflu is one of four antiviral drugs designed to treat the flu, which typically kills an average of 36,000 Americans each year. Scientists believe it is the best option to treat the strain of bird flu, known as H5N1, now circulating in Asia. The United States also is increasing its supplies of a second drug, Relenza.
Bird flu already has killed more than 60 people in Asia, generally because they came in contact with infected birds. This flu strain is especially deadly, and people have no immunity to it.
Flu viruses are notoriously unstable, and doctors fear that if bird flu mutates so that it can spread easily from person to person, it will spread around the world. Such a pandemic could kill anywhere from 2-million to 150-million people, doctors say.
The flu virus makes people sick by invading a human cell and hijacking its genetic material to produce more virus. New virus then bursts out of the human cell, killing it in the process, and goes out to find more cells where it can invade and multiply.
Tamiflu works by breaking that cycle. The virus can still get into the cell and make more virus. But an inhibitor in Tamiflu keeps the new virus from leaving.
That ability could save lives if a pandemic hits.
"It could make a substantial difference," said Dr. Frederick Hayden, a professor at the University of Virginia who has published several studies on antiviral drugs. "The estimates ... have suggested that you might be able to cut mortality roughly in half."
Those estimates come from smaller studies and may not compare to treating mass numbers of people. Still, scientists believe antiviral drugs hold so much promise that one national infectious disease group recommends the United States stockpile 67-million to 124-million doses of antiviral drugs.
"We're playing catchup right now," Hayden said. "I hope that the virus gives us time."
Tamiflu's effects aren't overwhelming. In clinical trials of Tamiflu, patients taking it felt better 30 percent sooner than patients who didn't - a difference that translates into 1.3 fewer days of illness.
"It's not a light switch, that three days after you take it, you're back to doing pushups and running," Schaffner said.
In other studies, the drug has been 92 percent effective in preventing flu.
Such studies are encouraging. How long Tamiflu's effectiveness would last is another question. Bird flu already shows resistance to two other, older flu drugs. In a pandemic, "it would only be a few short mutations away from being Tamiflu-resistant," said Dr. John Sinnott, director of the Florida Infectious Disease Institute at the University of South Florida.
That's a chief reason doctors are so worried about individuals stockpiling Tamiflu. At the first sign of a cough or sniffle, they may break out the pills - even though they most likely don't have flu.
"There will be some people who, on their own initiative, will take some, in inadequate doses," Schaffner said. "That's a prescription for resistant virus. So I really don't think personal stashes of Tamiflu are the best idea."
One of the biggest worries: Tamiflu is most effective if a person takes it within the first two days of showing symptoms. That's hard enough under normal circumstances, when people often delay visiting the doctor until they've been sick for several days. But trying to deliver massive doses of drugs in time makes many flu experts worry.
"Last year was a horrible mess with the distribution of the flu vaccine," Sinnott said. "Obviously the distribution system (for Tamiflu) would have to be refined."
Health officials need to plan for that two-day window now, Hayden said.
"I honestly don't think the conventional method of people coming to their primary-care (doctor) will work," he said. "All they'll do is bring their virus with them. We'll have to figure out how to get the drug to them."
HHS staffers are working on how best to distribute antiviral drugs quickly, Pearson said.
The short window for Tamiflu's impact, combined with the possibility that there won't be enough, sets the stage for ethical struggles.
"Who is more deserving: a young healthy person, with many years of life ahead? A person at great risk? Someone who's pregnant?" Sinnott asked. "It's very unclear."
During last year's flu vaccine shortage, those at greatest risk for severe illness got first priority: the very old, the very young, the sickly.
Bird flu could change that. This month, many scientists were shaken by the re-creation of the virus that caused the 1918 flu pandemic, revealing that it was a bird flu that jumped to humans. The 1918 flu killed more than 40-million people around the world, and it didn't behave like normal flu. Many who died were young, healthy adults - those ordinarily at least risk.
"If it's one like 1918 ... then we have to have health authorities make very hard decisions about who should get this," Hayden said.
His best answer: keep stockpiling so there's enough drug to go around.
Roche has been criticized for acting too slowly in the past to produce more of the drug, and, more recently, for refusing to license generic versions to other companies. An Indian drug company has said it plans to make a generic version.
A Roche spokesman did not return calls for comment, but pointed out via e-mail that the company doubled its manufacturing capacity in 2004 and will increase up to tenfold by mid 2006. This month, the company announced that it's ready to talk with other companies that could help make Tamiflu.
It is vital that the United States continue to pursue other ways to prevent or minimize the threat, Pearson said.
"It's worrisome when so much attention is focused on one specific element, such as Tamiflu," she said. "It would be wrong to use that as a measure of any nation's preparedness. Tamiflu is like a seat belt. It helps to minimize injury if you're in an accident, but it doesn't prevent the accident from happening in the first place. We've been working on a strategy that does many things."
Other key parts of federal pandemic planning include developing a bird flu vaccine and increasing capabilities to make such a vaccine quickly, increasing surveillance in hopes of spotting an outbreak quickly enough to contain it, and working more closely with other countries.
