Demand, Cost for Avian-Flu Drug Could Leave Neediest With Least
By GAUTAM NAIK in Basel, Switzerland, and JAMES HOOKWAY in Bangkok, Thailand
Staff Reporters of THE WALL STREET JOURNAL
May 18, 2005; Page A1
Amid growing fears that an outbreak of avian flu could spark the next flu pandemic, wealth has become more of a factor than need in determining who will get an essential drug.
Richer countries facing little immediate avian-flu danger have moved in recent months to stockpile large amounts of the drug, called Tamiflu. The poorer Asian nations at the epicenter of the threat -- the key staging area for fighting the current outbreak and possibly forestalling the pandemic -- have only small-scale donations of the drug at present and scant resources for ordering large amounts.
Tamiflu has shown strong results in lab tests, has the backing of the World Health Organization, and was successfully used to quell a bird-flu outbreak in which Dutch farmers were infected in 2003. The drug is made by Roche Holding AG of Switzerland, which took a gamble in boosting production last year and may enjoy a substantial payoff.
But Roche is the only significant manufacturer; a rival flu drug made by Britain's GlaxoSmithKline PLC is harder to use because it must be inhaled, and it enjoys far lower sales. The Tamiflu production process takes 12 months, and existing stock of the drug wasn't large before Roche decided to increase production. Then last November, WHO officials urged countries to prepare for the threat of a pandemic partly by stocking up on Tamiflu. Roche won't disclose figures for how much of the drug it has in stock or will produce or has promised to deliver, but it's clear that demand has overtaken supply.
The bird-flu virus currently active in Asia is known as H5N1 and was first spotted in Hong Kong's poultry markets in 1997. It is unusual for its virulence -- it kills as many as 80% of those who catch it and has claimed more than 50 human lives -- and for its ability to jump to humans who come in close contact with an infected animal.
If the avian-flu virus infects a person already infected by a human-flu virus, the two bugs could then swap genes in such a manner that the new bug is able to easily jump from person to person. Almost no one would have immunity to such a new pandemic strain, WHO officials say. H5N1 has already been known to infect cats and tigers, and a few days ago, it was found in pigs, yet another mammal, on the Indonesian island of Java.
The 1918 flu pandemic killed between 20 million and 40 million people; the last one, in 1968, killed as many as four million people. The next is overdue, according to WHO officials, but it isn't known whether H5N1 will spark the next pandemic or if it will do so at all.
Scientists believe that if Tamiflu is quickly supplied at the site of an initial pandemic outbreak, it could help to contain the bug for as long as six months or even eliminate it. Six months is about what researchers would need to develop a vaccine based on the pandemic strain that emerges.
WHO officials recommend that all countries stockpile enough Tamiflu to cover 25% of their populations. But poorer Asian nations have lagged behind because of the drug's relatively high cost, about $3.90 a capsule.
Vietnam, the country hit hardest by avian flu and home to 84 million people, has only 2,000 treatments. Neighboring Cambodia, whose population is 14 million, has 300 Tamiflu treatments, most of it donated. Officials there say they need at least 15,000 treatment doses.
The dosage to treat flu consists of one capsule twice daily for five days. A preventive dosage, however, would be a capsule daily for as long as six weeks.
So far, much of the available Tamiflu production has been ordered -- or already received -- by developed countries.
In February, when one of Sweden's most eminent scientists, Hans Wigzell, suggested in a newspaper article that Swedes could prepare for a flu pandemic by buying antivirals, nervous Swedes rushed to pharmacies to stock up on the drugs. Critics on radio and television shows denounced Dr. Wigzell as a scaremonger. But soon after, the Swedish government announced it had ordered enough Tamiflu to cover half a million Swedes.
"If these antivirals can alleviate anxiety in ordinary families, what's the problem?" says Dr. Wigzell, a longstanding science adviser to the prime minister and a former president of Karolinska Institute, the country's premier medical university.
Norway, Canada, Australia, New Zealand, Finland and France have together ordered tens of millions of doses. The U.S. has so far requested 2.3 million treatments and could order more.
The U.K. has ordered $385 million of the drug to cover a quarter of its 60 million citizens. In February, London's mayor, Ken Livingstone, announced that he had separately ordered enough Tamiflu to protect 100,000 of the city's police, firemen and transport workers. WHO has an emergency "mobile stockpile" of 120,000 Tamiflu doses, but some health experts say the agency needs far more.
Tamiflu, to be effective, must be given within 48 hours after a patient starts to feel ill. Since flu symptoms resemble those of other ailments, including the common cold, many infected patients don't seek medical assistance until it is too late. Some studies also suggest that certain strains of the flu virus are resistant to Tamiflu.
Ensuring that Tamiflu gets to the front lines of an outbreak is so crucial to containing it that some public-health officials recommend that richer nations donate part of whatever stocks of Tamiflu they accumulate to the countries most affected by avian flu.
"Now that we can do something about it, we shouldn't be sitting on our haunches," said John Oxford, a British virologist whose research showed that Tamiflu was effective against the avian-flu strain. He suggests that wealthier countries set aside 10% or so of their Tamiflu stocks for use in Asian countries.
Sue Atkinson, director of public health for London, says the idea of donating Tamiflu to Asian countries didn't come up during the discussions that led to the city's order for Tamiflu. Health experts in Sweden say their first duty is to protect Swedes instead of trying to temporarily contain a pandemic virus in Asia.
"It would unfortunately have to be this chauvinistic attitude," said Dr. Wigzell, the Swedish scientist. "It might sound cruel, but it makes sense."
Dr. Sorasak Lachindarat of Queen Sirikit National Institute of Child Health in Bangkok, who treated several patients with bird flu last year, says it is understandable that Western governments and some in Asia are buying up Tamiflu "like weapons." But if bird flu doesn't spread to rich countries, he says, their Tamiflu stockpiles may expire before anyone in the world can use them.
Simply making more Tamiflu in the short run isn't a viable option. With a production cycle that lasts 12 months, Tamiflu is a difficult and expensive drug to manufacture.
Roche has already taken unusual steps to try and increase the drug's availability. For instance, it adopted what it calls a "bucket chemistry approach," offering Tamiflu's active ingredient, a white powder known as oseltamavir, in 15-pound barrels and at half the price of the capsule form. The powder can be dissolved in water and consumed. Tests have shown that this form confers the same protection as the capsule and can be stored longer. A small portion of the bucket form has been ordered.
The dearth of Tamiflu in Asia marks the second time in two years there has been a shortfall in a key flu treatment. Last year, Chiron Corp. of the U.S. failed to deliver half of the U.S.'s flu vaccine because of manufacturing problems at a plant in Liverpool, England.
Unlike Chiron, Roche hasn't encountered any manufacturing problems with Tamiflu. In fact, it took a gamble and increased production when there was little demand for the drug. The number of companies making flu treatments has declined markedly in recent years because the treatments are expensive and complex to make and typically carry low profit margins.
Roche launched Tamiflu in 1999 as a treatment for seasonal flu, but annual revenue was modest. "It was poor value for money compared to being vaccinated," says Duncan Moore, analyst at Morgan Stanley in London. Last year, Tamiflu sales fell 24% to 330 million Swiss francs ($270 million) from 431 million francs in 2003, partly because of a mild flu season.
But in early 2004, amid emerging concern over avian flu, senior executives of Roche held a meeting in Basel to discuss whether it made sense to boost Tamiflu production even though there were no stockpile orders from governments. Bill Burns, head of Roche's drug division, decided to take a chance and ordered Tamiflu production to be doubled in 2004.
"The risk was that nobody out there wanted it," Mr. Burns says. "But it was clear to me that this is what we had to do."
The gamble paid off. If countries continue to stock up on Tamiflu according to the WHO's recommendations, Roche could reap as much as $3 billion in Tamiflu sales over the next two years, analysts at Morgan Stanley estimate. A recent tour of a Roche warehouse in Basel revealed about 700 green barrels of bucket-form Tamiflu powder waiting to be delivered abroad. Roche is also building a new Tamiflu manufacturing plant in the U.S., and the company plans to again double production of the drug this year.
"Past pandemics have typically hit world populations like a flash flood," notes Klaus Stohr, head of the WHO's flu program, in a recent article in the New England Journal of Medicine. By comparison, the emergence of H5N1 "is an unprecedented warning and has given the world more time to prepare than anyone might have expected."
He adds: "We need to put up safeguards while the storm is still gathering." |
