Roche Raises Output of Bird Flu Drug

These days, in Hong Kong, it's still possible to walk into a drugstore, hand over HK$200 (U.S. $25) to a clerk, and walk out with a box of 10 capsules of Tamiflu, the antiviral drug that shows promise in treating humans for the deadly avian flu. Local pharmacists say they face no particular difficulty in stocking Tamiflu (oseltamivir phosphate) and that public demand for it is not particularly strong. F. Hoffmann-La Roche, which makes the drug, says 10 capsules are enough to treat a bout of the flu.

But the drug will become harder to find if the flu strain now spreading in Asian bird populations mutates into a form that can spread rapidly among people and precipitates a bird flu pandemic. In the spring of 2003, when Hong Kong was tensely fighting off SARS (severe acute respiratory syndrome), a teenager posted on a website the fake news that Hong Kong had been declared a diseased harbor, something that would disrupt food shipments to the territory. This caused thousands of people to rush to supermarkets in the middle of the afternoon to stock up on essentials like staple foods and bottled water.

Roche is well aware of the likelihood that demand for Tamiflu would surge during a bird flu pandemic, not just in Hong Kong, but worldwide. The company insists there is no shortage at present. But for the past few years, it has been advising health administrations around the world to stock up on this neuraminidase inhibitor. "We have been very clear that if a pandemic were to start tomorrow, the demand would be so steep that we could not guarantee that a government could get its supply," David Reddy, head of Roche's pandemic task force, says.

Few governments have been heeding Roche's advice. The company says it takes about 12 months to produce Tamiflu, which is one of the company's more complex drugs. At present, the company requires 12–18 months to supply new orders. A few countries, including Norway, Ireland, the U.K., and New Zealand, have enough capsules to treat up to 40% of their populations. Fewer than 20 countries, however, have stocked up on Tamiflu, many have not placed orders, and the supply of the drug worldwide is enough to treat only about 40 million people.

To help overcome this apparent lack of preparedness, Roche says it will donate 30 million capsules of Tamiflu-enough for 3 million treatments-to the World Health Organization. The capsules would allow WHO to attempt to contain a pandemic in its early stages, regardless of whether the stricken area has its own stock of the drug.

Some health experts believe governments should consider resorting to compulsory licensing-that is, ignoring Roche's ownership of the drug to make up for the Swiss company's inability to cope with demand during a pandemic (C&EN, April 4, page 47). But Yusuf K. Hamied, chairman and managing director of Indian drug company Cipla, warns it would take about three years for his company, or any other firm, to be able to start producing Tamiflu because of the drug's complexity. And he adds that he cannot begin in earnest to plan to produce Tamiflu until he has some official assurance that he will not be accused of breaking the law for doing so.

"This is what I have been warning about," he says, referring to his opinion that current drug patent laws do not serve the public interest. The leading supplier of drugs to the Indian market, Cipla is famously controversial for launching a generic version of an AIDS treatment consisting of three drugs that still enjoy patent protection in most countries. Until this year, the Indian government did not recognize patents on pharmaceuticals.

It's pointless to look at ways for outsiders to produce Tamiflu, Roche's Reddy says. He notes that Roche can meet demand expectations faster than anyone else because it is familiar with the challenging production process. To meet current orders, Roche has quadrupled production capacity since 2003, and it plans to double capacity again by next summer. Roche produces Tamiflu at three sites in Europe and one in the U.S.

Gilead Sciences, the U.S. company that invented Tamiflu and licensed the drug to Roche in 1996, is unimpressed by the Swiss firm's efforts surrounding the drug. In June, Gilead sent to Roche a request to end the licensing agreement and recover its rights to the drug. Gilead claimed in a press release that "Roche has not adequately demonstrated the requisite commitment to Tamiflu since its launch in the U.S. nearly six years ago, nor has it allocated the necessary resources to realize the potential of the product as a treatment and preventive for influenza." Reddy says Roche is "disappointed" with Gilead's action and promises that this development will in no way affect Roche's efforts to boost capacity.

Meanwhile, there are some doubts that Tamiflu will be able to maintain its status as the most effective tool to contain a flu pandemic. For one, it has not been tested conclusively against avian flu. In a paper published this month in Foreign Affairs, Laurie Garrett, senior fellow for global health at the Council on Foreign Relations (a nonpartisan membership organization for foreign policy study), notes that the best way to treat the avian flu virus is as yet unknown. The World Health Organization recommends stockpiling Tamiflu mostly because few other options are available, she writes.

A possible alternative to Tamiflu is Relenza (zanamivir), another neuraminidase inhibitor that GlaxoSmithKline produces under license from Biota, an Australian antiviral drug discovery company. Like Gilead, which licensed Tamiflu to Roche, Biota is not happy with the way the larger company is promoting the drug. Biota has taken the extra step of suing GSK for alleged failure to effectively promote Relenza. Earlier this month, however, the German government placed an order for 1.7 million packs of Relenza, the biggest ever order for the drug. This follows the publication of a study this month in the British medical journal Lancet recommending Relenza as superior to Tamiflu in terms of effectiveness and side effects. Hong Kong, which is likely to be one of the first areas to be hit if there is a flu pandemic, stocks both drugs.

But Hong Kong has little faith in an avian flu vaccine that may become available soon, a spokeswoman for the Department of Health says. France's Sanofi Pasteur has begun testing a new vaccine that promises to immunize patients against bird flu. But even if the vaccine proves effective and Pasteur licenses it to anyone who asks, there may not be enough vaccine production capacity worldwide to inoculate more than a small fraction of the world population initially. Michael T. Osterholm, director of the Center for Infectious Disease Research & Policy at the University of Minnesota, Twin Cities, warned this month in another paper in Foreign Affairs that the world may have to go through one to three years of an avian flu pandemic before a vaccine becomes widely available.

Despite the emergence of these alternatives to Tamiflu, medical authorities worldwide are still betting on the Roche drug as their best weapon in the fight against an avian flu pandemic. If such a pandemic does break out, an event that seems ever more probable, Tamiflu will become a very precious substance if it proves its effectiveness against the new influenza strain.