Bird Flu: Science and Policy

[DewDiligence]

Big Pharma Disagree re Commercial
Potential of Pre-Pandemic Vaccine

http://online.wsj.com/asia

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By Nicholas Zamiska
02-15-07 1632ET

Drug makers have developed a vaccine for the bird-flu strain that scientists fear could mutate and spark a global pandemic. Now regulators and companies are weighing whether or not to make it widely available before any outbreak occurs.

Girding for the possibility of a large-scale outbreak among humans of a highly lethal form of avian influenza, scientists have been working on a vaccine that could conceivably save millions of lives. In the past few years, big pharmaceutical companies such as GlaxoSmithKline PLC and Sanofi-Aventis SA have made steady progress. Governments already are stockpiling supplies of a vaccine that appears to work.

So far, the plan seems to be to use a vaccine only if an outbreak occurs. The vaccine has yet to get an endorsement from any regulatory agency for prepandemic use. Still, potential demand for such prepandemic protection was flagged last year, when fears of a bird-flu pandemic sent people around the world rushing to buy up supplies of Roche Holding AG's antiviral drug Tamiflu, which can be used to treat the disease. An effective vaccine could be just as important as Tamiflu, if not more important, in saving a person from avian influenza.

"We have calls from people saying, 'Can I buy it? Can I buy it?'" says Alain Bernal, a spokesman for Sanofi Pasteur, the vaccine unit of Sanofi-Aventis of France.

Experts say it wouldn't make sense to cut corners on a normal regulatory process, given that the threat is a hypothetical one at this stage. They also point out that production capacity is needed to make vaccines for seasonal influenza, which poses a more immediate threat.

The European Union is weighing the pros and cons of a prepandemic vaccine, says Marie-Paule Kieny, director of the initiative for vaccine research at the World Health Organization, which on Thursday began a two-day meeting in Geneva with vaccine makers from around the world that are working on a bird-flu product.

Possible advantages, she says, include people being primed before a pandemic and needing only a booster dose should an outbreak occur. On the other hand, dangers include adverse effects and whether a vaccine against the current virus would even be effective against a mutated form of the virus.

At Sanofi, Mr. Bernal says making bird-flu vaccine for a potential threat would cut into the company's production capacity for vaccines for seasonal flu, which kills an estimated 250,000 to 500,000 people world-wide every year. By contrast, the H5N1 strain of bird flu, the one that worries health authorities most, has infected at least 273 people, killing 166 of them, mostly in Asia, since the virus re-emerged in late 2003, according to the WHO.

Mr. Bernal says global vaccine-production capacity for seasonal influenza already is limited to an estimated 350 million doses a year, of which Sanofi Pasteur produces about half. "The real public-health need today is for seasonal flu," he says. "You either produce [vaccines for] seasonal flu or H5N1."

As a result, he says, the H5N1 vaccine "is not a vaccine that we want to sell to the public. We don't have a marketing strategy for this product," Mr. Bernal says. A committee of outside advisers to the U.S. Food and Drug Administration is scheduled to meet Feb. 27 to make recommendations on the safety and effectiveness of Sanofi's H5N1 vaccine.

In addition, the current H5N1 vaccine seems to require a high dose to offer protection, making production issues worse, says Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, which has been working with vaccine makers on an antidote for a government stockpile. "It's not going to be something you're going to see on the shelf for sure," Dr. Fauci says. "It will likely be strictly controlled."

What's more, public-health officials warn that using a vaccine for an outbreak that might never materialize could carry more risks than rewards. Even approved new vaccines involve a certain amount of risk, especially if administered on a large scale, and there is a "wariness of using a vaccine that might not even be necessary," says David L. Heymann, the director-general's acting representative for avian influenza at the WHO.

Bird flu has waxed and waned in the public spotlight for three years now, but scientists take it seriously as a pandemic threat. Currently the H5N1 virus passes occasionally from birds to humans, killing more than half of the people it infects (although that fatality rate may be lower if cases are going undetected). If the virus mutates to a form that could pass readily among people, it could take a massive toll.

The current vaccines are based on strains of the H5N1 bird-flu virus from recent years; should the virus mutate, as it would need to in order to spread among humans, it isn't clear that the vaccine would fully protect people against it. Still, some experts think the current vaccine probably would protect against severe illness and death, even if the victim still got sick. Governments are proceeding on that assumption, and millions of doses have been produced.

GlaxoSmithKline received approval from European drug regulators in December for one of its H5N1 vaccines, but only for use in the event of a pandemic, according to Alice Hunt, a spokeswoman in London for the company. Last month, the British drug company submitted another application for an H5N1 vaccine that could be used in advance of a pandemic.

Ms. Hunt says it is far too early to consider marketing that vaccine to consumers, since the company has only just submitted its application to the European regulator and is planning on submitting it to the U.S. FDA as well.

CSL Ltd., an Australian pharmaceutical company, announced last month that it had produced a safe, effective vaccine against H5N1. Australia's drug watchdog will soon review the company's application. CSL has no plans to market a version of the vaccine for general use, according to Rachel David, the company's spokeswoman.

Medical-products maker Baxter International Inc., of Deerfield, Illinois, is testing its H5N1 vaccine and has signed a deal with the British government to produce two million doses for a stockpile. Whether Baxter will ever market the vaccine directly to consumers is an open question, according to Deborah Spak, a spokeswoman for the company. "We are still under clinical evaluation and years away from receiving the approvals needed for commercialization," she says, adding that the company hasn't built sales of a bird-flu vaccine to consumers into any of its financial projections.

Some companies do say they see commercial potential in the vaccine. In November, the Swiss drug giant Novartis AG submitted its H5N1 vaccine to the European Medicines Agency in London for approval, according to Eric Althoff, a spokesman for the vaccine unit of the Swiss company. Mr. Althoff says he expects a response on that application this year.

Novartis believes that if that vaccine is approved, there is a potential commercial market for a prepandemic vaccine that would be sold to individuals and not just governments, he says.
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