From: Reuters
Published May 14, 2008 02:06 PM

Bird flu pandemic seen needing multiple drugs

By Ben Hirschler

LONDON (Reuters) - Governments need to stockpile different sorts of flu drugs -- not just Roche Holding AG's Tamiflu -- to counter the danger of resistance in a pandemic triggered by bird flu, British experts said on Wednesday.

The warning could boost demand for GlaxoSmithKline Plc's inhaled medicine Relenza, which has been largely overlooked in favor of Roche's more convenient pill.

Scientists analyzing the structure of a key flu virus protein found that both H5N1 and seasonal flu could develop resistance to Tamiflu, while still remaining highly susceptible to Relenza.

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"What this research shows is that stockpiling any one drug to prepare for a potential H5N1 pandemic is unlikely to provide adequate cover," said Steve Gamblin of the National Institute for Medical Research in London.

"In order not to be outflanked by the virus, it will be necessary to have stocks of both existing drugs."

There is a also "a huge imperative" to develop further drugs since the best way to treat patients in the long term is likely to be a three- or four-pronged approach, similar to the multi-drug cocktails used to fight HIV and AIDS, Gamblin said.

A new influenza drug, peramivir, is being developed by Biocryst Pharmaceuticals Inc but it must be injected and it has not performed well in clinical trials. Two older flu drugs are available but flu viruses have quickly developed resistance to them, although some experts believe they may be useful in cocktails with newer drugs.

Both flu viruses and HIV have a high rate of mutation, which allows them to adapt to the treatments devised to tackle them.

To date, H5N1 remains mainly a virus affecting birds, although it has killed more than 200 people since 2003. But scientists say it is the most likely source of the next deadly flu pandemic in humans, since it may soon mutate into a form transmitted easily from person to person.

Tamiflu, known generically as oseltamivir, and Relenza, or zanamivir, target the viral protein neuraminidase, which helps release newly made viruses so that they can spread infection.

Using a technique called X-ray crystallography, Gamblin and colleagues examined the exact mutation in protein structure that can make some flu virus resistant to Tamiflu and showed the different nature of Relenza meant it was still effective.

Their results were published in the journal Nature.

The main seasonal flu virus circulating this year in the United States and Canada as well as parts of Europe has shown higher resistance to Tamiflu. But cases of resistance remain relatively rare.

Tamiflu, which was originally developed by Gilead Sciences Inc, had sales of 1.9 billion Swiss francs ($1.8 billion) in 2007, making it a major profit driver for the Swiss group. Relenza, which Glaxo licensed from Australia's Biota Holdings Ltd, sold 262 million pounds ($510 million) last year.

(Editing by David Holmes)

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