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Human bird-flu fatalities spur need for more effective drugs - extended

Doctors and health officials are preparing to experiment with new drugs in an effort to find better ways to treat lethal bird flu infections.

The WHO wants permission to use BioCryst Pharmaceuticals Inc.'s experimental peramivir antiviral to treat patients infected with the H5N1 avian influenza virus and other severe flu infections, said Frederick Hayden, a WHO medical officer. Injections of peramivir reach higher levels in patients' systems than oral drugs such as Roche Holding AG's Tamiflu, now the preferred drug for bird flu treatment, he said. About 60% of the people infected with avian flu in Asia, Africa and the Middle East have died. Stronger treatments are needed, especially if the bird virus mutates into a form that spreads easily in people, Hayden said. „The hope would be that in patients who present with particularly advanced respiratory symptoms, a more potent antiviral might be able to save more lives,” Hayden said February 2 in an interview at a conference in Washington. Shares of BioCryst rose 67 cents, or 6.6%, to $10.78 as of 9:47 a.m. New York time in Nasdaq Stock Market composite trading. They had lost 49% in the 12 months before today. Bird keepers and agriculture officials are losing a worldwide battle against H5N1 in birds, said Robert Webster, a US government-supported bird flu expert, at a conference in Washington last week. UK scientists today are culling 150,000 turkeys and trying to determine how the virus invaded an east England poultry farm.

Worldwide, H5N1 is known to have infected 271 people in 11 countries since 2003, killing 165 of them, the WHO said on February 3. Millions could die if the virus becomes as contagious as seasonal flu, touching off a pandemic. BioCryst is seeking regulatory approval to perform clinical trials in Asian countries to treat avian flu and severe flu cases, said James Alexander, the company's senior vice president of clinical and regulatory operations. „If Dr. Hayden is going to take that proposal to the steering committee at WHO and move forward, we're very much behind that,” he said yesterday in a telephone interview. Flu invades cells and hijacks their genetic material to make more viruses, which go on to infect more cells. Tamiflu, the drug made by Basel-based Roche that governments and the WHO have stockpiled to fight a possible pandemic outbreak, London-based GlaxoSmithKline Plc's inhaled Relenza antiviral and peramivir all target neuraminidase, a protein that enables newly created viruses to exit cells.

Doctors in Asia are preparing to test various doses of Tamiflu in patients with H5N1 and severe seasonal flu. Permission to use experimental doses of peramivir will be needed in countries, such as Indonesia, where the treatments could be used, Hayden said. After taking Tamiflu pills, patients build levels of the drug in their bloodstream as high as about 300 micrograms to 400 micrograms per milliliter. Human studies on peramivir, conducted with the US National Institutes of Health and released in September, indicate that infusing it into the bloodstream or injected it into muscles can produces levels rise of as much as 40,000 nanograms per milliliter, or levels 100 times higher than that seen with Tamiflu pills, Hayden said.

Birmingham, Alabama-based BioCryst's drug has been shown to fight H5N1 in the test tube and animals, and the company received $103 million from the US Department of Health and Human Services for development last month. Peramivir has been studied in people taking daily doses ranging from about 30 milligrams to 600 milligrams for as long as 10 days. The recommended dose for Tamiflu is 75 milligrams twice a day for five days, and the recommended treatment for inhaled Relenza is 10 milligrams twice daily for five days. Alternatives to Tamiflu may also be needed if more strains of the virus turn out to be resistant to the Roche drug, Hayden said. Scientists in Egypt, Italy and the UK are examining a strain that killed two people after they were treated with the drug. When scientists analyzed the virus in a laboratory, it showed a genetic change that made it less sensitive to Tamiflu, otherwise known as oseltamivir. While rare, genetic mutations that give H5N1 resistance to Tamiflu or make it less sensitive to the drug's antiviral properties have been found in birds, Hayden said.

„If there were widespread presence of a variant with reduced susceptibility to oseltamivir, one would need to consider additional management options in people who might have been exposed,” he said. Some Tamiflu-resistant strains have been shown to be susceptible to treatment with Glaxo's Relenza, Hayden said. Other experimental drugs that doctors might use to treat H5N1 include Daiichi Sankyo Co.'s CS8958, a topical drug, Toyama Chemical Co.'s oral T-705, and Nexbio Inc.'s DAS181, another topical treatment. The international health agency is planning a number of efforts to improve treatment for avian flu patients, Hayden said. The group will sponsor a March meeting in Turkey – which has had 12 cases of the disease, including four deaths –focused on improving treatment. Doctors from all 11 countries where cases have been confirmed will attend, Hayden said. That includes Indonesia, which has had 63 deaths, the most in the world, Azerbaijan, Cambodia, China, Djibouti, Egypt, Iraq, Nigeria, Thailand, and Vietnam. The health organization is also working to expand the range of patient information on its database of H5N1 cases, Hayden said. WHO would like to collect more data on the symptoms patients have when they arrive at hospitals and doctors' offices, what treatments are given, and how patients fare afterwards, he said. (Bloomberg)