Jan. 28 (Bloomberg) -- Roche Holding AG's Tamiflu may be losing potency against seasonal influenza in Europe after tests showed resistance to the drug in more than one of 10 samples.

Tests on 148 virus specimens from patients with the H1N1 flu strain in 10 European countries found 19 that harbored resistance to the pill, most of them in Norway, the European Centre for Disease Prevention and Control said today.

The results show viruses capable of evading Tamiflu, also known as oseltamivir, may be spreading. Some resistant viruses were also found in the U.S., leading doctors to consider GlaxoSmithKline Plc's Relenza and other treatments for a disease the World Health Organization estimates causes 250,000 to 500,000 deaths globally each year.

``These preliminary results are in contrast to previous years where little or no resistance to oseltamivir was observed,'' Martina Rupp, a Roche spokeswoman, said in an e-mail today. More surveillance is needed to establish the prevalence and geographical distribution of the resistant H1N1 variants and to assess the impact on Tamiflu's effectiveness, she said.

Basel, Switzerland-based Roche has ``informed health authorities worldwide about this situation,'' Rupp said.

Roche fell 1.8 Swiss francs, or 0.9 percent, to 192.2 francs in Zurich trading. The shares have dropped 1.7 percent this year.

`High-Level Resistance'

The H1N1 viruses identified in Europe that aren't susceptible to Tamiflu carry a so-called H274Y gene mutation that confers ``high-level resistance,'' said Frederick Hayden, a researcher with the WHO's Global Influenza Program in Geneva.

Preliminary data from the U.S. Centers for Disease Control and Prevention in Atlanta ``indicate that there have been some of these kinds of resistant variants detected, albeit at low frequency, in the U.S.,'' Hayden said. Teleconferences will be held this week to gauge their geographic distribution, he said.

Of 204 viral samples tested by the CDC during the 2007-2008 flu season, six, or 2.9 percent, were resistant to Tamiflu. All those resistant samples were among 109 H1N1 viruses, for a rate of 5.5 percent in that strain, said Joseph Bresee, chief of the epidemiology and prevention branch of CDC's influenza division in Atlanta.

``It bears watching,'' he said today in a telephone interview. ``Our recommendations for use of oseltamivir haven't changed, but we're going to continue to do close monitoring on flu viruses from here on out.''

`Unexpected'

There's no evidence the mutation is associated with increased transmissibility or increased likelihood of causing disease, Hayden at the WHO said by telephone from Geneva today.

``This is an unexpected circumstance to see the circulation of H1N1 viruses harboring this particular mutation,'' he said.

Relenza and amantadine, an older class of antiviral medicine, are capable of fighting the mutant variant, health officials said. However, large numbers of flu viruses have other mutations that make them resistant to amantadine and a related drug, called rimantadine, Bresee said. Neither drug is recommended for treatment of seasonal flu in the U.S.

A WHO report last April said 2.2 percent of H1N1 samples from Japan, the world's biggest user of Tamiflu, had the H274Y mutation. There have been no reports from Japan of recent cases.

The samples tested in Europe were taken from patients who hadn't been treated with Tamiflu, and resistance rates varied from country to country, Hayden said.

Norwegian Cases

In Norway, 12 of 16 H1N1 samples taken from patients across the country this winter showed ``a high degree of resistance,'' the Norwegian Institute of Public Health said in a Jan. 25 statement. An H1N1 variant from the Solomon Islands is the dominant flu strain now circulating in the Scandinavian country and other parts of Europe, the Oslo-based institute said.

``It is disturbing that resistant viruses are now being detected in Europe, which has a very low level'' of antiviral use, said Jennifer McKimm-Breschkin, a virologist at the Commonwealth Science and Industrial Research Organization in Melbourne. ``This suggests that resistant viruses have obtained a growth advantage elsewhere on the globe, and have been sufficiently fit to now start spreading possibly globally even in the absence of widespread drug use.''

Tamiflu, which generated 2.63 billion francs ($2.4 billion) in sales for Roche in 2006, is the company's fourth-best-selling drug. Relenza, an inhaled medicine, had sales of 91 million pounds ($180 million) in the same year for London-based Glaxo.

Stockpiling

The medicines are being stockpiled by the Geneva-based WHO and governments around the world for use in the event of a pandemic, and to treat the H5N1 avian flu strain that's spread to more than 60 countries, infecting people in 14 of them.

``With the global focus on oseltamivir as the drug of choice for treating influenza, many clinicians are not even aware that there is an effective alternative: Relenza,'' McKimm-Breschkin said in a telephone interview today.

Relenza and Tamiflu work by blocking neuraminidase -- one of the two surface proteins in influenza viruses and the ``N'' in H5N1 and H1N1 -- that allows the virus to spread from infected cells to other cells in the body.

The H5N1 bird flu strain could trigger a global outbreak if it adopts some of the characteristics of seasonal flu that enable it to be spread easily through coughing and sneezing.

Seasonal flu strains with resistance to Tamiflu and other so-called neuraminidase inhibitors could potentially exchange genes with the pandemic strain, making the medicines a weaker weapon to fight the global contagion.

``Antiviral resistance to neuraminidase inhibitors has been clinically negligible so far, but is likely to be detected during widespread use during a pandemic,'' the WHO says on its Web site.

To contact the reporter on this story: Jason Gale in Singapore at j.gale@bloomberg.net

Last Updated: January 28, 2008 15:09 EST