Roche May Grant Tamiflu Licenses

Accused of not doing enough to boost global supplies of Tamiflu, an antiviral drug that may be effective against the avian flu, patent-holder Roche has offered to allow others to produce the pharmaceutical, known generically as oseltamivir phosphate.

We are prepared to discuss all available options, including granting sublicenses, with any government or private company who approaches us to manufacture Tamiflu or collaborate with us in its manufacturing, William M. Burns, CEO of Roche Pharma, said in a statement.

Some are already gearing up to supply Tamiflu. Taiwan's government has produced small quantities of the drug. Cipla, an Indian maker of generic drugs, expects that it will be able to mass-produce Tamiflu within three months and says it does not need Roche's consent to proceed.

I am not intending to sell the product where there are valid patents, says Cipla Chairman Yusuf K. Hamied. He notes that India has yet to grant Roche a patent on Tamiflu, and that Cipla will object if the patent is granted. Cipla hopes to sell Tamiflu in India and 49 less developed countries where the company already sells AIDS treatments, Hamied says.

But hopeful suppliers face serious difficulty in obtaining the key raw material, (–)-shikimic acid. A major source is China, where it is extracted from star anise. Hamied claims that Roche has cornered the Chinese (–)-shikimic acid market by signing supply contracts with most suppliers, and that any alternative source now demands prohibitive prices. Roche also manufactures the material by a proprietary fermentation process (C&EN, Aug. 29, page 22).

Even if a company can get (–150;)-shikimic acid, producing Tamiflu is a daunting task requiring 10 major steps and taking as long as 12 months. Roche insists that its familiarity with the manufacturing means it is best able to increase output. The process involves using potentially explosive sodium azide to introduce nitrogen into the molecule. But Hamied says similar steps are required to produce AZT, an AIDS drug Cipla has made since 1991.

Roche maintains that it is doing its utmost to increase Tamiflu's production. The company says it can still fill most orders within about a year. And along with its licensing offer, it announced that FDA has just granted it the right to open another capsule manufacturing plant in the U.S. Furthermore, commenting on the offer to license to others, a spokeswoman in Switzerland confirms to C&EN that Roche may also share its know-how in the manfacturing of (–)-shikimic acid.

Meanwhile, further complicating the development of public health strategies, resistance to Tamiflu has appeared in the avian flu virus isolated from a Vietnamese patient (Nature 2005, 437, 1108; C&EN Online, Latest News, Oct. 17).