Relenza vs Tamiflu

Glaxo's Relenza Is Less Likely to Cause Resistant Flu Strains

Aug. 18 (Bloomberg) -- GlaxoSmithKline Plc's Relenza antiviral treatment is less likely to lead to drug-resistant flu strains than Roche Holding AG's Tamiflu, giving the product an edge against a feared pandemic, a Glaxo-sponsored study found.

Tamiflu is recommended by the World Health Organization as the first choice for doctors treating human cases of avian influenza. A Tamiflu-resistant strain of the H5N1 virus killed at least three people in Vietnam, raising concern about the drug's potency should H5N1 spark a pandemic.

Human flu strains created to be resistant to Relenza were weakened and less viable when studied test tubes in the laboratory. The study, to be published in this month's edition of the Journal of Antimicrobial Chemotherapy, was undertaken by Glaxo's Medicine Research Centre in Stevenage, England, and an Australian government scientific organization.

``It appears that mutations that confer Relenza resistance compromise the ability of the virus to survive and multiply,'' said Jennifer McKimm-Breschkin, a virologist at the Commonwealth Science and Industrial Research Organization in Melbourne. The finding may explain why no cases of Relenza-resistant flu have been found in normally healthy adults, she said in a telephone interview yesterday.

McKimm-Breschkin was a member of a team that developed London-based Glaxo's Relenza, which is also known by its chemical name, zanamivir.

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

Different Molecules

The two drugs have a different molecular structure. Zanamivir more closely resembles the sugars coating cells which the virus has to remove in order to spread, McKimm-Breschkin said. Mutant flu viruses that lose the ability to bind with zanamivir also lose the ability to remove the sugars and subsequently can't spread and reproduce, she said.

``It has always been more difficult to get zanamivir resistant mutants than oseltamivir-resistant mutants in the laboratory,'' said K.Y. Yuen, head of the microbiology department at the University of Hong Kong.

Hong Kong has a policy of recommending Relenza as a safeguard to any health care worker caring for an avian flu patient being treated with oseltamivir, Yuen said in an e-mail yesterday.

For health workers, ``Relenza should be considered as a prophylaxis since they may have a risk of getting an oseltamivir- resistant flu virus from these patients who may be brewing them up during treatment,'' he said.

Preferred Choice

Oseltamivir, taken orally in capsules, is the preferred drug for treating avian flu cases because the medicine is easier to administer than zanimivir, which is inhaled. It also is circulated in the bloodstream around the body, unlike zanamivir, which is taken up by tissues mostly in the upper airway and may not kill virus outside the lungs.

Only 4 percent to 17 percent of the total amount of the orally inhaled Relenza is absorbed by multiple organs, according to a study published in 1999 in the journal Clinical Pharmacokinetics.

Infection caused by seasonal flu is typically confined to the upper respiratory system. Avian flu has been shown to infect numerous parts of the body, including the gastrointestinal system, blood and cerebral spinal fluid, according to Menno de Jong, head of the virology department at the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam.

De Jong's team was the first to report human avian flu cases caused by Tamiflu-resistant H5N1 strains.

New Version?

Relenza isn't made in pill form because the drug can't enter human cells and tissues properly by that route, Jennifer Armstrong, a Glaxo spokeswoman said last month. Glaxo is in the early stages of studying the possibility of a version that could be administered directly into the bloodstream, she said.

``If an intravenous or oral preparation of zanamivir is finally available, it will replace oseltamivir whose only superiority is good systemic blood level,'' said Yuen.

Relenza sales rose 70 percent to 5.2 million pounds ($9.8 million) in 2005. Roche's Tamiflu brought in 1.6 billion Swiss francs ($1.3 billion) last year.

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