By Lisa Seachrist
With the start of the influenza season looming in one month, Glaxo Wellcome Inc., a U.S. subsidiary of London-based Glaxo Wellcome plc, is working to fill pharmacy shelves and educate physicians about the benefits of its recently approved influenza therapy, Relenza.
In the meantime, Hoffmann-La Roche Inc. is waiting to hear whether the FDA will approve its anti-flu drug, Tamiflu (formerly GS4104). Because the drug has received an expedited review, the agency has until Oct. 29 to make its decision.
Should Tamiflu attain approval at the end of the month physicians will have not just one but two therapies that lessen the severity of the flu to offer to the approximately 40 million Americans who develop the viral illness. That choice could set up a battle for this newly emerging health-care market.
"It's really unclear how big this market is," said David Batter, an analyst with Mehta Partners LLC in New York. "Depending on how these drugs end up being used, they could be real blockbusters. It should be kind of fun to watch this battle and see who comes out on top."
Glaxo commenced the battle with some strong opening salvos last week at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Research Triangle Park, N.C.-based Glaxo presented 13 different papers on the efficacy of Relenza (zanamivir) including one that showed the drug worked on influenza B and another that showed the drug, taken prophylactically, could help prevent the spread of the flu from infected family members to uninfected ones.
The double-blind, placebo-controlled trial looked at the ability of Relenza to prevent the spread of the flu - both strains A and B - from one infected family member to another. Individuals with influenza-like illness during flu season were randomized to receive either treatment with Relenza (10 milligrams twice daily for five days) or placebo. Their healthy family members received the same blinded medication for prevention but took the medication for 10 days.
Relenza reduced the risk of catching the flu from a family member by 79 percent. Nineteen percent of families had one or more members develop the flu while only 4 percent of the families receiving Relenza prophylaxis had anyone develop the flu. The results, in combination with a flu prevention study conducted in college students taking Relenza as a prophylaxis for 28 days, could eventually support a labeling change.
"We won't be promoting off-label for prophylaxis," said Glaxo spokeswoman Karen Collins. "We are hoping to file a supplemental [new drug application] for the prophylaxis indication in the 4th quarter of this year."
Relenza, developed by Melbourne, Australia-based Biota Holdings Ltd. and licensed to Glaxo, is the first in a class of new drugs called neuraminidase inhibitors. It is a rationally designed drug that inhibits the neuraminidase enzyme on the surface of the flu virus. Neuraminidase facilitates the influenza virus' ability to spread from cell to cell in the respiratory tract.
Relenza, an inhaled therapeutic, is designed to stop the function of neuraminidase and limit the course of disease. Taken early enough after infection, Glaxo has shown the drug eliminates symptoms 1.5 to 2 days sooner than placebo. To date, it is the only approved flu therapy active on both the A and B strains of influenza. The drug was approved by the FDA in July. (See BioWorld Today, July 28, 1999, p. 1.)
The publicity from ICAAC could work to give the inhaled Relenza an advantage over Roche's oral Tamiflu even if that drug receives approval in time for this year's flu season. It is also possible the Relenza publicity could benefit Tamiflu by heightening the awareness of influenza treatments.
"The data that came out of ICAAC really didn't raise the competitive bar," said Caroline Copithorne, senior analyst with Prudential Vector Healthcare Group in New York. "It gave Glaxo more exposure and publicity, which expands the market. But, the audience at ICAAC won't be the physicians who will be prescribing the drug. I don't think this gives them a prescribing edge."
Copithorne noted the physicians attending ICAAC tend to be infectious disease specialists and oncologists. It will be the general practitioner and primary care doctor who will prescribe Relenza and, should it be approved, Tamiflu. At the prescribing level, Copithorne and Batter agree Tamiflu may have an advantage.
"A lot of people give Tamiflu the advantage because its an oral formulation," Batter said. "It a more convenient formulation than an inhaled formulation."
Tamiflu, a neuraminidase inhibitor in pill form, was developed by Gilead Sciences Inc., of Foster City, Calif., and licensed to the Nutley, N.J.-based Hoffmann-La Roche Inc. Roche filed a new drug application for the drug in May, just 26 months after the very first patient had been dosed. (See BioWorld Today, May 3, 1999, p. 1.)
Tamiflu was granted an expedited review and was scheduled for an advisory panel hearing in September. The FDA, however, decided to cancel the panel hearing without citing a reason. Copithorne views that as a positive sign because the agency usually cites deficiencies as the reason when canceling a panel hearing.
"[Roche] got approval in Switzerland and that supports the case for the drug," Copithorne said. "To have an approval in another country and to see the panel meeting canceled, that bodes well."
The key for one drug pulling ahead of the other could be the prophylaxis indication. With that indication, it becomes possible for patients to have the drug sitting in the medicine cabinet in anticipation of flu season. Both Batter and Copithorne agree primary care physicians are unlikely to prescribe the drugs off-label for an otherwise healthy group of people.
"Getting the prophylaxis label will be important for next flu season," Copithorne said. "It will allow a lot more direct-to-consumer advertisement for patients."
Glaxo has presented much of its prophylaxis data, while Roche is developing data to support such an indication as well.
Waiting in the wings are two other flu products in development. BioCryst Pharmaceuticals Inc., of Birmingham, Ala., has an oral flu drug, RWJ-270201, in development with Johnson & Johnson of New Brunswick, N.J. Batter said that drug is unlikely to garner an expedited review and likely will not be ready before the 2002 flu season.
In addition, Aviron, of Mountain View, Calif., is planning on filing a biologics license application for its nasal influenza vaccine, FluMist, this year.
"Nobody has ever tried to treat the flu like this before," Batter said. "It's really hard to say what the impact will be, but the market could be quite large."