By Mary Welch

Staff Writer

Flu sufferers may be breathing a little easier this year as the FDA approved Relenza (zanamivir for inhalation), a therapy for both influenza A and B, that was developed by Biota Holdings Inc. and licensed to Glaxo Wellcome plc.

"The approval means the FDA is moving ahead despite the advisory committee's decision, which is important to note," said Viren Mehta, an analyst with Mehta Partners LLC in New York. "You don't often see that."

In fact, the Antiviral Drugs Advisory Committee voted 13-4 against recommending approval, citing a North American pivotal trial that failed to show statistically significant benefit to flu suffers. (See BioWorld Today, Feb. 25, 1999, p. 1.)

"Basically, the advisory committee got sidetracked," Mehta said. "It was not the objective of that committee to get bogged down in areas such as whether a person could self-administer the drug. Based on clinical trials, done in part in discussions with the FDA, the questions should have been: 'Did the committee find the data persuasive? Did it turn out to be safe and effective?' That was the mission. The FDA hinted at and obviously felt that the data showed it was safe and effective."

He added, "As we all know, the committee does have its own personality and that personality changes day to day."

The drug is indicated for the treatment of uncomplicated acute illness due to influenza virus in adults and adolescents ages 12 or older who have been symptomatic for no more than two days. Patients inhale Relenza using a hand-held, breath-activated device called a Diskhaler. A couple of puffs delivers Relenza to the surface of the lungs, the primary site of influenza infection, where the drug is believed to inhibit the virus from multiplying. Relenza reduces the duration of flu-related symptoms when administered within the first two days of symptoms. Patients inhale 10 mg of Relenza twice a day for five days.

Relenza belongs to a new class of compounds called neuraminidase inhibitors. An enzyme, neuraminidase breaks the bond holding new virus particles to the infected cell. Once broken, the new viruses are free to infect other cells, spreading the infection. Relenza is thought to work by inhibiting breakage of the bond and preventing release of the new viruses, interrupting the spread of infection within the respiratory tract.

Data showed that Relenza reduced the severity of fever, myalgia, weakness, cough and loss of appetite. Developed by Biota of Melbourne, Australia, Relenza received European marketing approval last month. It was approved in Australia in April. (See BioWorld Today, June 7, 1999, p. 1.)

Since the flu affects between 25 million and 50 million people in the U.S. annually, the potential market is huge. The direct and indirect costs of flu-related healthcare are about $12 billion a year. Influenza causes 20,000 to 40,000 deaths a year.

Although Relenza is the first drug for influenza A and B approved, it likely won't be the only one for long. By the time of the onset of the 1999-2000 flu season, generally starting around November, a competitor presumably will be on the market.

Gilead Sciences Inc.'s drug, GS4104, a neuraminidase inhibitor in pill form, is expected to be FDA approved within months. The company's partner, Nutley, N.J.-based Hoffmann-La Roche Inc., submitted the drug to the FDA in May. The FDA panel meeting is set for September and since the drug received a priority review, a decision should be made by late October.

"Glaxo has done a great job at softening the market for the launch of a new class of drugs," said Mike King, senior analyst with BancBoston Robertson Stephens Inc. in New York. "They've been very aggressive with this blockbuster category. It's not a case of one drug doing well and the other not. It's not an either-or situation."

King expects GS4104, developed by Foster City, Calif.-based Gilead, to do about $77 million its first year.

"I haven't broken the numbers down but I'd say both drugs will garner about the same [sales] numbers," King said. "If you look at efficacy, they're comparable. It'll become a marketing battle between the inhalation therapy and pills. Now some people don't want to take pills and would prefer the inhaled method. Others won't mind."

Mehta said Relenza could reach $350 million in sales by 2003. "At the time we made that estimate, we thought Glaxo would have certain restrictions but the label is rather clean," he said. "We expect to increase our forecast."

Although pricing was not revealed, King said he expects the Gilead-Roche drug to cost about $65 per course of treatment, with Relenza presumably similar in pricing.

This approval, Mehta said, shows the "FDA is moving consistently, predictably and keenly in having the fruits of new science reach the public as soon as possible. That bodes well for the industry, Glaxo and Gilead Sciences."