By Kim Coghill

Washington Editor

GAITHERSBURG, Md. ¿ A government panel of scientists Friday said efficacy data for Aviron Inc.¿s nasal vaccine against the flu in children and adults is adequate.

But the safety data, presented by the company in a two-day public meeting of the Vaccines and Related Biological Products Advisory Committee, was not sufficient enough to win the committee¿s recommendation for approval.

In a press conference after the hearing, Boyd Clarke, Aviron¿s chairman and CEO, said of the vote, ¿We won¿t make our secondary objective this year, which was a partial launch in the 2001 flu season. But our primary objective has always been a launch in the 2002-2003 flu season. We will work with the FDA toward that.¿

The product, FluMist, has been the subject of numerous trials that involved about 24,000 patients ages 1 to 64. The drug is a cold-adapted trivalent vaccine containing two different influenza A strains and one influenza B strain selected each year based on worldwide surveillance. The internal flu proteins from the master strains of influenza A and B virus grow at cooler temperatures and combine with hemaglutinin and neuraminidase, the surface proteins found on contemporary circulatory viruses. FluMist stimulates the mucosal immune system as well as the systemic immune system, resulting in a strong cytotoxic T-cell response. Other flu shots on the market contain killed viruses.

Clarke told reporters not to lose sight of the fact that the panel agreed on efficacy. ¿I¿m pleased with the positive vote on efficacy in such a wide range of individuals. Clearly we would rather that the safety vote had turned out differently,¿ Clarke said. ¿You can¿t go through a day like today without being disappointed, but I think there have also been accomplishments.¿

The committee voted 8 to 7 saying FluMist showed efficacy in patients ages 1 to 17 years. Most of the seven who voted ¿no¿ were opposed to giving the medicine to children under 1. Five of the seven recommended that the youngest be 15 months or 2 years.

¿I¿m not real sure about under 2,¿ Walter Faggett, a committee member and pediatrician in Washington, said. ¿As a practicing pediatrician, we are excited about a vaccine that is easily administered. We think it will close the gap on disparity.¿

Barbara Fisher, committee member and co-founder and president of the Vienna, Va.-based National Vaccine Information Center, voted against the efficacy in children, saying more data in children are necessary. ¿I can appreciate the task of trying to develop a vaccine for such a large patient population, but I would like to see more data in children under 5 years old. I would suggest about 3,000 children over a two-year period.¿

The committee also vacillated on whether children should be given one or two doses, prompting committee member Theodore Eickhoff, a professor of medicine at the division of infectious diseases at the University of Colorado Health Services Center in Denver, to recommend two doses for children. ¿It might be overkill and later data may show it is not necessary.¿

But Robert Daum, committee chairman and professor of pediatrics at the University of Chicago Children¿s Hospital, said he had not heard any data indicating the necessity of more than one dose for children.

Aviron recommended administering two doses of FluMist at least one month apart for children under 9. The company said two doses would provide the maximum protection.

In the efficacy of adults, the committee voted 13 to 2 in favor of FluMist.

Eickhoff, who did not agree that FluMist showed efficacy in adults, said, ¿There¿s no doubt FluMist is effective in healthy adults. The question is, how effective? The inactivated vaccine is adequate and the live vaccine may not be effective.¿

But citing a lack of data, the committee voted 10 to 4 that trials did not prove FluMist is safe.

¿I think the overall safety profile is good, but I have concerns about asthma and pneumonia,¿ said Nancy Cox, committee member and chief of the influenza branch at the Centers for Disease Control and Prevention in Atlanta. ¿We all know the data is incomplete and we look forward to seeing more data.¿

Daum agreed that the data were incomplete, but voted in favor of the safety, saying it is a work in progress. ¿I believe a tremendous amount of progress has been made with this drug and I am excited about this.¿

Clarke pointed out that most committee members agreed that FluMist looks good from a safety standpoint, ¿they just want more data. We¿ve got the data and now we are clear on what the issues are.¿

He didn¿t release any type of time frame regarding the next step, but did say, ¿Aviron had over $500 million in the bank at the end of the last quarter and we are committed to this product.¿

FluMist Expected To Be Multimillion-Dollar Product

Analysts range in their predictions on revenue FluMist will generate. Douglas Lind, a physician with Morgan Stanley in New York, said by 2005, FluMist should bring in about $320 million for the company, but others estimate higher amounts, anywhere from $500 million to a billion dollars at its peak.

Once it lands on the market, FluMist will be the first preventative flu product administered nasally.

In 1999 two other flu products entered the market, but Aviron officials say both are a little different and essentially don¿t pose competition. The first is Relenza, a therapy to treat A and B strains of influenza, marketed by London-based GlaxoSmithKline plc. The other is Tamiflu, a neuraminidase inhibitor in pill form developed by Hoffmann-La Roche Inc., of Nutley, N.J., and Gilead Sciences Inc., of Foster City, Calif.

Aviron will market FluMist with Wyeth Lederle Vaccines, a business unit of the pharmaceutical division of American Home Products Corp., of Madison, N.J.

Aviron began pivotal trials in 1996 for FluMist. Two years later, the FDA rejected the company¿s biologics license application, citing a need for more manufacturing data. (See BioWorld Today, Sept. 2, 1998.)

The company resubmitted an application last fall and it was accepted in December, triggering a milestone payment from Wyeth Lederle Vaccines.

Aviron also is involved in the Phase II study of Liquid FluMist, which would be used in international markets where frozen storage is mostly unavailable. The company is developing a parainfluenza virus type III vaccine to prevent the most common cause of croup. Along with partner GlaxoSmithKline plc, of London, Aviron has begun Phase II trials with an Epstein-Barr virus subunit vaccine.

Trading on Aviron¿s stock (NASDAQ:AVIR) was held Friday, with the stock at $40.80.