Washington Editor

BETHESDA, Md. - By dropping children younger than 5 from its label, MedImmune Inc. was able to convince an FDA panel of experts that the intranasal influenza vaccine FluMist is safe and efficacious in people ages 5 to 49.

If all goes well at the FDA, FluMist, a potential blockbuster, could be on the market in time for the 2003-04 flu season, MedImmune CEO David Mott said.

While a majority on the Vaccines and Related Biological Products Advisory Committee (10 to 8) said FluMist was safe in the 50- to 64-year-old population, only four of 18 members agreed that it was efficacious in that group.

"You get older, you smoke, you get fat and you don't respond as well to vaccines after 60," Samuel Katz, a panel member and Wilburt C. Davidson professor and chairman emeritus, department of pediatrics at Duke University Medical Center in Durham, N.C., said. "I would like to see more data."

The panel did not vote to recommend FluMist for approval. Instead, the group cast separate votes on whether the intranasal squirt was safe and efficacious in three age groups: 5 to 17, 18 to 49 and 50 to 64. If approved it would be the only intranasal influenza vaccine in the United States.

David Mott after the meeting would not discuss potential pricing strategies. Some investors in the audience speculated the vaccine would cost $40.

"The age population that was approved was 5 to 49," Mott said. "Obviously, we will be talking with the FDA in the next few months to add the remaining population."

The advisory committee recommends actions to the FDA, which is not bound by the recommendation.

In the younger populations, FluMist sailed through with near-unanimous votes in each category. Only Barbara Loe Fisher, co-founder and president of the National Vaccine Information Center in Vienna, Va., opposed FluMist in every category, saying it's a major step to inject live virus in healthy people.

FluMist contains three strains of live, attenuated, cold-adapted, temperature-sensitive influenza virus: two Type A (H1N1 and H3N2) and one Type B. FluMist has been studied in 20,000 patients ages 1 to 64, who participated in 20 trials.

MedImmune's biologics license application (BLA) requests a label for prevention of disease caused by influenza A and B viruses in healthy children and adults, 5 years through 64 years of age.

The original BLA was submitted back in October 2000 by then-owner Aviron Inc., the Mountain View, Calif.-based company that ran into trouble at its two-day panel meeting in July 2001.

While the earlier panel agreed that FluMist was efficacious in 18- to 64-year-old healthy people (13 to 2 vote in favor), it was split (8 to 7 against) for 1- to 17-year-olds. But the real problem was safety, or rather, the lack of safety data. In a 9 to 5 vote, the panel said Aviron's FluMist safety data were insufficient in people aged 12 months to 64 years. (See BioWorld Today, July 30, 2001.)

Within six months, Aviron signed a $1.5 billion deal to merge with MedImmune, of Gaithersburg, Md. As a carry-over from the Aviron ownership, FluMist remains partnered with Wyeth, of Madison, N.J. for U.S. marketing rights (See BioWorld Today, Dec. 4, 2001.)

Since taking on the nasal spray, MedImmune has revised the BLA twice: once on March 15 for people 19 months to 64 years, and again on Nov. 1 for people 5 to 64 years old.

Another difference since last time is that MedImmune went to the panel Tuesday with a full set of safety and efficacy data from 20 trials, including 14 randomized, double-blind, placebo-controlled studies (three were pivotal) and six open-label trials. Or so it thought.

Most members simply thought the data were inadequate for the 50-64 age group. But according to the FDA, the four efficacy studies submitted as part of the original BLA demonstrated efficacy or effectiveness in FluMist as compared to placebo (two studies were in children and the other two were in adults).

Taking care of the safety problem from two years ago, MedImmune on Tuesday presented data from Study AV019, also known as the northern California Kaiser Permanente trial of 9,689 children aged 12 months to 17 years. Trial participants were randomized in a 2-to-1 ratio to receive FluMist or placebo. ChrisAnna Marie Mink, an FDA reviewer, said there was an increased risk of asthma among FluMist recipients aged 18 months to 35 months.

The FDA also presented study AV012, or the Texas HMO trial, conducted among 7,448 children aged 18 months to 18 years who lived in Temple-Belton, Texas. Cautioning the trial was not controlled, blinded or randomized, the FDA said, "The reported rate of serious adverse events were low and other rare events potentially associated with influenza were not observed during the 42-day post-vaccination."

And in Wyeth DP145-500, a randomized, double-blind study of 200 Finnish patients aged 8 months to 36 months, the company tried to provide estimates of shedding (release of the virus possibly through a sneeze) and vaccine transmission among daycare attendees.

Mink said that while that study was limited, such as by small size and protocol deviations, data showed that viral shedding did occur following receipt of FluMist (in the range of 80 percent) and persisted in some FluMist patients up to 21 days. Transmission of the vaccine also occurred.

To that, Robert Daum, chairman and professor of pediatrics at the University of Chicago Children's Hospital, spoke in conjunction with many of his colleagues who said they would like to see more data on shedding. "And I would like to see data on the people who are impacted by the shedding," he said.

For efficacy in children aged 15 months to 71 months on entry, MedImmune presented data from Study AV006, a randomized, double-blind, placebo-controlled two-year trial of 1,602 healthy participants. The company said FluMist's efficacy was 93 percent against culture-confirmed influenza, the primary endpoint.

In adults, MedImmune presented the trial AV009, a randomized, double-blind, placebo-controlled study of 4,561 healthy adults aged 18 to 64. The primary endpoint was demonstrating a smaller portion of FluMist patients with "any febrile illness" (fever). According to the analysis provided by the FDA, there was no significant difference in effectiveness, i.e., in occurrence of any febrile illness during site-specific outbreak periods.

Severe febrile illness and febrile URIs (runny nose, sore throat, cough) were less common in FluMist patients than in placebo patients.

Trading on MedImmune's stock (NASDAQ:MEDI) was held Tuesday.