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July 2003 • Volume 37 • Number 7

News

More expensive than injected
FluMist Licensed For Ages 5-49 Years

Miriam E. Tucker
Senior Writer

ATLANTA — The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has endorsed the use of FluMist as “an important new option” for vaccinating healthy individuals aged 5-49 years.

The new intranasal trivalent, cold-adapted, live attenuated influenza vaccine (LAIV) is manufactured by Medimmune Inc. and comarketed by Wyeth Vaccines. The Food and Drug Administration licensed the vaccine the day before an ACIP meeting, where the committee drafted recommendations for its use. Its label will call for a two-dose regimen (60 days apart) for first use in healthy children aged 5-8 years and one dose for individuals aged 9-49 years, FDA reviewer ChrisAnna Mink told ACIP.

According to Dean Mason of the CDC's National Immunization Program, the production target of FluMist for the 2003-2004 influenza season is expected to be about 4-6 million doses. The vaccine will be shipped directly from Wyeth Vaccines to U.S. physicians. The price range will be $45-$50 per dose, which few health insurance companies are expected to cover the first year out.

“Most purchases in year one will be out-of-pocket to the consumer,” Mr. Mason said, adding that coverage through the Vaccines for Children program also is likely to prove problematic, due to both the cost and the storage requirements: The vaccine must be kept frozen at less than 5° F or below.

American Academy of Pediatrics liaison Carol Baker said, “I think FluMist is a useful addition to the influenza prevention program. It will give certain families more choices.”

But, she added, “I would have liked to have seen a vaccine for younger children. I think it will be much more useful when it's licensed for children down to at least 12 months, and I'd like it for ages 6 months and above. I think the company will be motivated to continue studies,” Dr. Baker, professor of pediatrics and head of infectious diseases at Baylor College of Medicine, Houston, said in an interview.

The AAP has posted guidance regarding FluMist on its Web site, www.aap.org.

In clinical trials involving 544 healthy children aged 60-84 months, FluMist was 86%-93% effective in preventing influenza and was associated with a 30% reduction in febrile otitis media.

Among 4,303 healthy working adults aged 18-64 years who were studied during influenza outbreaks, the vaccine reduced the number of severe febrile illnesses by 17% and febrile upper respiratory illnesses by 22%, the FDA's Dr. Mink reported.

Assumed efficacy in children aged 9-17 years was extrapolated from the data in younger children and in adults, she said.

Adverse reactions in both children and adults included runny nose, nasal congestion, and headache. Children also experienced fever, occasional vomiting, abdominal pain, and myalgias, while adults also reported sore throat. Most reactions were self-limited; there were no serious adverse events.

The company originally had sought an indication for use in healthy people aged 1-64 years, but the FDA denied it because of a 3.53-fold increased risk for asthma events after the first dose in children 12-59 months of age and because the number of adults over age 50 studied (641) was not enough to demonstrate efficacy.

Medimmune plans to gather more data to seek expanded indications for use in adults aged 50-64 years, children less than 5 years, and high-risk populations, said Dr. Edward M. Connor, the company's senior vice president for clinical development.

The ACIP's document on FluMist (referred to as “LAIV”), which is still undergoing minor revisions and is expected to be released in midsummer, recommends the new product “as an option for vaccination of healthy persons aged 5-49 years, including persons in close contact with high-risk groups and those wishing to avoid influenza.” Advantages include its potential to induce a broad mucosal and systemic response, ease of administration, and the acceptability of an intranasal rather than an intramuscular route of administration.

The list of people who should not receive LAIV includes all of the high-risk groups for whom the injectable trivalent inactivated vaccine (TIV) is recommended: People aged 50 years and older; those with high-risk chronic pulmonary, metabolic, and immunosuppressive medical conditions; children receiving aspirin or other salicylates; and pregnant women. Neither vaccine should be used in people with a history of Guillain-Barré syndrome or those with egg hypersensitivity.

It is unknown whether administering influenza antiviral medications affects the safety or efficacy of LAIV, so the vaccine should not be administered until 48 hours following the cessation of antiviral therapy, nor should antivirals be given for 2 weeks following receipt of the vaccine.

Also, there are no data on transmission of LAIV from vaccine recipients to immunosuppressed contacts, so the use of the TIV is preferred for vaccinating household members, health care workers, and others who have close contact with immunosuppressed individuals because of the theoretical risk that a live vaccine could be transmitted.

The committee discussed the transmission issue at length, particularly with regard to health care workers. Committee members pointed out that currently about 70% of health care workers do not receive yearly influenza vaccines—and therefore pose an even greater risk of passing along the infection—and that in surveys 15% of health care workers report a fear of needles.

The document will also include information about dosing and administration of LAIV as well as storage, which could prove troublesome for some practices. Because the defrost cycle temperature of most frost-free freezers is too warm for FluMist, the vaccine must be kept in a special insulated box supplied by the manufacturer. One ACIP liaison remarked that the box is quite large and may not fit into the refrigerators that physicians currently have in their offices.

But James Young, Ph.D., Medimmune's president for research and development, told this newspaper, “The vast majority of doctor's offices will accommodate the FluMist freezer box, so we don't envision a storage problem for the vaccine.”