FluMist may help reduce the burden of seasonal influenza

May 9 2007

MedImmune, Inc. has announced research results showing that use of FluMist(R) (Influenza Virus Vaccine Live, Intranasal) in daycare and school settings may help reduce the burden of seasonal influenza.

Economic analyses applied to outcomes observed in previously completed clinical studies suggest that influenza vaccination may provide a beneficial cost savings to the community at large. The results were presented at the annual meeting of the Pediatric Academic Societies (PAS) taking place this week in Toronto, Canada. Additional data were presented from a study showing that increased vaccination rates may help prevent late-season influenza B outbreaks, as well as from a post-licensure safety analysis of FluMist that showed that the vaccine was well-tolerated.

"The results of the various FluMist-associated clinical and pharmacoeconomic studies presented at the PAS meeting are encouraging both individually and collectively," said Robert Walker, M.D., vice president, clinical development. "These data show us that innovative influenza vaccination approaches may have benefits that extend beyond just protection of the vaccinated individual. Immunizing children at places where they gather such as schools and daycare is logical, since children are often the main source of the spread of influenza in a community."

Results from a previously completed and published placebo-controlled, two- season trial involving children aged 6 months to 36 months attending daycare centers showed that those children receiving FluMist experienced significantly fewer cases of influenza-like illness (ILI) (Vesikari, T, et.al., Pediatrics, 2006). New data presented at the PAS meeting estimate the economic impact of these clinical outcomes and find a potential societal cost savings associated with immunizing children against influenza. In the first year of the study, vaccination provided savings of approximately $5.47 per child, while in the second year of the study, the projected savings increased to almost $144 per child. The economic analysis also indicated that the significantly higher savings projected in the second year of the study were due in part to the substantially higher rate of influenza infection among the study population.

"From the societal perspective, influenza immunization of young children at daycare or school settings seems to make economic sense. By reducing influenza attack rates, there is less burden on the healthcare system and fewer days missed from school and work, which drive the societal cost savings," said Parthiv Mahadevia, M.D., MPH, senior director of health outcomes and pharmacoeconomics.

Data from a community-based study involving 15,000 children in 28 schools across four states (Maryland, Texas, Minnesota and Washington) showed that households of the 11 schools where children received FluMist reported statistically significant reductions in ILI, child doctors' office visits, medications and work/school absenteeism in the peak flu week as compared to the households of the 17 control schools where no influenza vaccinations were provided. The study, conducted by researchers at the University of Maryland Medical Center, was designed to determine the impact of school-based vaccination on children and households. All school households were asked to complete a survey on ILI symptoms, healthcare use (such as spending on over- the-counter medicines and healthcare provider appointments), and absenteeism from school and work (for direct illness or to care for a sick child) during the predicted peak week for influenza epidemics.

An analysis comparing control school households to target school households showed that the target school homes reported statistically significant reductions in ILI, child office visits, medications and work and school absenteeism in the peak flu week. In a per-household economic analysis of the data, it was projected that costs related to immunizing children were largely recouped through reduced healthcare use and fewer work absences compared to those in the control schools.

After the conclusion of the 2005-2006 flu season, researchers in a Maryland county examined the impact on school absenteeism rates of immunizing eligible students against influenza. In the study, more than 5,300 (44 percent) of the county's elementary school children at 21 public schools received FluMist. While absenteeism rates increased during the school-based vaccination program, researchers found that the rates rose less during the season among the FluMist intervention group. In elementary schools, the increase in absenteeism was three times greater in the control group than the intervention group (1.78 vs. 0.61 percent increase, p = 0.032). In addition, even though only elementary school children received vaccinations, researchers found an impact on absenteeism rates in middle and high schools as well. In middle schools, the rise in absenteeism in the control group was nearly three times that of intervention-group schools (1.84 vs. 0.61 percent increase, p = 0.12). In high schools, the increase in absenteeism was five times higher in control schools (1.80 vs. 0.32 percent increase, p = 0.003). This study was conducted as part of a public health initiative by the Carroll County Health Department and Public School System in Carroll County, Maryland.

At the PAS meeting, researchers in central Texas reported that immunizing less than one-third of children participating in influenza intervention programs appears to have reduced Medically Attended Acute Respiratory Illness (MAARI) caused by influenza type B when compared to age-specific expected rates.

In the study, nearly 29 percent of children 5 to 19 years of age were vaccinated (73 percent with FluMist; 27 percent with the flu shot) in the 2005-2006 season, in which influenza outbreaks occurred in two waves, with type A predominating early in the season, and type B in the later wave. Despite the higher pre-epidemic relative rate of MAARI in all age groups (particularly in children 5 to 17 years of age), there was a statistically reduced relative rate of MAARI in the B wave of the epidemic in two of the age groups and a suggestion of reduction in the others. There was no reduction of type A disease.

Interim data were also presented at the PAS meeting from an ongoing post- marketing safety evaluation that has thus far revealed no unanticipated safety concerns in the approximately 45,000 FluMist recipients assessed to date. Neither asthma/reactive airway disease nor wheezing/shortness of breath occurred at rates that were statistically significant in any age group in the risk period compared to the control period. In the study, interim results were analyzed for the 2003-2004 and 2004-2005 seasons. Analyses were conducted for all ages combined and for three separate age subgroups: 5 to 8 years; 9 to 17 years; and 18 to 49 years. Researchers analyzed rates of adverse events leading to visits to healthcare providers, emergency room use, or hospitalizations through a review of medical utilization data on the vaccine recipients. The rates of events within the risk period (0 to 3 or 0 to 21 days after vaccination, depending on the event) were then compared to a corresponding reference control time period.

FluMist is currently indicated for active immunization for the prevention of disease caused by influenza A and B viruses in healthy children and adolescents, 5 to 17 years of age, and healthy adults, 18 to 49 years of age. There are risks associated with all vaccines, including FluMist. As with any vaccine, FluMist does not protect 100 percent of individuals vaccinated and may not protect against viral strains not contained in the vaccine.

Under no circumstances should FluMist be administered as an injection (i.e., parenterally). FluMist is contraindicated in persons with hypersensitivity to any component of the vaccine, including eggs; in children and adolescents receiving aspirin therapy or aspirin-containing therapy; in individuals with a history of Guillain-Barre syndrome; and in individuals with known or suspected immune deficiency. The safety and efficacy of FluMist have not been established in pregnant women or for patients with chronic underlying medical conditions, including asthma or reactive airways disease; the vaccine should not be administered to these patients.

In randomized, placebo-controlled clinical trials of FluMist in its refrigerated and frozen formulations, the most common solicited adverse events in the indicated population (n=11,604) included runny nose/nasal congestion, sore throat, cough, irritability, headache, chills, vomiting, muscle aches, decreased appetite, abdominal pain, and decreased activity/feeling of tiredness/weakness.

Please see the Prescribing Information for the currently available formulation of FluMist at http://www.flumist.com/pdf/prescribinginfo.pdf, visit www.flumist.com, or call 1-877-633-4411 for additional information.

On January 5, 2007, the FDA approved MedImmune's supplemental Biologics Licensing Application (sBLA) for a refrigerated version of FluMist, which will be manufactured for the 2007-2008 influenza season. Prior versions required frozen storage. Due to the seasonal nature of influenza vaccine, full prescribing information for the refrigerated version does not yet contain complete details on vaccine strains to be included for next season's vaccine. However, preliminary prescribing information can be found at http://www.fda.gov/cber/label/inflmed010507LB.pdf.