FLUMIST QUADRIVALENT Rx

The clinical experience with FluMist is relevant to FluMist Quadrivalent.

Efficacy Studies of FluMist in Children and Adolescents

MI-CP111 Trial

• The multi-national, randomized, double-blind, active-controlled trial compared the efficacy of FluMist to an intramuscularlary administered, inactivated Influenza Virus Vaccine manufactured by Sanofi Pasteur Inc. (active control) in 3916 children 6 months to less than 5 years of age during the 2004-2005 influenza season. 

• The trial included children without severe asthma, without use of bronchodilator or steroids, and without wheezing within the prior 6 weeks. Patients were randomly assigned 1:1 to receive FluMist or active control. Children who previously received any influenza vaccine were given a single dose of study vaccine; and children who never previously received an influenza vaccine were given 2 doses.

• The primary endpoint was the culture-confirmed modified CDC-ILI (CDC-defined influenza-like illness), defined as a positive culture for a wild-type influenza virus associated within ±7 days of modified CDC-ILI. Modified CDC-ILI was defined as fever (temperature ≥ 100°F oral or equivalent) with cough, sore throat, or runny nose/nasal congestion on the same or consecutive days.

• Patients in the FluMist arm achieved a 44.5% (95% CI, 22.4-60.6) reduction in influenza rate compared with active control as measured by culture-confirmed modified CDC-ILI caused by wild-type strains antigenically similar to those contained in the vaccine.

D153-P501 Trial

• The randomized, double-blind, saline placebo-controlled trial evaluated the efficacy of FluMist in 3174 children 12 through 35 months of age without high-risk medical conditions against culture-confirmed influenza illness. The study was conducted in Asia over 2 successive seasons (2000-2001 and 2001-2002). Patients were randomly assigned 3:2 to receive 2 doses of study vaccine or placebo at least 28 days apart in Year 1.

• The primary endpoint of the trial was the prevention of culture-confirmed influenza illness due to antigenically matched wild-type influenza.

• During the second year of Study D153-P501, for children who received 2 doses in Year 1 and 1 dose in Year 2, FluMist demonstrated 84.3% (95% CI: 70.1, 92.4) efficacy against culture-confirmed influenza illness due to antigenically matched wild-type influenza.

Study AV006

• The second multi-center, randomized, double-blind, AF-SPG placebo-controlled trial evaluated the efficacy of FluMist against culture-confirmed influenza in children without high-risk medical conditions over 2 successive seasons (1996-1997 ad 1997-1998).

• The primary endpoint of the trial was the prevention of culture-confirmed influenza illness due to antigenically matched wild-type influenza in children who received two doses of vaccine in the first year and a single revaccination dose in the second year.

• During the second year, the primary circulating strain was the A/Sydney/05/97 H3N2 strain, which was antigenically dissimilar from the H3N2 strain represented in the vaccine, A/Wuhan/359/95; FluMist demonstrated 87.0% (95% CI: 77.0, 92.6) efficacy against culture-confirmed influenza illness.

Immune Response Study of FluMist Quadrivalent in Children and Adolescents

• The multicenter, randomized, double-blind, active-controlled, non-inferiority study (MI-CP208) compared the immunogenicity of FluMist Quadrivalent to FluMist (active control) in patients 2 to 17 years of age.

• A total of 2312 patients were randomly assigned 3:1:1 to receive either FluMist Quadrivalent or 1 of 2 formulations of comparator vaccine FluMist, each containing a B strain that corresponded to 1 of the 2 B strains in FluMist Quadrivalent (a B strain of the Yamagata lineage or a B strain of the Victoria lineage).

• Immunogenicity was evaluated by comparing the 4 strain-specific serum hemagglutination inhibition (HAI) antibody geometric mean titers (GMTs) post dosing and provided evidence that the addition of the second B strain did not result in immune interference to other strains included in the vaccine.

Effectiveness Study of FluMist in Adults

• The US multicenter, randomized, double-blind, AF-SPG placebo-controlled trial evaluated the efficacy of FluMist in adults 18 to 64 years of age without high-risk medical conditions over the 1997-1998 influenza season. Patients were randomly assigned 2:1 to receive either FluMist or placebo. The primary endpoint of the trial was the reduction in the proportion of participants with one or more episodes of any febrile illness, and prospective secondary endpoints were severe febrile illness and febrile upper respiratory illness.

• In adults 50 to 64 years of age, effectiveness for any of the 3 endpoints was not demonstrated. In adults 18 to 49 years of age, effectiveness was also not demonstrated for the primary endpoint.

• In a post-hoc analysis, effectiveness was demonstrated using an endpoint of CDC-ILI in the age group 18 through 49 years of age.

Immune Response Study of FluMist Quadrivalent in Adults

• The multicenter, randomized, double-blind, active-controlled, and non-inferiority study (MI-CP185) evaluated the safety and immunogenicity of FluMist Quadrivalent compared with those of FluMist (active control) in 1800 adults 18 to 49 years of age.

• Patients were randomly assigned 4:1:1 to receive either 1 dose of FluMist Quadrivalent or 1 dose of 1 of 2 formulations of comparator vaccine, FluMist, each containing a B strain that corresponded to one of the two B strains in FluMist Quadrivalent (a B strain of the Yamagata lineage and a B strain of the Victoria lineage). 

• The addition of the second B strain did result in immune interference to other strains included in the vaccine.