Flulaval Quadrivalent

Efficacy against Influenza

Trial 3

• The randomized, observer-blind, non-influenza vaccine-controlled trial evaluated the efficacy of Flulaval Quadrivalent during the 2010-2011 influenza season in healthy participants aged 3 to 8 years. Patients were randomly assigned 1:1 to receive either Flulaval Quadrivalent, containing H1N1, H3N2, Victoria lineage, and Yamagata lineage influenza strains, or Havrix as a control vaccine.

• Children with no history of influenza vaccination received 2 doses of Flulaval Quadrivalent or Havrix approximately 28 days apart. Children with a history of influenza vaccination received 1 dose of Flulaval Quadrivalent or Havrix.

• Efficacy of Flulaval Quadrivalent was assessed for the prevention of reverse transcriptase polymerase chain reaction (RT-PCR)-positive influenza A and/or B disease presenting as influenza-like illness (ILI).

• The vaccine efficacy for Flulaval Quadrivalent was 55.4% (95% CI, 39.1-67.3) for all RT-PCR-positive influenza.

• The vaccine efficacy for Flulaval Quadrivalent was 55.9% (95% CI, 35.4-69.9) for all culture-confirmed influenza.

• The vaccine efficacy for Flulaval Quadrivalent was 45.1% (95% CI, 9.3-66.8) for antigenically matched culture-confirmed influenza.

• In an exploratory analysis by age, the vaccine efficacy against RT-PCR-positive influenza A and/or B disease presenting as ILI was 35.3% (95% CI, -1.3, 58.6) in participants aged 3 to 4 years, and 67.7% (95% CI, 49.7, 79.2) in participants aged 5 to 8 years. The trial lacked statistical power so the clinical significance of these results is unknown.

• The risk reduction of fever >102.2°F/39.0°C associated with RT-PCR-positive influenza was 71.0% (95% CI: 44.8, 84.8) based on the ATP cohort for efficacy [Flulaval quadrivalent (n = 12/2,379); Havrix (n = 41/2,398)].

Immunological Evaluation of Flulaval Quadrivalent 

Adults – Trial 1

• The randomized, double-blind, active-controlled, safety and immunogenicity trial  evaluated Flulaval Quadrivalent in patients aged 18 years and older.

• Patients received Flulaval Quadrivalent (n = 1246) or one of 2 formulations of comparator trivalent influenza vaccine (Flulaval, TIV-1, n = 204 or TIV-2, n = 211), each containing an influenza type B virus that corresponded to one of the 2 type B viruses in Flulaval Quadrivalent (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage).

• The immunogenicity endpoints were GMTs adjusted for baseline, performed on the According-to-Protocol (ATP) cohort for whom immunogenicity assay results were available after vaccination.

• Flulaval Quadrivalent achieved noninferiority to both TIVs based on adjusted GMTs.

• The antibody response to influenza B strains contained in Flulaval Quadrivalent was higher than the antibody response after vaccination with a TIV containing an influenza B strain from a different lineage.

Children – Trial 4

• The randomized, observer-blind, active-controlled trial evaluated Flulaval Quadrivalent in participants aged 6 to 35 months.

• Patients received 0.5mL of Flulaval Quadrivalent containing 15mcg HA of each of the 4 influenza strains included in the vaccine (n=1207); or 0.25mL of control vaccine Fluzone Quadrivalent containing 7.5mcg HA of each of the 4 influenza strains included in the vaccine (n=1217).

• The immunogenicity endpoints were GMTs adjusted for baseline, and the percentage of subjects who achieved seroconversion, defined as a pre-vaccination HI titer of <1:10 with a post-vaccination titer ≥1:40 or at least a 4-fold increase in serum HI titer over baseline to ≥1:40, following vaccination, performed on the ATP cohort.

• Flulaval Quadrivalent achieved noninferiority to the comparator for all 4 vaccine strains based on adjusted GMTs and seroconversion rates.

Children – Trial 2

• The randomized, double-blind, active-controlled trial evaluated Flulaval Quadrivalent in patients aged 3 to 17 years.

• Patients received Flulaval Quadrivalent (n=878), or one of 2 formulations of a comparator trivalent influenza vaccine (Fluarix, TIV-1 [n=871] or TIV-2 [n=878]), each containing an influenza type B virus that corresponded to one of the 2 B viruses in Flulaval Quadrivalent (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage).

• The immunogenicity endpoints were GMTs adjusted for baseline, and the percentage of subjects who achieved seroconversion, defined as at least a 4-fold increase in serum HI titer over baseline to ≥1:40, following vaccination, performed on the ATP cohort.

• Flulaval Quadrivalent was noninferior to both TIVs based on adjusted GMTs and seroconversion rates. The antibody response to influenza B strains contained in Flulaval Quadrivalent was higher than the antibody response after vaccination with a TIV containing an influenza B strain from a different lineage.