Fluarix Quadrivalent

Efficacy against Influenza

The efficacy experience with Fluarix is relevant to Fluarix Quadrivalent.

• Fluarix was approved based on a randomized, double-blind, placebo-controlled trial conducted in 2 European countries during the 2006-2007 influenza season.

• Efficacy of Fluarix, containing A/New Caledonia/20/1999 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 influenza virus strains, was defined as the prevention of culture-confirmed influenza A and/or B cases, for vaccine antigenically matched strains, compared with placebo.

• Patients 18 through 64 years of age were randomly assigned 2:1 to receive Fluarix or placebo and monitored for influenza-like illnesses starting 2 weeks post-vaccination and lasting for approximately 7 months.

• The vaccine efficacy for Fluarix (trivalent formulation) was 66.9% for antigenically matched strains, and 61.6% for all culture-confirmed influenza (matched, unmatched, and untyped).

• In a post-hoc exploratory analysis, the vaccine efficacy was 73.4% in patients 18 through 49 years. The vaccine efficacy was 13.8% in patients 50 to 64 years of age. The clinical significance of these results is unknown as the trial lacked statistical power.

The efficacy of Fluarix Quadrivalent was evaluated in Trial 7, a randomized, observer-blind, non-influenza vaccine-controlled trial in patients 6 through 35 months of age. 

• Patients were randomly assigned to receive Fluarix Quadrivalent or a non-influenza control vaccine. Efficacy of Fluarix Quadrivalent was assessed for the prevention of reverse transcriptase polymerase chain reaction (RT-PCR)-confirmed influenza°A and/or B°disease, due to any seasonal influenza strain, compared with non-influenza control vaccines. 

• Influenza disease included episodes of influenza-like illness (ILI, i.e., fever ≥100.4°F with any of the following: cough, runny nose, nasal congestion, or breathing difficulty) or a consequence of influenza virus infection (acute otitis media or lower respiratory illnesses).

• The vaccine efficacy against RT-PCR-confirmed influenza associated with adverse outcomes was 64.6% (97.5% CI 53.2%, 73.5%).

• The vaccine efficacy against RT-PCR-confirmed influenza associated with adverse outcomes due to A/H1N1, A/H3N2, B/Victoria, and B/Yamagata was 71.4% (95% CI 48.5%, 85.2%), 51.3% (95% CI 32.7%, 65.2%), 86.7% (95% CI 52.8%, 97.9%), and 68.9% (95% CI 50.6%, 81.2%), respectively.

Immunological Evaluation of Fluarix Quadrivalent in Adults

• Trial 1 was a randomized, double-blind (2 arms) and open-label (one arm), active-controlled, safety, immunogenicity, and non-inferiority trial.

• Patients 18 years of age and older received Fluarix Quadrivalent (n = 1,809) or one of 2 formulations of comparator trivalent influenza vaccine (FLUARIX, TIV-1, n = 608 or TIV-2, n = 534), each containing an influenza type B virus that corresponded to one of the 2 type B viruses in Fluarix Quadrivalent (a type B virus of the Victoria lineage or a type B virus of the Yamagata lineage).

• The immunogenicity endpoints were GMTs of serum HI antibodies 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 antibody titer over baseline to ≥1:40 following vaccination, performed on the According-to-Protocol (ATP) cohort for whom immunogenicity assay results were available after vaccination.

• Fluarix Quadrivalent achieved noninferiority to both TIVs based on adjusted GMTs and seroconversion rates.

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

Immunological Evaluation of Fluarix Quadrivalent in Children

Trial 7  

• The randomized, observer-blind, non-influenza vaccine-controlled trial evaluated the efficacy of Fluarix Quadrivalent in patients 6 through 35 months of age.

• Patients received Fluarix Quadrivalent or a non-influenza control vaccine. Immune responses to each of the vaccine antigens were evaluated in sera 28 days following 1 or 2 doses in a subgroup of patients. Immunogenicity endpoints (GMTs and the percentage of subjects who achieved seroconversion) were analyzed based on the ATP cohort for whom immunogenicity assay results were available after vaccination.

• The following immune responses were observed to each antigen for Fluarix Quadrivalent 28 days after last vaccination vs the non-influenza active comparator, respectively:

• GMT for A (H1N1): 165.3 vs 12.6

• GMT for A (H3N2): 132.1 vs 14.7

• GMT for B (Victoria lineage): 92.6 vs 9.2

• GMT for B (Yamagata lineage): 121.4 vs 7.6

• Seroconversion for A (H1N1): 80.2% vs 3.5%

• Seroconversion for A (H3N2): 68.8% vs 4.2%

• Seroconversion for B (Victoria lineage): 69.3% vs 0.9%

• Seroconversion for B (Yamagata lineage): 81.2% vs 2.3%

Trial 2

• The randomized, double-blind, active-controlled trial evaluated the safety, immunogenicity, and noninferiority of Fluarix Quadrivalent in children aged 3 to 17 years. Patients received Fluarix Quadrivalent or 1 or 2 formulations of comparator trivalent influenza vaccine (Fluarix TIV-1; or TIV-2), each containing an influenza type B virus that corresponded to one of the 2 type B viruses in Fluarix Quadrivalent.

• 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 for whom immunogenicity assay results were available after vaccination.

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