ROTARIX Rx

Efficacy was evaluated using the reconstituted lyophilized formulation. These data are relevant to the liquid formulation because both formulations contain the same live, attenuated rotavirus strain and are manufactured using a similar process.

Efficacy Studies

Study 5

• The randomized, double-blind, placebo-controlled study was conducted in 6 European countries which included 3994 healthy infants who received a 2-dose series of Rotarix (n=2646) or placebo (n=1348). The first dose was administered from 6 to 14 weeks of age then the second dose was administered at least 4 weeks after. The 2-dose series was completed by 24 weeks of age.

• The primary endpoint was prevention of any grade of severity of rotavirus gastroenteritis caused by naturally occurring rotavirus from 2 weeks after the second dose through one rotavirus season (according to protocol, ATP). Analyses were also done to evaluate the efficacy of Rotarix against rotavirus gastroenteritis among infants who received at least one vaccination (total vaccinated cohort, TVC).

• The vaccine efficacy of Rotarix was 87.1% (95% CI, 79.6-92.1) against any grade of severity of rotavirus gastroenteritis through one rotavirus season. The TVC efficacy was 87.3% (95% CI, 80.3-92.0).

• The vaccine efficacy of Rotarix was 95.8% (95% CI, 89.6-98.7) against severe rotavirus gastroenteritis through one rotavirus season. The TVC efficacy was 96.0% (95% CI, 90.2-98.8).

• The protective effect of Rotarix against any grade of severity of rotavirus gastroenteritis observed immediately following Dose 1 administration and prior to Dose 2 was 89.8% (95% CI, 8.9-99.8).

• 100% (95% CI, 81.8-100) vaccine efficacy of Rotarix in reducing hospitalizations for rotavirus gastroenteritis through one rotavirus season. The TVC efficacy was 100% (95% CI, 81.7-100). Rotarix reduced hospitalizations for all-cause gastroenteritis regardless of presumed etiology by 74.7% (95% CI, 45.5-88.9).

Study 8

• The randomized, double-blind, placebo-controlled study was conducted in 11 countries in Latin America and Finland which included 63,225 healthy infants who received a 2-dose series of Rotarix (n=10,159) or placebo (n=10,010). The first dose was administered from 6 to 13 weeks of age then the second dose was administered at least 4 weeks after. The 2-dose series was completed by 24 weeks of age.

• The primary endpoint was prevention of severe rotavirus gastroenteritis caused by naturally occurring rotavirus from 2 weeks after the second dose through one year (ATP). Analyses were done to evaluate the efficacy of Rotarix against severe rotavirus gastroenteritis among infants who received at least one vaccination (TVC).

• The vaccine efficacy of Rotarix was 84.7% (95% CI, 71.7-92.4) against severe rotavirus gastroenteritis through 1 year. The TVC efficacy was 81.1% (95% CI, 68.5-89.3).

• The vaccine efficacy of Rotarix was 85.0% (95% CI, 69.6-93.5) in reducing hospitalizations for rotavirus gastroenteritis through 1 year. The TVC efficacy was 80.8% (95% CI, 65.7-90.0).

Efficacy through Two Rotavirus Seasons

Study 5

• The vaccine efficacy of Rotarix was the following:

• 78.9% (95% CI, 72.7-83.8) against any grade of severity of rotavirus gastroenteritis through 2 rotavirus seasons.

• 71.9% (95% CI, 61.2-79.8) in preventing any grade of severity of rotavirus gastroenteritis cases occurring only during the second season post-vaccination.

• 90.4% (95% CI, 85.1-94.1) against severe rotavirus gastroenteritis through 2 rotavirus seasons.

• 85.6% (95% CI, 75.8-91.9) in preventing severe rotavirus gastroenteritis cases occurring only during the second season post-vaccination.

• 96.0% (95% CI, 83.8-99.5) in reducing hospitalizations for rotavirus gastroenteritis through 2 rotavirus seasons.

Study 8

• The vaccine efficacy of Rotarix was the following:

• 80.5% (95% CI, 71.3-87.1) against severe rotavirus gastroenteritis through 2 rotavirus seasons.

• 79.0% (95% CI, 66.4-87.4) in preventing severe rotavirus gastroenteritis cases occurring only during the second season post-vaccination.

• 83.0% (95% CI, 73.1-89.7) in reducing hospitalizations for rotavirus gastroenteritis through 2 rotavirus seasons.

Efficacy against Specific Rotavirus Types

• Rotarix achieved statistically significant type-specific efficacy through one year against any grade of severity and severe rotavirus gastroenteritis caused by G1P[8], G3P[8], G4P[8], G9P[8], and combined non-G1 (G2, G3, G4, G9) types. 

• Rotarix achieved statistically significant type-specific efficacy through 2 years against any grade of severity and severe rotavirus gastroenteritis caused by G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and combined non-G1 (G2, G3, G4, G9) types.

Immunogenicity

Studies 5 and 8

• In Study 5, 1 to 2 months after a 2-dose series, 86.5% of 787 recipients of Rotarix reconstituted  lyophilized formulation seroconverted vs 6.7% of 420 placebo recipients.

• In Study 8, 1 to 2 months after a 2-dose series, 76.8% of 393 recipients of ROTARIX reconstituted lyophilized formulation seroconverted compared with 9.7% of 341 placebo recipients, respectively.

Study 9

• The study compared seroconversion rates and Geometric Mean Concentraions (GMCs) after administration of Rotarix liquid formulation (n=984) or the Rotarix reconstituted lyophilized formulation (n=329).

• According to primary analyses, the liquid formulation achieved noninferiority to the reconstituted lyophilized formulation for IgA seroconversion rates and GMCs at 1 to 2 months post-vaccination.

Study 10

• This study found that the liquid formulation achieved comparable anti-rotavirus IgA antibodies (concentration ≥20 U/mL) to the reconstituted lyophilized formulation 3 months after a 2-dose series.

Concomitant Vaccine Administration

Study 18

• The US concomitant vaccine administration study found that there was no evidence of interference in the immune responses to any of the antigens when Rotarix was administered with Pediarix, a US-licensed 7-valent pneumococcal conjugate vaccine, and a US-licensed Haemophilus b conjugate vaccine compared with administering Rotarix separately.

Study 10

• The concomitant administration of Rotarix liquid formulation was noninferior to Rotarix reconstituted lyophilized formulation when administered with Pediarix, Hiberix, and a US-licensed 13-valent pneumococcal vaccine regarding the immune response to each of the antigens.