Regulatory Decision Summary for Prevnar 20

The purpose of this Supplemental New Drug Submission is to seek extension of the pediatric indication of Prevnar 20 to include infants, children and adolescents from 6 weeks to less than 18 years of age.

The proposed indication of Prevnar 20 is as follows: Active immunization of infants, children and adolescents from 6 weeks through 17 years of age (prior to the 18^th birthday) for the prevention of invasive disease (including sepsis, meningitis, bacteremic pneumonia, pleural empyema and bacteremia) caused by Streptococcus pneumoniae serotypes (1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F and 33F).

The clinical program to support Prevnar 20 licensure in children 6 weeks through 17 years of age included results from one Phase 2 (B7471003) and four Phase 3 (B7471012, B7471011, B7471013 and B7471014) studies which enrolled over 5,156 infants and 831 children. The Phase 3 program was comprehensive; clinical studies targeted diverse pediatric population across different races and ethnicities who would benefit from prevention through vaccination and for whom vaccination is indicated.

The pivotal immunogenicity data are from study B7471012, a trial conducted in infants vaccinated with a 3-dose (2 infant doses and a toddler dose) series. This trial incorporated vaccination windows that span schedules of vaccine administration at 2, 4, and 11 months of age and at 3, 5, and 12 months of age. The immune responses to the 13 matched serotypes were comparable to Prevnar 13 after the 3-dose vaccination series.

Pivotal immunogenicity data in infants vaccinated with a 4-dose (3 infant doses and a toddler dose) series come from the B7471011 trial. In this trial, vaccines were administered at approximately 2, 4, 6, and 12-15 months of age. The immune responses to the 13 matched serotypes were comparable to Prevnar 13 after the 4-dose vaccination series. IgG and opsonophagocytic antibody (OPA) responses to all 7 additional serotypes after the last infant dose and the toddler dose in the Prevnar 20 group were quite higher than the responses to the corresponding serotypes in the Prevnar 13 group.

Data from infants vaccinated on a 4-dose (3 infant doses and a toddler dose) schedule were also provided from safety and immunogenicity Phase 2 trial B7471003 and Phase 3 safety trial B7471013.

B7471013 also included safety data in a subgroup of preterm infants born at ≥34 to <37 weeks gestational age.

B7471014 provided safety and immunogenicity data in children ≥15 months to <5 years of age with at least 3 prior doses of Prevnar 13 and children ≥5 to <18 years of age, who all received a single dose of Prevnar 20.

Subjects received other pediatric vaccines concomitantly. Immune responses at 30 days post dose 3 were numerically similar for recipients completing the vaccination series with Prevnar 20 compared to recipients who received a complete series with Prevnar 13. There was no evidence that Prevnar 20, as compared to Prevnar 13, interfered with the immune responses to the concomitantly administered vaccines.

Overall, 3,664 subjects received at least one dose of Prevnar 20, and 2,323 subjects received at least one dose of Prevnar 13 in the studies included in the integrated safety data.

Safety data from the eight clinical studies demonstrated an acceptable safety profile for Prevnar 20.

In healthy infants receiving 3 or 4 doses of Prevnar 20 as part of a routine vaccination schedule, the most frequently reported adverse events (AE) following each dose were reactogenicity events that are consistent with the known safety profile of pneumococcal vaccines. Safety and tolerability of Prevnar 20 appeared comparable to Prevnar 13. Slightly higher rates of solicited injection site and systemic adverse events were noted in the Prevnar 20 group than in the Prevnar 13 group, which is expected with the higher number of serotypes in the vaccine.

There were no serious adverse events (SAEs) and no deaths considered causally related to Prevnar 20.

In conclusion, the benefit risk assessment for Prevnar 20 is favorable and supports the use of Prevnar 20 in subjects aged from 6 weeks through 17 years.