Regulatory Decision Summary for Vaxneuvance

Eight studies were submitted to support the safety and immunogenicity of Vaxneuvance (V114):

one Phase 2 (V114-008) and seven Phase 3 (V114-023, V114-024, V114-025, V114-027, V114-029, V114-030, V114-031) studies, which provided the main data to support the effectiveness and safety of Vaxneuvance in children, including pre-term infants, catch-up vaccination, children with sickle-cell disease (SCD), HIV-infected children.

Studies V114-025, V114-029, V114-027, and V114-008 evaluated the safety and immunogenicity in healthy infants including preterm infants. Subjects received other pediatric vaccines concomitantly. Immune responses at 30 days postdose 3 were numerically similar for recipients completing the vaccination series with Vaxneuvance compared to recipients who received a complete series with Prevnar 13. There was no evidence that Vaxneuvance, as compared to Prevnar 13, interfered with the immune responses to the concomitantly administered vaccines.

Study V114-024 was submitted to support a recommendation for Vaxneuvance catch-up vaccination in healthy children, 7 months to 17 years of age, who are delayed in receiving pneumococcal vaccine (PCV) immunization per the recommended schedule. Catch-up vaccination with Vaxneuvance elicited immune responses that were numerically similar to Prevnar 13 for the shared serotypes and higher than Prevnar 13 for the unique serotypes 22F and 33F contained in Vaxneuvance.

Study V114-023 evaluated the safety and immunogenicity of Vaxneuvance compared to Prevnar 13 in 104 children 5 to 17 years of age (inclusive) with sickle- cell disease (SCD) who were either pneumococcal vaccine (PCV) naïve or had a history of previous immunization with a lower-valent PCV. Immune responses were numerically similar between the two vaccination groups for the 13 shared serotypes and higher in Vaxneuvance for serotypes 22F and 33F.

Study V114-030 demonstrated that Vaxneuvance was immunogenic in HIV-infected in children 6 to 17 years of age (inclusive)

Study V114-031 was submitted to support that vaccination with Vaxneuvance to healthy full-term and preterm infants (approximately 2 months [42 to 90 days] of age) elicited immune responses that were generally comparable to Prevnar 13 for the 13 shared serotypes and higher for the 2 serotypes unique to Vaxneuvance.

Overall, 5,366 subjects received at least one dose of Vaxneuvance and 3,491 subjects received at least one dose of Prevnar 13 in the studies included in the integrated safety data. A total of 221 preterm infants (<37 weeks gestational age at birth) received at least 1 dose of Vaxneuvance and 234 preterm infants received at least 1 dose of Prevnar 13.

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

In healthy infants receiving 3 or 4 doses of Vaxneuvance as part of a routine vaccination schedule, and in children from 2 through 17 years of age receiving a catch-up 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 Vaxneuvance appeared comparable to Prevnar 13. Slightly higher rates of solicited injection site and systemic adverse events were noted in the Vaxneuvance group than in the Prevnar 13 group, which is expected with the higher number of serotypes in the vaccine.

No unique safety concerns were observed with Vaxneuvance when administered to children with SCD or HIV relative to healthy children of a similar age.

There were no serious adverse events (SAE) and no deaths considered causally related to Vaxneuvance.

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