FDA Approves Expanded Indication for Merck’s Pneumococcal Vaccine for Infants and Children

The Food and Drug Administration (FDA) approved the pneumococcal 15-valent conjugate vaccine (Vaxneuvance) for the use in infants 6 weeks old through 17 years of age for pneumococcal disease. This Merck vaccine is indicated to provide protection against Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F.

This expanded indication comes nearly a year after the vaccine was approved in adults ≥18 years old.

“Despite decreases in incidence of invasive pneumococcal disease in children, certain key serotypes continue to cause serious illness that can lead to death in children under the age of 5, with serotypes 3, 22F and 33F responsible for more than a quarter of all invasive pneumococcal disease cases in this population,” Steven Shapiro, MD, chairman, department of pediatrics, Jefferson Abington Hospital, and investigator for the PNEU-PED trial, said in a statement. “With the robust clinical data supporting Vaxneuvance and this FDA approval, Vaxneuvance will be an important new option to help advance protection for children.”

The vaccine dosage is for 0.5 mL, and given as 4-dose series given at 2, 4, 6, and 12 through 15 months of age. The Vaxneuvance vaccine can also be administered as a single dose in children and adolescents 2 through 17 years of age who have received an incomplete series of another pneumococcal conjugate vaccine.

Data

The FDA’s approval was based on data from seven randomized, double-blind clinical studies assessing safety, tolerability and immunogenicity of the vaccine in infants, children and adolescents Clinical data from the pivotal study showed that immune responses elicited by Vaxneuvance following a four-dose pediatric series were non-inferior to the currently available 13-valent pneumococcal conjugate vaccine (PCV13) for the 13 shared serotypes based on serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs).

The company offered more insights into their studies, including:

Children receiving a four-dose series. The phase 3, multicenter, randomized, double-blind, active comparator-controlled study evaluated the safety, tolerability and immunogenicity of a 4-dose series of Vaxneuvance in healthy infants (n=1720) (V114-029/PNEU-PED [NCT03893448]). In the study, participants were randomized one-to-one to receive a four-dose series of Vaxneuvance or PCV13 at 2, 4, 6, and 12-15 months of age.

The assessed immune responses included serotype specific IgG response rates against capsular polysaccharides of S. pneumoniae at 30 days post-dose 3 (PD3) and IgG geometric mean concentrations (GMCs) at 30 days PD3 and post-dose 4 (PD4). Additionally, antibody responses to other routine licensed pediatric vaccines were evaluated when administered concomitantly with Vaxneuvance or PCV13.

Vaxneuvance elicited immune responses for all 15 serotypes contained in the vaccine. Based on serotype-specific IgG GMCs, at 30 days PD4, Vaxneuvance was non-inferior to PCV13 for all 13 shared serotypes and the two serotypes unique to Vaxneuvance, 22F and 33F. Serotypes 22F and 33F were compared with serotype 4, which had the lowest IgG GMC of all shared serotypes in PCV13, excluding serotype 3. Results of the secondary analysis showed superior immune responses for the vaccine in comparison to PCV13 for serotypes 3, 22F and 33F.

PCV interchangeability. A phase 3, randomized, double-blind, active comparator-controlled, descriptive study evaluated the interchangeability of Vaxneuvance and PCV13 with respect to safety, tolerability and immunogenicity in healthy infants (n=900) (V114-027/PNEU-DIRECTION [NCT03620162]). The study demonstrated generally comparable immune responses for participants completing the vaccination series with Vaxneuvance compared to those who completed series with PCV13, for the 13 shared serotypes. The safety profile observed when the vaccine was used to complete a four-dose pneumococcal conjugate vaccine series initiated with PCV13 was similar to the safety profile following a complete 4-dose regimen of either Vaxneuvance or PCV13.

Use as part of a catch-up series. A phase 3, randomized, double-blind, active comparator-controlled, descriptive study evaluated the safety, tolerability and immunogenicity of catch-up vaccination regimens of Vaxneuvance in healthy infants, children and adolescents 7 months to 17 years of age (n=606) (V114-024/PNEU-PLAN [NCT03885934]). The study demonstrated generally comparable immune responses after receipt of the last dose for the 13 serotypes targeted by Vaxneuvance and PCV13, and higher immune responses for the two serotypes unique to Vaxneuvance, 22F and 33F.

Next Steps

The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) is meeting today to discuss and make recommendations on the use of the vaccine in pediatric populations.