Pivotal Trial Evaluating Use of Pneumococcal 15-Valent Conjugate Vaccine in Infants Meets Key Immunogenicity, Safety Endpoints

At 30 days following the third dose in the series, the pneumococcal 15-valent conjugate vaccine was non-inferior to the 13-valent vaccine for all 13 shared serotypes.

The phase 3 pivotal PNEU-PED trial evaluating the use of the pneumococcal 15-valent conjugate vaccine (Vaxneuvance; Merck) in infants met key immunogenicity and safety endpoints, according to a company press release.

The trial is evaluating the immunogenicity, safety, and tolerability of the vaccine in healthy infants enrolled between 42 and 90 days of age. Patients were given a 4-dose regimen of either Vaxneuvance or the licensed 13-valent pneumococcal conjugate vaccine (PCV13) at 2, 4, 6, and 12 to 15 months of age.

Pneumococcal bacteria can impact children differently than adults, with more than 100 different types of bacteria. Children under 2 years of age are particularly vulnerable to pneumococcal infection and incidence of invasive pneumococcal disease remains highest in the first year of life. Certain serotypes continue to put children at risk, including serotypes 22F, 33F, and 3, which are found in more than 25% of all cases of invasive pneumococcal disease in children younger than 5 years of age.

“By nature, pneumococcal disease is constantly evolving,” said Roy Baynes, MD, PhD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, in the press release. “Strains of the disease associated with invasiveness cause significant disease burden in children, calling for innovation to help protect this vulnerable population worldwide. With the inclusion of serotypes 22F and 33F, Vaxneuvance has the potential to play an important role in the prevention of invasive pneumococcal disease in children.”

According to the press release, the vaccine had a safety profile generally comparable to PCV13 following receipt of any vaccine dose. At 30 days following the third dose in the series, the vaccine was non-inferior to PCV13 for all 13 shared serotypes based on serotype-specific response rates, and for 12 of the 13 shared serotypes based on serotype-specific immunoglobulin G (IgG) geometric mean concentrations.

The lower bounds of the 2-sided 95% confidence intervals for the serotype-specific IgG GMC ratios were greater than 0.5 for 12 shared serotypes. Specifically, the lower bound was 0.48 for serotype 6A, which narrowly avoids non-inferiority criteria. At 30 days following the fourth dose, the vaccine was non-inferior to PCV13 for all 13 shared serotypes based on serotype-specific IgG geometric mean concentrations.

Secondary endpoints also demonstrated statistically superior immune responses for Vaxneuvance in comparison to PCV13 for shared serotype 3 and unique serotypes 22F and 33F based on prespecified criteria, in addition to non-inferior immune responses to antigens contained in several routinely used pediatric vaccines when administered concomitantly with Vaxneuvance or PCV13.

The PNEU-LINK trial is a second phase 3 study evaluating the safety and tolerability of Vaxneuvance in healthy infants. In that trial, researchers found that it was generally well-tolerated with a safety profile generally comparable to PCV13 in healthy infants enrolled at 42 to 90 days of age. Full results from both studies will be presented at an upcoming scientific meeting, according to the press release.

The Vaxneuvance phase 3 clinical development program includes 16 trials investigating the safety, tolerability, and immunogenicity of Vaxneuvance in a variety of populations at high risk for pneumococcal disease, including 10 investigating its use in infants and children. In July 2021, the FDA approved the vaccine for adults 18 years of age and older for active immunization for the prevention of invasive disease caused by the 15 S. pneumoniae serotypes contained in the vaccine.

REFERENCE

Merck Announces Vaxneuvance (Pneumococcal 15-valent Conjugate Vaccine) Met Key Immunogenicity and Safety Endpoints in Phase 3 Pivotal Trial Evaluating Use in Infants, PNEU-PED (V114-029). News release. Merck; August 25, 2021. Accessed August 25, 2021. https://www.merck.com/news/merck-announces-vaxneuvance-pneumococcal-15-valent-conjugate-vaccine-met-key-immunogenicity-and-safety-endpoints-in-phase-3-pivotal-trial-evaluating-use-in-infants-pneu-ped-v114-029/