Merck's Adult Pneumococcal Conjugate Vaccine Shows Promise in Phase 3 Trials

An investigational pneumococcal conjugate vaccine, V116, demonstrated statistically significant immune responses in both vaccine-naive adults and those previously vaccinated in 2 phase 3 trials, according to topline results released by Merck.

The 21-valent pneumococcal conjugate vaccine indicated for the prevention of invasive pneumococcal disease and pneumococcal pneumonia, specifically designed for adults, had a comparable safety profile to the comparator vaccines and includes 8 Streptococcus pneumoniae serotypes associated with approximately 30% of cases of invasive pneumococcal disease in people 65 and older that are not currently covered by approved pneumococcal vaccines. The vaccines can help prevent meningitis, bacteremia, and pneumonia, as well as other types of infections caused by Streptococcus pneumoniae.

“These results support the potential for V116 to become an important new preventative option for adults, regardless of prior pneumococcal vaccination status," said Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories.

There are currently 3 licensed pneumococcal conjugate vaccines: PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F); PCV15 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F); and PCV20 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F); as well as 1 pneumococcal polysaccharide vaccine, PPSV23 (serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F).

V116 is being investigated in the phase 3 STRIDE-3 and STRIDE-6 clinical trials, both of which are randomized, double-blind, active comparator-controlled studies.

STRIDE-3 is assessing the safety, tolerability, and immunogenicity of V116 compared with PCV20 is pneumococcal vaccine-naive adults (N=2600). Participants received 1 dose of the study drug and the comparator, with primary end points including safety, serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) 30 days post-vaccination and percentage of participants with ≥4-fold rise from baseline in serotype-specific OPAs.

STRIDE-6 is comparing V116 in adults 50 years and older (N=717) who previously received a pneumococcal vaccine at least 1 year prior (alone or in combination), including PPSV23, PCV13, PCV15, and PCV20, or PCV13+PPSV23, PCV15+PPSV23 or PPSV23+PCV13. Participants were randomly assigned to receive 1 dose of either V116, PCV15, or PPSV23, with primary end points including safety and GMT of serotype-specific OPA responses 30 days post-vaccination.

In STRIDE-3, statistically significant immune responses to V116 were demonstrated compared with PCV20 for serotypes common to both vaccines by serotype-specific OPA 30 days post-vaccination in vaccine-naive adults, with positive immune responses also recorded for the 8 serotypes unique to V116. In STRIDE-6, V116 was immunogenic for all 21 pneumococcal serotypes in the vaccine in previously vaccinated adults.

Notably, V116 is also being examined in additional phase 3 clinical trials to assess safety and immunogenicity in special populations, including individuals with HIV (STRIDE-7; NCT05393037) and those at increased risk for pneumococcal disease, including individuals with diabetes, chronic liver disease, chronic obstructive pulmonary disease, mild or moderate persistent asthma, chronic heart disease, and/or chronic kidney disease (STRIDE-8; NCT05696080).

A recent study published in JAMA Internal Medicine examined Vaccine Adverse Event Reporting System (VAERS) events related to reports of skin necrosis at the injection site after administration of Merck's PPSV23 (Pneumovax 23). According to the investigators, the injection site necrosis reporting rate was less than 0.2 cases per million vaccine doses distributed. They also did a search of the literature which showed 2 cases of injection site necrosis after the 23-valent pneumococcal vaccine. The vaccine packaging has since been updated to reflect the safety concern of injection site necrosis. The authors concluded that the "benefit-risk balance for this vaccine remains favorable."