V114 pneumococcal vaccine noninferior to PCV13 in adults, phase 3 studies show
Merck’s investigational V114 pneumococcal conjugate vaccine — which includes 15 serotypes — is noninferior to the 13-valent pneumococcal conjugate vaccine currently on the market for adults, the company announced in a press release.
“Diseases caused by serotypes not covered by the currently available pneumococcal conjugate vaccine are increasing worldwide and can vary by country or region. Additionally, we continue to see pneumococcal disease caused by serotypes included in the existing pneumococcal vaccines,” Roy Baynes, MD, PhD, senior vice president, head of global clinical development and chief medical officer of Merck Research Laboratories, said in the press release. “Continued scientific innovation in pneumococcal disease prevention is needed to target the serotypes that pose the greatest risk to specific populations while maintaining immune response as new serotypes are added. These phase 3 data demonstrated that V114 generated a robust immune response to all 15 serotypes included in the vaccine and reinforce the potential for this investigational vaccine to help protect adults against pneumococcal disease.”
Results from the phase 3 PNEU-AGE trial, a multicenter, double-blind, randomized study of V114 in adults aged 50 years and older, showed that V114 was noninferior to the 13-valent pneumococcal conjugate vaccine (PCV13) for 13 shared serotypes. Additionally, V114 was superior to PCV13 for serotypes 33F and 22F. V114 also showed superiority to PCV13 for serotype 3 during a secondary immunogenicity analysis.
In the phase 3 PNEU-TRUE trial — which also included adults aged 50 years or older — V114 met its primary immunogenicity endpoint demonstrating equivalent immune response across all 15 serotypes.
In both studies, V114 was generally well tolerated and had a safety profile comparable to PCV13.
“All things being equal (ie, not more expensive than and similar side effects to PCV13), then if the product is licensed, it might be appropriate to use in the target population,” Eugene Shapiro, MD, Infectious Disease News Editorial Board Member and professor of pediatrics and epidemiology at Yale School of Public Health, told Healio. “However, the [Advisory Committee on Immunization Practices] changed the recommendation to routinely administer PCV13 to adults 65 years and older (they recommend shared decision-making about giving and getting the vaccine), largely because routine administration of PCV13 to children nearly eliminated invasive disease due to vaccine serotypes in adults. Furthermore, another manufacturer is also far along in development of a pneumococcal conjugate vaccine that contains 20 different serotypes.”
Shapiro noted that serotype replacement is a potential concern that will need to be addressed in future research.
“A major issue is whether there will be significant ‘serotype replacement’ in adults — that is, giving the vaccine just to children markedly reduces both colonization and invasive disease due to vaccine types in both children and adults,” Shapiro said. “However, colonization is replaced by nonvaccine types in children and ultimately in adults. These ‘replacement’ types overall may be less likely to cause disease in children but do cause a significant amount of disease in adults in many countries. For reasons that are not well understood, this has not yet been a major problem in the United States. More research in this area is needed. And of course, a ‘universal’ vaccine that is effective against all of the approximately 95 different serotypes of pneumococci would be ideal.”
According to Merck, V114 is also being tested in children and those who are immunocompromised. Its phase 3 clinical development program includes 16 trials investigating the vaccine’s safety, tolerability and immunogenicity.