Merck's 15-Valent Pneumococcal Conjugate Vaccine V114 Meets Primary Immunogenicity and Safety Endpoints in Two Phase 3 Pediatric Studies

May 21, 2021 /BioonBIOON/ --Merck & Co. recently announced,15-Valent Pneumococcal Conjugate Vaccine V114 (15-Valent)In the two Phase 3 trials within the Phase 3 pediatric clinical programMet the primary immunogenicity and safety endpoints。

These data support the potential use of V114 in healthy infants, including: (1) infants who may have previously initiated vaccination with the currently available 13-valent pneumococcal conjugate vaccine (PCV13) (PNEU-DIRECTION trial); (2) infants who are pneumococcal vaccine-naive or who have previously received a complete or partial immunization regimen with lower-valent pediatric pneumococcal conjugate vaccine (PCV) (PNEU-PLAN trial).

Pneumococcal vaccine (Image source: firstcry.com)

The PNEU-DIRECTION (V114-027) interchangeability study is a Phase 3, multicenter, randomized, double-blind study conducted in healthy infants aged 42 to 90 days (n=900) to evaluate the interchangeability of V114 and PCV13 in terms of safety, tolerability, and immunogenicity. In the study, these infants were randomized to one of five vaccination groups, receiving: a complete 4-dose PCV13 regimen, one of three mixed 4-dose regimens followed by V114, or a complete 4-dose V114 regimen. Results showed that,Infants receiving the 4-dose PCV13 series elicited comparable immune responses against the 13 serotypes or pneumococcal strains covered by both vaccines compared with infants receiving a mixed-dose PCV13 schedule followed by V114.

The PNEU-PLAN (V114-024) catch-up study is a Phase 3, multicenter, randomized, double-blind, active-controlled, descriptive study conducted in healthy infants, children, and adolescents aged 7 months to 17 years (n=606) evaluating the safety, tolerability, and immunogenicity of the V114 catch-up vaccination regimen. Subjects were either pneumococcal vaccine-naïve or had previously received a partial or complete schedule of a licensed pediatric PCV. In the study, subjects received a 3-dose (7–11 months), 2-dose (12–23 months), or 1-dose (2–17 years) regimen of V114 based on their age at randomization. Results showed that,When V114 was administered as a catch-up regimen to healthy children aged 7 months through 17 years, the immune responses against the 13 shared serotypes were comparable to those of PCV13. For the two serotypes (22F and 33F) included in V114 but not in PCV13, immunogenicity was higher in the V114 group than in the PCV13 group.

In each study, V114 was generally well tolerated, with a safety profile comparable to that of PCV13.The full results of the PNEU-DIRECTION and PNEU-PLAN studies will be presented at future scientific conferences.

Dr. Roy Baynes, Chief Medical Officer, Head of Global Clinical Development, and Senior Vice President at MSD Research Laboratories, stated: “Although pneumococcal conjugate vaccination has had a positive impact on pediatric case numbers, pneumococcal disease continues to cause severe illness and death in children under 5 years of age globally. MSD aims to expand coverage to new serotypes not covered by currently available pediatric pneumococcal conjugate vaccines, while maintaining a robust immune response to the serotypes in existing vaccines, to help sustain the progress achieved to date. The results of these studies support the potential of V114 to elicit immunogenicity to PCV13 serotypes in infants who have previously received one or more doses of PCV13, as well as the potential to elicit immunogenicity to the 15 serotypes in V114 in a catch-up setting.”

Pneumococcal pneumonia (Image source: bigstockphoto.com)

Globally, the incidence of pneumococcal disease is on the rise, partly driven by pathogenic serotypes not covered by currently available pneumococcal conjugate vaccines. There are 100 different types of pneumococci, which affect children differently than adults. Children under 2 years of age are particularly susceptible to pneumococcal infection, and the incidence of invasive pneumococcal disease remains highest during the first year of life. Certain pneumococcal serotypes continue to place children at risk, including serotypes 22F and 33F, which account for 16% of all invasive pneumococcal disease cases in children under 5 years of age.

V114 is an investigational 15-valent vaccine, comprising pneumococcal polysaccharides from 15 serotypes and CRM197`Carrier`conjugated to a carrier protein, including serotypes 22F and 33F, these two serotypes are commonly associated with invasive pneumococcal disease worldwide, but are not included in currently licensed pneumococcal conjugate vaccines for adults.

V114 is in Phase III clinical development for the prevention of pneumococcal disease in adults and children. In January 2019, the United StatesFDAV114 has been granted Breakthrough Therapy Designation (BTD) for the prevention of invasive pneumococcal disease (IPD) caused by the vaccine serotypes in infants and pediatric patients aged 6 weeks through 18 years.

The Phase III clinical development program for V114 consists of 16Clinical TrialThe study population comprised [subjects], and the safety, tolerability, and immunogenicity of V1114 were evaluated in different populations (including healthy elderly individuals, healthy children, immunocompromised individuals, and patients with certain chronic diseases).

Currently, V114 is under review by the U.S. FDA and the European Medicines Agency (EMA): for the prevention of invasive pneumococcal disease in adults aged 18 years and older. In the U.S.,FDAA review decision will be issued by July 18, 2021.

Based on data from pediatric clinical programs, MSD plans to the United States by the end of the yearFDASubmit a supplemental Biologics License Application (sBLA) for the use of V114 in the pediatric population. (Bioon.com)

Original Source: Merck Announces Positive Topline Results from PNEU-DIRECTION (V114-027) and PNEU-PLAN (V114-024) Phase 3 Pediatric Studies for V114, Merck’s Investigational 15-valent Pneumococcal Conjugate Vaccine