Merck’s 15-valent pneumococcal vaccine noninferior to PCV13

Issue: June 2019

Heather Platt

Merck announced that its investigational 15-valent pneumococcal conjugate vaccine, or V114, was noninferior in protecting against the serotypes included in Pfizer’s 13-valent vaccine in children aged 6 to 12 weeks. V114 also produced an immune response in infants for two additional serotypes that cause disease — 22F and 33F.

Perspective from William Schaffner, MD

Data on the vaccine’s safety, tolerability and immunogenicity were presented at the Annual Meeting of the European Society for Paediatric Infectious Diseases.

“While preliminary, these phase 2 data are promising,” Heather Platt, MD, a Merck senior principal scientist, told Infectious Diseases in Children. “We hope that demonstrating an immune response in these previously unaddressed serotypes, while maintaining noninferiority in the serotypes shared with PCV13, will make a compelling case for V114 as we progress toward our phase 3 trials.”

In the double-blind, randomized phase 2 trial, researchers compared two lots of V114 (n = 350 for lot one and n = 347 for lot two) to the 13-valent pneumococcal conjugate vaccine, or PCV13 (n = 347), in healthy infants at 2, 4, 6 and 12 to 15 months of age.

The percentage of infants who acheived WHO-accepted thresholds for immune response (IgG 0.35 g/mL) with either lot of V114 was noninferior to the percentage seen with PCV13 for the 13 serotypes shared between the two vaccines. Additionally, more infants vaccinated with either of the two lots of V114 achieved the threshold of immune response against serotype 3 — a significant cause of morbidity and mortality worldwide (96% and 94.1% vs. 71.8%).

According to Merck, more than 98% of infants who received V114 reached the threshold of immune response for serotype 22F (98.9% for lot one and 98.5% for lot two), and more than 87% of infants reached this threshold for serotype 33F (87.7% for lot one and 90.1% for lot two) — both of which are not included in PCV13.

Researchers observed similar adverse events after vaccination with V114 and PCV13, and the number of these events was also comparable between the two vaccines.

V114 previously received a breakthrough therapy designation from the FDA to prevent invasive pneumococcal disease (IPD) caused by vaccine serotypes in children aged 6 weeks to 18 years.

Merck is currently investigating the use of V114 in adults, pediatric patients and those who are immunocompromised and at increased risk for IPD in 11 phase 3 clinical trials. – by Katherine Bortz

Reference:

Hurtado K, et al. A phase 2, double-blind, randomized, multicenter trial to evaluate the safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) compared to PCV13 in healthy infants. Presented at: ESPID 2019; May 6-11, 2019; Ljubljana, Slovenia.

Azarian Taj, et al. PLoS Pathog. 2018;doi:10.1371/journal.ppat.1007438.

Disclosure: Infectious Diseases in Children was unable to confirm relevant financial disclosures at the time of publication.

Perspective

William Schaffner, MD

Prevention of disease is medicine's highest goal, and vaccines are an elegant and effective means of prevention. The prospect of preventing even more disease is alluring, and this report is a cause for optimism. Pneumococcal conjugate vaccines — first PCV7 and then PCV13 — have been remarkably effective in directly preventing serious invasive pneumococcal disease by vaccinating infants and young children as well as by indirectly protecting adults via “herd” effects.

Of course, there are other pneumococcal serotypes that are not included in PCV13 that continue to cause disease. The current study demonstrates that a new candidate vaccine containing two additional serotypes (22F and 33F) evoked an immune response in infants aged 6 to 12 weeks that was comparable to that of PCV13 for the 13 shared serotypes and also was immunogenic for the two additional serotypes. The safety data also were comparable.

We look forward to the results of further trials currently underway in healthy children and adults as well as in patients who are immunocompromised. When it comes to prevention, the more, the merrier!

William Schaffner, MD

Professor of preventive medicine

Vanderbilt University School of Medicine

Disclosures: Schaffner reports being a member of a data safety monitoring board for Pfizer and being a consultant to Roche Diagnostics. Until about 1 year ago, he was a member of the data safety monitoring board for Merck, which had oversight of the V114 series of vaccine trials.