Extending MenB vaccine to children under age 10 years
By Bruce Jancin
MALMO, SWEDEN – It’s full speed ahead for the use of Pfizer’s serogroup B bivalent meningococcal vaccine in 1- to 9-year-olds on the strength of reassuring immunogenicity and safety findings in two phase 2, randomized, multicenter, observer-blinded clinical trials presented at the annual meeting of the European Society for Paediatric Infectious Diseases.
“These data highlight that we should consider the use of this vaccine to protect against MenB [Neisseria meningitiditis serogroup B] disease in toddlers and children,” declared Jason D. Maguire, MD, associate director for vaccines clinical research and development at Pfizer in Pearl River, N.Y.
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The Food and Drug Administration agrees. In April 2018, the agency granted the vaccine, brand name Trumenba, breakthrough therapy status, approving it as the first MenB vaccine for use in 1- to 9-year-olds on the basis of the phase 2 data, Dr. Maguire said. Prior to receiving breakthrough therapy designation, the vaccine was approved in the United States and elsewhere for prevention of MenB disease in 10- to 25-year-olds.
There was a strong impetus for conducting these first-ever clinical trials of a MenB vaccine in children under 10 years of age because roughly one-third of invasive meningococcal disease occurs in children less than 5 years old. The invasive disease, often manifest as meningitis, septicemia, or pneumonia, can be life threatening. Indeed, the overall case-fatality rate of invasive meningococcal disease in the United States is 13.9%. Moreover, survivors often experience lifelong sequelae, including cognitive impairment, hearing loss, and/or limb amputation, he noted.
Dr. Maguire presented both of the phase 2 randomized trials. One included 396 healthy toddlers aged 12-23 months. The other featured 400 healthy children aged 2-9 years, roughly half of whom were age 4 years or younger. In both studies, MenB vaccine was given as a three-dose series at 0, 2, and 6 months, while controls received hepatitis A vaccine at 0 and 6 months and a saline injection at 2 months.
As an overview, both studies showed higher rates of local and systemic reactions than seen in earlier trials conducted in adolescents and young adults; however, these reactions were generally mild to moderate and transient, lasting 1-3 days. And 1 month after the third dose of MenB vaccine, immune responses above the threshold for protection were documented in 72%-100% of cases across the four MenB strains covered by the vaccine. These four strains account for more than 90% of invasive MenB disease isolates found in the United States and Europe.
Dr. Jason D. Maguire
Credit: Bruce Jancin/MDedge News
The toddler trial
Participating toddlers were randomized 2:1 to the vaccine or control group. To minimize the potential risk of the vaccine in such a young and previously unstudied age group, the first 44 MenB recipients received three 60-mcg doses rather than the approved 120 mcg. Based upon the favorable experience with low-dose immunization, the next 220 MenB recipients got the full 120-mcg injections. Both dose levels turned out to be similarly immunogenic.
Fever occurred in 37% of the 120-mcg recipients, compared with 15% of controls who got hepatitis A vaccine and saline. The fever responded to acetaminophen. The rate of severe fever defined as 40° C or more was 0.5% in the MenB vaccine group. No one withdrew from the trial because of fever or any other adverse event.
Other adverse events that occurred more frequently in the MenB vaccine group included irritability, diarrhea, injection site pain, and decreased appetite. The incidence of treatment-related adverse events from dose one through 1 month after dose three was 10.5% in the 120 mcg–dose group and 4.5% in controls. Fifty-one percent of adverse events in the 120-mcg group were categorized as moderate and 13% as severe.
MenB immunization in 2- to 9-year-olds
The 400 participants, average age 4.3 years, were randomized 3:1 to MenB vaccine or the control group. Fever occurred in roughly 25% of MenB vaccine recipients and 12% of controls. No febrile seizures occurred in the study. Thirty-seven percent of adverse events in MenB vaccine recipients were rated moderate, 44% mild.
“Compared to previous studies in adolescents, we did see higher rates of fever, local reactogenicity, and vomiting,” according to Dr. Maguire.
One MenB vaccine recipient withdrew because of an adverse event deemed by investigators to be possibly vaccine related. This was a case of transient hip synovitis in a 2-year-old. Symptoms began a day after the second dose of vaccine and resolved within 13 days with nonsteroidal anti-inflammatory agents alone.
The two randomized controlled trials were sponsored by Pfizer and presented by a company employee.