An advisory committee convened by the Food and Drug Administration (FDA) has expressed the need for more data regarding the safety of respiratory syncytial virus (RSV) vaccines in infants. This call for caution comes after the FDA partially paused enrollment in clinical trials testing certain RSV vaccines in young children due to safety signals observed in Moderna's pediatric trials.
The advisory committee, which met at the FDA’s request, did not reach a definitive conclusion regarding the cause of the safety signal observed in Moderna’s RSV vaccine trials. However, panel members largely agreed on the necessity of gathering additional information before proceeding further. The committee did not vote on specific safety precautions or whether trials currently on hold could resume.
Safety Signal in Moderna's RSV Vaccine Trials
Investigators in a Moderna trial reported cases of severe RSV in infants between 5 and 8 months old who had received one of two formulations of the company’s vaccine. The study was paused in July, and the FDA subsequently placed a hold on enrolling children under two years of age in all clinical studies testing non-live-attenuated RSV vaccine candidates. This hold also extends to children aged 2 to 5 years who have never been infected with RSV.
According to FDA briefing documents, there are 26 RSV vaccine candidates in pediatric clinical development, with 11 utilizing non-live-attenuated technologies.
Expert Opinions and Concerns
"We are confronted by a very complicated situation," stated Arnold Monto, a panelist and professor emeritus of epidemiology and public health at the University of Michigan’s School of Public Health.
Moderna’s vaccines are mRNA-based. The company markets one formulation of its RSV vaccine for older adults under the brand name mResvia and is testing this and another formulation designed to also protect against human metapneumovirus in children.
Moderna initially tested its RSV vaccines in children between 8 and 24 months old before enrolling infants between 5 and 7 months of age. Among this younger group, five cases of severe RSV were reported in participants who received Moderna’s vaccine, compared to one case in those given a placebo. There was also one case of RSV-associated hospitalization in an older child participant after Moderna proceeded with testing in young infants.
While concerned about the reported cases, advisors noted that the trial's safeguards were effective. Adam Berger, director of clinical and healthcare research policy in the Office of Science Policy at the National Institutes of Health, stated, "What is already in place is working. We just don't really have a good understanding of the mechanism that is driving the safety signal."
Berger also noted that data was only available from Moderna among the 11 pediatric trials on partial hold. "I don't think we can make a generalized answer to a technology based on just having one study. I fully agree there is an absolute safety signal here, and the steps that we're taking are I would support, but I'm not sure I can actually apply that to all mRNA programs," he said.
Additional Considerations
Some advisors noted that many infants enrolled in Moderna’s study were located in Panama, raising questions about potential local factors affecting the immune response. Michael Nelson, professor of medicine and division chief for asthma, allergy, and immunology at University of Virginia Health, highlighted this point.
The committee emphasized the need to better understand immune responses in different age groups and called for continued monitoring of immune responses in trial participants. They expressed interest in further discussions as more data becomes available. None of the advisors called for ending all studies testing RSV vaccine candidates in infants.
Positive Remarks on Existing Preventative Measures
Advisors also spoke positively about Sanofi’s monoclonal antibody Beyfortus, which is approved for temporary RSV protection in infants, and Pfizer’s RSV vaccine used as a maternal immunization to provide passive protection to newborns.
