Moderna has paused its mRNA RSV (Respiratory Syncytial Virus) vaccine trial for children after five infants were hospitalized with severe respiratory complications.
The pause follows the FDA’s recent decision to halt enrollment in similar trials, citing safety concerns for children under two years old. The announcement was made during Thursday’s FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting, where panelists discussed the safety implications of Moderna’s findings, according to Fierce Pharma.
“This all seems like an incredible conundrum with lots of unanswered questions remaining—lots to still learn,” said Henry Bernstein, a professor of pediatrics at Hofstra/Northwell.
The trial in question, mRNA-1365-P101, was designed to evaluate the safety, tolerability, and immunogenicity of two mRNA-based vaccines, mRNA-1345 and mRNA-1365, intended to protect infants and toddlers against RSV.
According to the FDA briefing document, “FDA was notified of a study pause in Phase 1 study mRNA-1365-P101 due to a study pause criterion being met. A potential safety signal for RSV sLRTI was identified, and as additional information accrued, an imbalance in cases of RSV sLRTI was noted, with more cases identified in the vaccine groups compared with the control group. This raised a concern for possible VAERD.”
During the trial’s younger cohort phase (ages 5 to <8 months), severe RSV-associated lower respiratory tract infections (LRTIs) were more common in vaccinated participants than in those who received a placebo. Trial data revealed:
Five cases of severe RSV-LRTI occurred in vaccinated infants who received lower doses of the vaccine.
Only one case was reported in the placebo group.
Symptomatic RSV infections progressed to severe illness in 26.3% of vaccinated infants, compared to 8.3% in the placebo group.
The trial was paused based on a pre-specified safety criterion, which required halting if severe RSV-LRTI with RSV-positive PCR was observed in at least two participants. After meeting this threshold, Moderna ceased enrollment and dosing across all study cohorts and notified regulators, including the FDA.
The FDA placed the trial on clinical hold, citing an “unreasonable and significant risk of illness or injury.” This decision affects ongoing studies involving infants aged 5 months to <24 months across multiple international sites.
While Moderna and the FDA emphasize a cautious approach, some critics argue the issue lies in the broader “vaccine-first” strategy. Dr. Arnold Monto of the University of Michigan noted the need for rigorous evaluation of RSV vaccines “on a platform-by-platform basis,” underscoring that the unique risks associated with mRNA vaccines remain poorly understood.
