A: Pfizer’s clinical trial of a new RSV vaccine in pregnancy showed high vaccine efficacy against severe disease in infants. The FDA advisory committee discussed an observed difference in premature births in the placebo vs. vaccine group, but concluded that the difference was likely due to chance rather than from the vaccine itself.
TL;DR: The new RSV vaccine is highly effective and has the potential to save millions of infants worldwide from severe illness and death. The safety of the vaccine from the trial looks good, but scientists will carefully monitor the data for any safety signals including prematurity as more people get the vaccine.
RSV (respiratory syncytial virus), often a mild respiratory illness, is the leading cause of hospitalization in infants. We heard a lot about RSV and the “tripledemic” this past winter when pediatric hospitals were overwhelmed with the return of RSV, the flu, and COVID-19 at the same time. The FDA recently approved the use of two RSV vaccines in people 60 and older and will soon decide whether to approve a vaccine for pregnant people that protects infants after birth.
Before the FDA can approve a vaccine or drug, an advisory committee meets to discuss the data and make a recommendation to the FDA. The VRBPAC (Vaccines and Related Biological Products Advisory Committee) met on May 18th and agreed that the vaccine has high efficacy, meaning that RSV infections were significantly lower in infants whose mothers had been vaccinated compared to placebo. It’s also the panel’s job to discuss safety data. The panel discussed at length clinical trial data that showed slightly more babies were born early in the vaccine group than the placebo group. A statistical analysis showed that this difference did not occur in all countries and was small enough to likely be due to chance. The difference between the two groups (placebo and vaccine) was even smaller when data was analyzed looking only at early-preterm births (<34 weeks of gestation, who are at increased health risk compared to >34 weeks gestation). Overall prematurity in both groups was much *lower* than what we typically see in the general population, likely reflecting the fact that trial volunteers are often healthier than the general population.
Because of the seriousness of a possible increased risk of prematurity, the panel discussed these data at length. One of the four members who voted against approving the vaccine, Dr. Paul Offit, expressed high confidence in the efficacy and safety data presented by Pfizer, but said he did not feel comfortable with an approval in light of concerns for increased preterm birth in another RSV vaccine, manufactured by GlaxoSmithKline. A few of the other dissenting members cited this other vaccine trial in their rationale for withholding approval.
A few committee members wanted additional data, but the other 6 advisors recommended vaccine approval based on the existing trial data and the potential benefit to infants worldwide. They pointed out that careful post-approval observational studies would provide the best insight into any potential adverse effects, and that active data analysis allows these effects to be detected quickly (within days to weeks). The FDA typically follows the advice of the VRBAC in making their final approval decision.
The committee also pointed to important global benefits of the new vaccine. A vaccine approved in the US can potentially be used in low or middle income countries, where most severe RSV illness occurs but hospital access is limited.
Even if the vaccine is approved by the FDA, careful monitoring will continue. Prematurity is one of 4 adverse events of interest actively monitored by the FDA.
The slightly higher number of premature births in the vaccine group compared to placebo group for the new RSV vaccine was not “statistically significant”– meaning it is most likely due to chance. In contrast, the trial provided strong evidence that the vaccine reduces the risk of severe infections, hospitalizations and deaths in both premature and term infants. RSV sends close to half a million children to emergency departments in the U.S. every year, so this is really huge news!
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