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An experimental RSV vaccine developed by Pfizer to protect infants — by vaccinating pregnant people — was shown to be effective in preventing severe lower respiratory tract disease, the Food and Drug Administration said Tuesday in an analysis of the data generated to support licensure of the vaccine.

The agency’s analysis said the vaccine was also shown to be effective at preventing non-severe lower respiratory tract RSV disease that required medical attention at 180 days after birth, though at 90 days the vaccine’s efficacy against this endpoint was not statistically significant.


The FDA’s assessment was released in advance of a meeting Thursday of an expert advisory committee, which will study the safety and efficacy data generated in trials of the vaccine and give the FDA guidance on whether it should be licensed.

The vaccine, which goes by the provisional name Abrysvo, would be given to pregnant people between 24 and 36 weeks of pregnancy with the goal of protecting their babies against RSV in the first six months of life by triggering production of maternal antibodies that would pass across the placenta to the fetus. The vaccine, which targets both subtypes of RSV — RSV A and RSV B — is given in a single intramuscular injection.

In a Phase 3 trial conducted in 18 countries, nearly 7,400 pregnant women were randomly assigned to receive either the vaccine or a placebo. The vaccine met one of two primary endpoints, showing a vaccine efficacy against severe RSV of nearly 82% at 90 days, and 69% at 180 days after birth.


A second endpoint, protection against any lower respiratory tract infection caused by RSV in the first 90 days of life, did not reach statistical significance, though at 180 days, there was a statistically significant vaccine efficacy of 51%.

William Gruber, Pfizer’s senior vice president for vaccine clinical research and development, stressed the importance of showing that the vaccine can protect against severe RSV in infants, a group that is hard hit when infected with respiratory syncytial virus.

“One of the things that we wanted to be very clear about is the expectation going into this — like for other respiratory pathogens or pathogens like rotavirus —  that vaccine has its greatest efficacy against more severe disease,” Gruber told STAT in an interview last week. “With on average 58,000 children hospitalized every year in the United States [for RSV] … that has a major impact.”

On the issue of safety, the FDA analysis noted an imbalance between the number of preterm births in the vaccine arm of the trial as compared to the placebo arm. The imbalance was not statistically significant and the number of preterm births in both arms of the trial was below the background rate — the normal rate at which preterm births are seen to occur.

Still, the analysis sent a clear signal that the FDA would like to hear the thoughts of the experts on the advisory committee on this issue.

“The safety data appear generally favorable for vaccine administration, and we noted potential uncertainty based on the numerical imbalance in premature deliveries. FDA will be asking VRBPAC members to vote on whether the results of the vaccine efficacy trial demonstrate evidence of vaccine effectiveness and to vote on whether the safety data support a favorable risk analysis with VRBPAC discussion of the safety data, for example the numerical imbalance observed in premature deliveries,” the analysis said.

The issue looms large over this vaccine because a competing vaccine that was being developed by GSK was dropped when a clinical trial showed a statistically significant imbalance in preterm births among pregnant people who received the vaccine.

Gruber noted that in the Pfizer trial, the imbalance was not seen in all countries, and wasn’t seen in high-income countries. The study had 2.5 times more participants from high-income countries than the other countries; given the higher number, one would expect to see more precision in the data from that segment of the study, he said, but “we’re not seeing this.”

Further, another data point — the rate 0f low-birth-weight babies — actually points away from a safety concern, he said.

“When we looked at low birth weight and particularly low birth weight less than 1,500 grams, then it actually flips,” Gruber said. “There are more low-birth-weight babies in the placebo group than there are in the vaccine group. To my mind, it provides additional reassurance.”

Pfizer has said that if the vaccine is licensed, the company will conduct post-marketing surveillance for preterm births among vaccine recipients. Gruber said he expects it will become clear when the vaccine is administered to larger numbers of pregnant people that the imbalance was “a spurious finding.”

The most common solicited adverse event was fatigue; headache, muscle pain, and injection site pain were also common, though all were graded in the mild and moderate range. Fever after vaccination was uncommon, and was reported by roughly the same percentage of people in the vaccine arm as in the placebo arm.

Seventeen babies born to the participants in the trial died, five born to people in the vaccine arm and 12 to people in the placebo arm. Four of the five deaths in the vaccine arm were ruled unrelated to the vaccine. But with the fifth — an extremely premature infant born at 27 weeks gestation — the FDA said it was “unable to draw definitive conclusions regarding potential relation of this case of extreme prematurity to the investigational product.”

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