aAn experimental RSV vaccine developed by Pfizer to protect babies — by vaccinating pregnant people — was found to be effective in preventing serious lower respiratory illnesses, the Food and Drug Administration said Tuesday in an analysis of the data it released. have been generated to support the vaccine’s licensing status.
The agency’s analysis said the vaccine was also shown to be effective in preventing non-severe RSV lower respiratory tract disease that required medical care 180 days after birth, although the vaccine’s efficacy against this endpoint was limited after 90 days was not statistically significant.
The FDA’s review was released ahead of a Thursday meeting of an expert advisory committee, which will review the safety and efficacy data generated in trials of the vaccine and provide FDA guidance on whether it should be licensed.
The vaccine, tentatively named Abrysvo, would be given to pregnant people between 24 and 36 weeks gestation with the aim of protecting their babies against RSV in the first six months of life by triggering the production of maternal antibodies that would be passed through the placenta to the fetus. The vaccine, which targets both subtypes of RSV – RSV A and RSV B – is administered in a single intramuscular injection.
In a phase 3 trial conducted in 18 countries, nearly 7,400 pregnant women were randomly assigned to receive the vaccine or a placebo. The vaccine met one of the two primary endpoints, showing vaccine efficacy against severe RSV of nearly 82% at 90 days and 69% at 180 days postpartum.
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, although there was a statistically significant vaccine effectiveness of 51% after 180 days.
William Gruber, Pfizer’s senior vice president of vaccine clinical research and development, stressed the importance of demonstrating that the vaccine can protect against severe RSV in infants, a group that is severely affected when they become infected with respiratory syncytial virus.
“One of the things we wanted to be very clear about is the expectation that goes into this – as it is for other respiratory pathogens or pathogens like rotavirus – that vaccine has the greatest efficacy against more serious diseases,” Gruber told in an interview last week STAT. . “With an average of 58,000 children hospitalized each year in the United States [for RSV] … that has a major impact.”
In terms of safety, the FDA analysis found an imbalance in the number of preterm births in the vaccine arm of the study compared to the placebo arm. The imbalance was not statistically significant and preterm birth rates in both arms of the study were below the background rate – the normal rate at which preterm births occur.
Still, the analysis sent a clear signal that the FDA would like to hear the opinion of the experts on the advisory committee on this.
“The safety data generally appear favorable for vaccine administration and we noted potential uncertainty based on the numerical imbalance in preterm delivery. The FDA will ask VRBPAC members to vote on whether the results of the vaccine effectiveness study demonstrate evidence of vaccine effectiveness and vote on whether the safety data supports a favorable risk analysis with VRBPAC discussion of the safety data, for example, the numerical imbalance observed in premature deliveries,” the analysis said.
The problem arises with this vaccine because it is a competing vaccine developed by GSK was dropped when a clinical trial showed a statistically significant imbalance in preterm birth in pregnant people who received the vaccine.
Gruber noted that in the Pfizer process, the imbalance was not seen in all countries, including 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 more precision in the data from that portion of the study, he said, but “we’re not seeing this.”
Further, another data point — the number of low birth weight babies — actually points away from a safety concern, he said.
“When we looked at low birth weight and very low birth weight of less than 1,500 grams, that’s when it really flipped,” Gruber said. “There are more low birth weight babies in the placebo group than in the vaccine group. That gives me extra security.”
Pfizer has said that if the vaccine is licensed, the company will conduct post-marketing surveillance for preterm birth 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 false finding”.
The most common unwanted side effect was fatigue; headache, myalgia and pain at the injection site were also common, although all were classified in the mild and moderate range. Post-vaccination fever was infrequent and reported by about the same percentage of people in the vaccine arm as in the placebo arm.
Seventeen babies from the trial participants died, five from people in the vaccine arm and 12 from people in the placebo arm. Four out of five deaths in the vaccine arm were unrelated to the vaccine. But with the fifth — an extremely preterm baby born at 27 weeks gestation — the FDA said it was “unable to draw definitive conclusions about the possible relationship of this case of extreme preterm birth to the investigational product.”