Wednesday, 29 May, 2024
HomeRegulatoryFDA panel green-lights RSV pregnancy jab, but concerns persist

FDA panel green-lights RSV pregnancy jab, but concerns persist

Despite some concerns, a US Food and Drug Administration (FDA) advisory panel has approved a Pfizer vaccine to be given to pregnant women that prevents respiratory syncytial virus (RSV), a potentially deadly threat to infants worldwide which kills several hundred under-fives each year.

The vaccine would be the first to protect babies from the virus, reports The New York Times.

Fourteen agency advisers unanimously agreed that the vaccine was effective – the FDA typically follows the recommendations of its advisory panels.

While 10 of them agreed the jab was safe, some expressed concern about elevated rates – not all statistically significant – of preterm births among mothers who got the vaccine compared to those who received a placebo.

The vote follows the FDA’s earlier decision to approve the first RSV vaccine for older adults in the US. Several other options are still being evaluated.

The Pfizer vaccine for pregnant women, called Abrysvo, is being reviewed ahead of another option submitted to the FDA that would be given to infants, a monoclonal antibody shot meant to provide five months of protection.

RSV is most severe in young infants and older adults, with up to 80 000 children under fives hospitalised with it each year. and up to 300 dying. (As many as 160 000 adults aged 65 and older are admitted to hospital every year with the virus, and about 10 000 die.)

The youngest infants face the greatest risk, with those under six months twice as likely to be hospitalised compared with older babies or children. Efforts to test a vaccine in babies began in the 1960s but were abandoned when the shot caused more severe cases.

The vaccine under review was tested in about 7 300 women after the 24th week of pregnancy. About half received a placebo, and half were given the vaccine as a shot. For the first 90 days after birth, six infants in the vaccination group had a serious case of RSV, compared with 33 in the placebo group, translating to an efficacy of nearly 82%.

The study, published in The New England Journal of Medicine, showed that for six months after birth, the vaccine was 69% effective. In the treatment group, 19 babies fell seriously ill compared with 62 in the placebo group.

The main safety concern during the hearing was whether the vaccine was linked to preterm birth, a safety signal that led GSK to halt its trial of a similar RSV vaccine that was being tested in pregnant patients, said Dr Hal Barron, a former company executive.

The FDA approved that vaccine, called Arexvy, for older adults earlier this month. (Like GSK, Pfizer tested the same vaccine formula in older adults and infants.)

“We quickly halted the trial based on it confirming that the signal was real,” Barron said in a March 2022 presentation to investors, “but we are still puzzled as to exactly why this occurred.”

The label for the GSK vaccine says that in tests of pregnant women, 6.8% receiving the treatment had preterm births, compared to 5% in the placebo group.

In the Pfizer study, premature delivery was reported in 5.6% of the pregnancies in the treatment group, compared with 4.7% in the placebo group. FDA officials reported that the difference was not statistically significant.

Pfizer said if the drug were approved, it would conduct a post-approval study of real-world use of the vaccine, monitoring health records for the incidence of preterm birth and other possible problems.

Agency advisers, though, expressed scepticism about a plan to use data generated from healthcare billing records to monitor vaccine safety, saying that could make it hard to link a parent who got the vaccine to the child.

Dr Hana El Sahly, advisory committee chairwoman and professor of virology at Baylor College of Medicine, said the number of preterm births among those given the vaccine in a prior Pfizer study, in the main study under review, and in the GSK study of a similar product, was concerning, particularly given the US is not in the midst of an RSV outbreak. She said the pattern should have been examined more carefully.

“That was a big missed opportunity and I feel it’s unfair that we kicked the can down the road to the larger public,” said El Sahly, who voted “no” to the question about whether the safety data were adequate.

Another remedy under regulatory consideration is a monoclonal antibody shot developed by Sanofi and AstraZeneca, called nirsevimab. It is meant to be given at the hospital to babies born during the winter or autumn, said Jonathan Heinrichs, a Sanofi executive.

The medication is under FDA review and was found, in one study of nearly 2 500 infants, to reduce cases of severe RSV by 75%.

Study details

Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants

Beate Kampmann, Shabir Madhi, Iona Munjal, Eric Simões, Barbara Pahud, Conrado Llapur, Jeffrey Baker, Gonzalo Pérez Marc, David Radley, Emma Shittu, Julia Glanternik, Hasra Snaggs, et al., for the MATISSE Study Group*


Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)–associated lower respiratory tract illness in newborns and infants is uncertain.

In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks’ gestation to receive a single intramuscular injection of 120 μg of a bivalent RSV prefusion F protein–based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points.

At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively).

RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified.


NEJM article – Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants (Open access)


The New York Times article – F.D.A. Panel Recommends R.S.V. Vaccine to Protect Young Infants (Restricted access)


See more from MedicalBrief archives:


Pfizer to apply for approval of first maternal RSV vaccine


UK approves one-shot RSV vaccine for babies


Significant drop in newborns’ RSV risk with vaccine for pregnant women






MedicalBrief — our free weekly e-newsletter

We'd appreciate as much information as possible, however only an email address is required.