FDA advisors support RSV vaccine for pregnant women

WASHINGTON — A first-of-its-kind RSV vaccine for pregnant women protects their newborns from the dreaded respiratory virus — and federal health advisers on Thursday backed Pfizer’s shot despite some lingering questions.

RSV fills hospitals wheezing in children every fall and winter, and the virus hit earlier than usual, and especially hard in the US last year.

If the vaccine succeeds, “many babies and their parents will be able to breathe easier for years to come,” said Dr. Jay Portnoy, a member of the Food and Drug Administration’s advisory panel at Children’s Mercy Hospital in Kansas City, Missouri.

The idea: Give women a single injection late in pregnancy, between 24 and 36 weeks, so they develop antibodies against RSV that cross the placenta — just as they pass on protection against other bugs to their babies.

At Pfizer international of nearly 7,400 pregnant women, maternal vaccination proved 82% effective in preventing severe RSV during the first three months of life in the most vulnerable infants. At 6 months of age, it still showed 69% protection against severe disease.

Pfizer said there were no signs of safety issues, but the FDA asked its scientific advisers to consider whether a small difference in preterm births between vaccinated moms and those who received a sham shot was a concern. Debate over whether this was really a hint of trouble or just a fluke dominated the panel’s daylong meeting.

Pfizer has promised to closely monitor real-world use of the vaccine for more evidence. In the end, advisers unanimously decided the shot was effective — and voted 10-4 that there was sufficient safety data. The FDA will consider Thursday’s recommendations in making a final approval decision.

“If you’re in any way risking preterm birth with this vaccine, I think you’re going to have to pay a big price,” said Dr. Paul Offit of the Children’s Hospital of Philadelphia, one of the panelists who voted no on the safety issue.

If the FDA ultimately approves the maternal vaccine, it will mark the second milestone in the decades-long quest to prevent respiratory syncytial virus. Earlier this month, the FDA approved the world’s first RSV vaccine, GSK’s competing vaccine for the elderly, who are also at high risk. There is no vaccine for children yet, but Pfizer is about to start testing it.

Here’s what you need to know:

For most healthy people, RSV is a nuisance similar to the common cold. But it can be life-threatening for the little ones – an infection deep in the lungs can cause pneumonia or prevent babies from breathing by inflaming their tiny airways. According to the Centers for Disease Control and Prevention, 58,000 to 80,000 children under the age of 5 are hospitalized and 100 to 300 die each year in the United States alone.

“All young infants are at risk of severe disease from RSV,” but delaying exposure for even a few months reduces that risk, said Dr. Kathryn Fleming-Dutra of the CDC.

The Pfizer vaccine is not designed to prevent RSV infection, but to avoid worse outcomes. In late-stage testing, six infants born to vaccinated mothers had severe RSV disease in the first three months of life, compared with 33 infants whose mothers received sham vaccinations. In addition, the vaccine halves the likelihood of needing medical care for RSV infection in infants under 6 months of age.

The company predicts that the US could prevent up to 20,000 infant hospitalizations and 320,000 doctor visits per year if enough pregnant women were vaccinated.

Reactions to the vaccine usually included mild pain at the injection site and fatigue. As for prematurity, vaccinated mothers had slightly more premature babies – 5.7% versus 4.7%. The vast majority were born just a few weeks early. That’s better than the national preterm birth rate — 1 in 10 babies in the U.S. overall was born premature last year — and the study’s imbalance was not statistically significant, meaning it could have been due to chance.

Rival GSK has halted its own maternal RSV vaccine trials due to prematurity concerns, raising questions about Pfizer’s vaccine. Pfizer said the premature difference in its study was caused by participants in South Africa – for unknown reasons – and no difference was seen in the US or other high-income countries.

“Are you holding the potential benefits of a vaccine hostage” without clear evidence of a problem, Dr. William Gruber, a senior vice president at Pfizer, asked the panelists.

“There is confidence that the vaccine works and will keep babies out of the hospital in the United States this winter,” he said.

A total of 17 babies died during the study, five born to vaccinated mothers and 12 to those who received a sham injection. The researchers did not think any of the deaths were related to the vaccine, but the FDA said it “cannot rule out the possibility” that one infant’s death, which resulted from extreme prematurity, could be related.

The safety of vaccines is always scrutinized, but regulators are especially mindful of a major setback in the 1960s, when an experimental RSV shot made the infection worse in children. Scientists eventually figured out the problem, and the RSV vaccines being developed today are made using safer, more modern methods, but they were still first tested on older people.

FDA advisers also cautioned that it’s unclear what other vaccines can be given to pregnant women during the same doctor’s visit. They pointed to data suggesting that the whooping cough vaccine does not appear to be as effective when pregnant women receive it at the same time as the RSV shot.

FDA advisers have already recommended approval of Pfizer’s vaccine for the elderly, and the agency is expected to make a decision by the end of the month. Whether to use the same vaccine in pregnant women, the FDA will make a separate decision, expected in August.

Meanwhile, rival GSK is gearing up for autumn immunizations with its RSV vaccine for the elderly. First, CDC advisers will discuss next month whether all seniors should be vaccinated or only those at high risk.

Vaccines are not the only progress expected. High-risk infants can receive monthly doses of the protective drug during RSV season, although CDC data show that too few are receiving it. European regulators recently approved the first single-dose option from Sanofi and AstraZeneca, opening up this type of protection to more babies. FDA advisers will also discuss the drug next month.