A committee of vaccine experts voted to recommend the Food and Drug Administration approve Pfizer’s maternal RSV vaccine on Thursday, though the panel expressed some safety concerns.
The Vaccines and Related Biological Products Advisory Committee voted 14-0 that Pfizer’s data showed the vaccine was effective in preventing severe disease in infants born to people who were vaccinated during pregnancy. But on a second question — whether the available data support the safety of immunization with this vaccine — the committee voted 10-4.
Among the committee members who voted that the safety data were insufficient was committee chair Hana El Sahly, a professor of virology and microbiology at Baylor College of Medicine.
While that question was discussed in depth during the meeting, other members of the committee concluded that the benefits of reducing the risk of severe RSV infection in children in the first six months of life carried more weight.
“If the vaccine actually lives up to the data that we’ve seen today, I can guarantee that many infants and their parents will breathe easier in the coming years,” said Jay Portnoy, a professor of pediatrics at Children’s Mercy Hospital in Kansas City.
Pfizer welcomed the VRBPAC decision.
“If approved, our RSV vaccine candidate has the potential to be the first maternal immunization vaccine to help protect infants at first breath through their first six months of life from this potentially serious infection.” said Annaliesa Anderson, Pfizer’s senior vice president and chief scientific officer for vaccine research and development.
This vaccine, which would be marketed under the name Abrysvo, could be a game changer in an arena that has long needed one. Respiratory syncytial virus sends about half a million children to emergency departments in the U.S. every year; somewhere between 58,000 and 80,000 of those children end up being hospitalized.
In a clinical trial, the vaccine was shown to reduce the risk of severe lower respiratory tract disease caused by RSV by 82% at three months after birth and 69% at six months.
The FDA does not have to follow VRBPAC’s advice, but it commonly does. The agency is expected to make a decision before or in August.
If approved, the vaccine will be given between 24 and 36 weeks of pregnancy, not to protect the pregnant person but to generate antibodies that pass through the placenta to the fetus.
This phenomenon, known as passive immunity, means that babies born to vaccinated people have antibodies that should help them avoid developing serious illness when they contract RSV. The virus is so ubiquitous that more than two-thirds of children are infected by the end of their first year; by the end of year two, virtually every child has been infected with RSV.
The pressure RSV places on pediatric health care is enormous and until now there has only been one tool with which to combat it — a monoclonal antibody called palivizumab (sold as Synagis), that requires monthly injections at a cost of about $1,800 per dose (the wholesale acquisition cost). It is reserved for the highest-risk babies.
So there has been great excitement about the possibility of another tool with a price tag that would allow it to be used more broadly. Pfizer hasn’t yet said what it will charge for this vaccine if it is approved but it will be substantially cheaper.
Another potential tool is on the horizon. Sanofi has applied to the FDA for a license for a long-lasting antibody therapy that would be given at birth to protect infants against RSV in the first year of life. It too is expected to be approved this year.
Still, hanging over this meeting was the specter of a decision by rival manufacturer GSK, which last year abandoned a program to develop a maternal RSV vaccine when it saw an increased rate of preterm births in pregnant people who had received the vaccine.
Pfizer also saw more premature births in the vaccine arms of its clinical trials, but the difference was not statistically significant. Furthermore, where GSK’s trial showed an increased risk of infant death — attributed to the increase in premature births — Pfizer reported it did not see that result. Most of the preterm babies in the Pfizer trial were born near full term.
If the vaccine is approved, the company will most assuredly be required to do post-marketing surveillance to see if there is a real association between receiving the vaccine and preterm births.
VRBPAC member Amanda Cohn, director of the division of birth defects and infant disorders at the Centers for Disease Control and Prevention, said on balance, she was comfortable voting in favor of the vaccine. Even babies who are born preterm, she said, will benefit from the antibodies they will get in utero following administration of this vaccine.
But four members of the committee were not convinced that Pfizer had generated enough data to answer the question of the vaccine’s safety.
“I do think that a lot’s at stake if you’re asking one to protect another,” said Paul Offit, a professor of pediatrics and a pediatrician at Children’s Hospital of Philadelphia. Offit voted no on the safety question.
The committee members also expressed concern about the fact that there is evidence — though not generated in clinical trials in pregnant people — that giving this vaccine at the same time as either a flu shot or Tdap, a vaccine the protects against tetanus, diphtheria, pertussis, depresses the immune response to the influenza vaccine and to the pertussis component of Tdap. Pregnant people are urged to be vaccinated against flu and to get a Tdap shot during pregnancy.
El Sahley wondered whether working to lower one risk might raise others.
“From an implementation standpoint, what are we going to tell our OB-GYN colleagues to prioritize and are we confident that giving these vaccines together or in proximity that is closer than one month apart that we would not be negatively impacting the health of the mother and the child?” she asked.
But getting answers to those questions will require monitoring a larger group of vaccinated pregnant people and their infants, colleagues on the committee said.
A large proportion of RSV illnesses are in children in the first weeks and months of life, when their tiny airways make them extremely vulnerable to the damage the virus causes.
RSV deaths in children in the United States are rare — it’s estimated between 100 and 300 kids die here in an average year. But the overall burden of this infection in young children and the pressure it puts on health care is huge.
Two weeks ago, the FDA approved the first-ever RSV vaccine for adults 60 and over.
This story has been updated.