FDA approves RSV monoclonal antibody for infants, young children at high risk

The Food and Drug Administration approved a monoclonal antibody to protect infants and young children from severe illness caused by RSV on Monday, a potential game-changer for a disease that is the No. 1 cause of hospitalization of babies in this country.

Use of the antibody treatment, the brand name for which is Beyfortus, still needs to be recommended by the Advisory Committee on Immunization Practices, an independent expert panel that advises the Centers for Disease Control and Prevention. A special meeting of the ACIP has been set for Aug. 3 to vote on whether to recommend the antibody, and on whether to add it to the Vaccines for Children program, which would require the federal government to pay for it for children without health insurance.

Once the ACIP recommends the product — and it is expected to do so — CDC Director Mandy Cohen will have to sign off on the advice before the antibody could be put into broad use.

“RSV can cause serious disease in infants and some children and results in a large number of emergency department and physician office visits each year,” said John Farley, director of the office of infectious diseases in the FDA’s Center for Drug Evaluation and Research. “Today’s approval addresses the great need for products to help reduce the impact of RSV disease on children, families and the health care system.”

Beyfortus has already been licensed in the European Union, the United Kingdom, and Canada. It was developed by AstraZeneca and will be marketed in the United States by Sanofi.

“Beyfortus represents an opportunity for a paradigm-shift in preventing serious respiratory disease due to RSV across a broad infant population in the U.S.,” Iskra Reic, AstraZeneca’s executive vice president for vaccines and immune therapies, said in a statement.

The antibodies are given in a single injection at or soon after birth to babies born during respiratory syncytial virus season, which typically runs from November to late March. Babies born at other times in the year would be given the injection in their first autumn. Children at high risk of developing severe illness from RSV infection would also be given shots to help protect them during their second RSV season as well.

A Phase 3 clinical trial showed the monoclonal antibody, whose scientific name is nirsevimab, reduced the incidence of RSV-triggered lower respiratory tract infection requiring medical care by 76.4% and cut hospitalizations for RSV infections by 76.8% in healthy full- and near-full-term babies.

Andrew Pavia, chief of the division of pediatric infectious diseases at the University of Utah and director of hospital epidemiology at Primary Children’s Medical Center in Salt Lake City, said being able to dramatically reduce the number of young children who need medical care when they contract this very common infection would be both a boon for families and a pressure valve for the health care system.

“If we’re looking at a 75% reduction in physician visits for kids who get nirsevimab, and a 75% reduction in RSV hospitalizations, that’s a huge impact on parents and on the health care system,” said Pavia, who has consulted for Sanofi on Beyfortus.

“Those beds become available for kids who need cardiac surgery, who have been in car accidents. It really has multiple levels of effect.”

Monday’s approval means Beyfortus beats to the market another product aimed at reducing the risk of severe RSV infections in infants. An RSV vaccine for pregnant people that has been developed by Pfizer generates antibodies that pass to a fetus in the womb, when the vaccine is given late in pregnancy. That vaccine is expected to be approved by the FDA later this summer.

The timing here is tight. A number of respiratory illnesses, RSV among them, have been pushed out of their normal transmission periods in the post-pandemic era. In the past two years, RSV activity has started over the summer and peaked in the fall — several months earlier than usual. It’s not clear if or when RSV seasonality will settle back into its former pattern, so if Beyfortus is to be used to prevent a repeat of last year’s super-charged RSV season, getting the product to the market soon will be crucial.

A spokesperson for Sanofi said the company is positioned to start supplying Beyfortus and does not anticipate any challenges filling demand.

RSV is a major cause of illness among young children, in this country and globally. It is estimated that in any given year in the United States, about 2.1 million children younger than 5 years old receive outpatient care because of RSV; between 58,000 and 80,000 children in that age group are hospitalized because of these infections. While RSV is the second leading cause of deaths among babies worldwide — after malaria — in the U.S. it is estimated that between 100 and 300 children die from RSV infections every year.

The infection is often most severe in very young children, whose lungs are still developing. The young age of these most vulnerable children makes protecting them through more traditional means — vaccination — unworkable. Vaccines given to infants often require multiple doses, administered over a period of weeks or months, to generate adequate protective antibodies. During this time, infants would still be vulnerable to RSV. But Beyfortus contains already formed antibodies that can protect infants against severe disease quickly. Sanofi said studies conducted in adults showed that the antibodies were detectable in the blood of recipients within hours after dosing, reaching peak levels by day 6.

There has long been a need for tools with which to protect children from RSV, and there is relief that this important medical gap is now being filled. But the fact that there are likely to be two different approaches to protecting young children is creating concern about how to maximize the benefits of the products without breaking the bank.

A cost-benefit analysis conducted by the CDC and health economists from the University of Michigan showed there is little additional benefit of giving Beyfortus to a full-term baby whose mother received the Pfizer maternal vaccine, but the price of doubling up produces what one ACIP member called “eye-popping costs.”

Sanofi has not yet said what it will charge for Beyfortus in the U.S., but the CDC-University of Michigan analysis used the figure of $500 a dose, based on a cost analysis the companies had submitted.

“Our goal remains to work closely with payers and authorities to determine an appropriate price point based on cost effectiveness and implementation in all infants,” a Sanofi spokesperson said. “We expect Beyfortus to be priced similarly to an innovative pediatric vaccine series, in accordance with the value and innovation it delivers.”

The spokesperson said Sanofi would reveal more about the price of Beyfortus “closer to the RSV season.”

AstraZeneca also declined to say what it is charging for the product in the U.K., Europe, or Canada. “Though we cannot speculate price at this time, we’re dedicated to bringing this protective option to the broad infant population,” a spokesperson said.

The Beyfortus approach has some advantages over the maternal vaccine approach Pfizer is developing. Studies suggest the monoclonal antibodies stick around for longer — perhaps as much as twice as long — than those that pass to fetuses via the placenta when a pregnant person is vaccinated.

Administration of the antibody shots can be timed to RSV season, so babies born when the virus isn’t circulating would only get the shot in the autumn, to give them protection over the winter. That flexibility is missing from the maternal vaccination approach; babies born to pregnant people in the early spring, for example, may have few antibodies left when the virus is starting to circulate. And if the pregnant person is vaccinated too late in pregnancy — or the baby is premature — the pregnant person’s immune system may not have had enough time to develop a robust response.

But the cost of the monoclonal antibodies will be higher than that of the vaccine — perhaps substantially so. That has raised concerns about whether the product will be covered by the Vaccines for Children program. If it was not added to the VFC program, children from low-income households are unlikely to be able to get these shots.

The fact that the ACIP meeting will include a vote on whether the product should be added to the Vaccines for Children program suggested the behind-the-scenes discussions of what this addition might do to the budget of the program have been settled. The ACIP members have spoken often about how unacceptable inequitable access would be; they are likely to strongly support adding Beyfortus to VFC.

Both the monoclonal antibodies and the maternal vaccine may also run into acceptance issues. Some people are reluctant to be vaccinated during pregnancy, and even those who agree to some vaccines may be hesitant to add another shot to a growing list of jabs — influenza, Covid, the combined tetanus, diphtheria, and pertussis vaccine — that they are urged to get while pregnant.

A small survey the CDC conducted among pregnant people found that 28% indicated they would prefer to be vaccinated against RSV rather than have their baby receive the monoclonal antibody shot; 25% indicated they would prefer to forgo vaccination and let their baby get Beyfortus. A further 38% indicated they wanted a belt-and-suspenders approach — a vaccine for themselves while they are pregnant and the antibody shot for their baby after birth — which global health experts warn would be an unfortunate waste of resources.