A recently approved treatment was supposed to protect babies from RSV, but demand is outpacing the supply of the medication.
The U.S. Food and Drug Administration approved nirsevimab, an antibody that sticks to and prevents Respiratory Syncytial Virus from infecting cells, in July. The Centers for Disease Control and Prevention (CDC) then recommended the medication for all babies either born during the RSV season or those up to eight months old entering their first RSV season, which runs from about November to March. RSV can be a dangerous and potentially deadly disease, especially for infants; about 58,000 to 80,000 children under five are hospitalized each year and up to 300 die from RSV in the U.S., according to the CDC.
The antibody is not a treatment for RSV, since it works to prevent infection, not treat it, but it’s also not a vaccine, although it works similarly and provides short term protection for infants. The antibodies in the shot essentially fill in for the antibodies that babies can’t make yet in enough quantities to fend off the virus. Because it’s not a vaccine, it’s important that babies get the antibodies at the right time, during RSV season, to give them the best chance of avoiding infection.
Why isn’t there enough nirsevimab?
However, on Oct. 23, the CDC alerted health care providers that the drug was in short supply, and recommended that available doses be reserved for babies at the highest risk of complications from RSV—including those six months old or younger, as well as those with heart and lung conditions. Responding to the alert, pediatricians informed parents that if their babies didn’t meet these higher-risk criteria, they wouldn’t be able to receive the drug.
Sanofi, which distributes nirsevimab (which is sold under the brand-name Beyfortus), in partnership with AstraZeneca, which manufactures the drug, both cited unexpected high demand for the shortage. “Despite an aggressive supply plan built to outperform past pediatric immunization launches, demand for this product…has been higher than expected,” says a Sanofi spokesperson. To address the shortage, an AstraZeneca spokesperson says “we are maximizing the efficiency of our production capabilities and have recently increased our production and packaging capacity through the addition of other manufacturing sites.”
Dr. Robert Frenck, professor of pediatrics and director of vaccine research at Cincinnati Children’s Hospital, says that a couple of factors likely contributed to the inadequate supply, including pent-up demand that hit all at once, and difficult financial decisions doctors had to make about how many doses to purchase. Because the antibody is recommended for babies up to eight months old in their first RSV season, any baby born as far back as March is eligible for nirsevimab now. With some 3.5 million babies born in the U.S. each year, that’s about 2.4 million babies possibly showing up at doctors’ offices and hospitals to get the drug.
Moving forward, the good news is that the mismatch will likely be resolved by next year. While there will always be a surge in demand for the medication just before the RSV season, next year it’s likely that babies born in the fall will receive nirsevimab before they leave the hospital, thus alleviating some of the demand as the RSV season starts. “This year we have millions of babies all of a sudden who need it, and we didn’t have the opportunity to spread it out based on when they were born,” says Frenck.
There’s another artifact of introducing any new drug that probably also contributed to shortfalls in some doctors’ offices, which has to do with how doctors order medications. Pediatricians in private practice pay for the drugs up front, counting on getting reimbursed by insurers. The CDC included nirvsevimab in the Vaccines for Children program, meaning that the government would cover the cost of the drug for babies who are under- or uninsured, which accounts for about half of babies born in the country each year. The other half is covered by private payers, and while these insurers are required to reimburse for drugs included in the Vaccines for Children program, the amount of coverage, and the timeliness of setting up administrative procedures for getting reimbursed are not uniform from company to company. Given the approximate cost of $450 a dose, that left some doctors with hard decisions about how much nirsevimab to order, and those who delayed can no longer place orders because of the short supply. “Private health insurers are not a single animal,” says Dr. Jesse Hackell, chair of the committee on practice and ambulatory medicine at the American Academy of Pediatrics (AAP). “Having a requirement to cover doesn’t mean that the reimbursement is loaded into [each insurance company’s] system. [As a pediatrician] you don’t want to submit a claim to an insurer without knowing first that it won’t simply be rejected as an unrecognized code.”
Who is getting the nirsevimab that’s currently available?
The CDC and the AAP recommend that doses that are available should first go to the youngest babies, under six months, since they are at higher risk of developing complications from RSV. The drug should also be prioritized for babies with congenital heart problems or lung conditions that would make them more vulnerable to the virus.
Are there any other options to protect babies from RSV?
There is another drug that prevents RSV infections, palivzumab (sold under the brand name Synagis). Like nirsevimab, it’s an antibody that can reduce infections with the virus—but unlike nirsevimab, which is just a single shot, palivzumab requires monthly injections throughout the RSV season. The drug is also only approved for a specific group of high-risk babies, including those who are born prematurely and have heart or lung conditions.
Given the shortage of nirsevimab, most doctors are continuing to use palivizumab for babies who qualify for the drug, rather than switching them to nirsevimab. That way, available doses can be reserved for high-risk babies who don’t meet the strict criteria for palivizumab.
Doctors can prescribe drugs off label, or for uses other than those that have been regulator-approved, but pediatricians are reluctant to consider expanding use of palivizumab to otherwise healthy babies for a number of reasons. “The exciting thing about nirsevimab is that it behaves very differently than palivizumab,” says Frenck, so they medications aren’t necessarily interchangeable. He notes that studies of palivizumab only included higher risk infants, and it’s not clear how healthy babies will respond to the drug. In addition, even the studies of higher-risk babies “never really had data showing significant decreases in hospitalizations or ICU admissions,” he says. “The effectiveness was not as high as we had hoped.”
There is also a lower dose of nirsevimab—which is half the approved dose currently in shortage, and which Sanofi and AstraZeneca say is available and in good supply. But the CDC and AAP warned doctors against simply doubling the dose to meet demand. The 50mg dose is intended for smaller babies under 11 pounds, mostly newborns, who are more vulnerable to RSV complications, and pediatricians say that doubling a dose to protect an older infant means two younger babies might not receive the drug. Plus, “two times 50mg of a drug doesn’t mean that it’s the same as 100mg of that drug,” says Dr. Richard Malley, professor pediatrics at Harvard Medical School and at Boston Children’s Hospital.
“Doubling the dose hasn’t really been studied so we can’t speak to the efficacy and safety of combining two doses,” adds Dr. Lori Handy, associate director of the vaccine education center at the Children’s Hospital of Philadelphia. Aside from the medical questions, there are also financial barriers to using either palivizumab or the lower nirsevimab dose off label. Insurers aren’t likely to cover such use, which means parents would have to pay for such use, if doctors agree to it, out-of-pocket.
Moms—and grandparents—can play a role
Another way to address the shortage is to lessen the demand, by ensuring that pregnant people close to delivering get immunized with the RSV vaccine that the FDA also approved this year to protect newborns. Moms who are vaccinated from their 32nd through 36th weeks of pregnancy can pass along antibodies they make against RSV to their babies, protecting them from the day they are born. “The vaccine for pregnant people has about the same efficacy in protecting babies in the first six months of life as nirsevimab,” says Frenck.
There are also two vaccines, made by GSK and Pfizer, for people 60 years and older, another population that is more likely to be hospitalized with RSV. So ensuring they are vaccinated could be another way to protect babies from getting exposed to the virus.
What’s the best way to protect babies who can’t get nirsevimab?
Pediatricians are reassuring parents that despite the fact that this season was supposed to be the first in which they could offer them something to protect their babies from RSV, most healthy babies who get infected won’t get sick enough to be hospitalized. In fact, most infants have battled and successfully recovered from RSV by the time they are two years old—nirsevimab is mostly a safety net to hopefully reduce the chances that more vulnerable babies end up in the hospital. Even with the drug, doctors say families should focus on the basic ways to prevent spread of any virus, which applies to influenza and COVID-19 as well as RSV: wash your hands frequently, especially before coming in contact with infants; keep sick toddlers (or those who may have come in contact with other sick kids) away from infants; and avoid crowded gatherings. And making sure everyone who comes in contact with infants is up to date on their flu and COVID-19 vaccines could also help babies avoid exposure to not just RSV, but other respiratory diseases as well.