麻豆传媒

The tide may be turning on respiratory syncytial virus (RSV), a seasonal scourge that's responsible for a substantial number of hospitalizations and deaths among older people and young children each year.

In the span of just a few months, the FDA has approved two vaccines and a monoclonal antibody for use in specific populations with the aim of bringing that burden down.

The two vaccines -- one from Pfizer (Abrysvo) and one from GSK (Arexvy) -- can be used in older adults, and Pfizer's vaccine is also approved for pregnant people, aimed at protecting their babies against the virus.

In addition, Sanofi's monoclonal antibody nirsevimab (Beyfortus) can be given to the youngest children as a single intramuscular injection ahead of their first RSV season, as well as at-risk children ahead of their second RSV season.

The pediatric product has been particularly celebrated by pediatricians and public health experts. During the CDC's Advisory Committee on Immunization Practices (ACIP) meeting for nirsevimab, Sarah Long, MD, chair of ACIP's Maternal Pediatric RSV Work Group, called it a "milestone."

"[Parents] should be very, very much relieved that they won't have to be concerned about the likelihood that their child could be hospitalized with RSV disease," Long said at the meeting.

ACIP also has weighed in on use of the vaccines for older adults, but it has yet to weigh in on the maternal vaccine recently approved by the FDA.

Nonetheless, infectious disease experts are still discussing the new landscape of RSV prevention and how best to use these new tools to make this RSV season and future ones easier on Americans.

Vaccines for Older Adults

Both GSK's Arexvy and Pfizer's Abrysvo are approved for adults ages 60 and up. In May, Arexvy became the first RSV vaccine ever approved in the U.S.

William Schaffner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, and a spokesperson for the Infectious Diseases Society of America (IDSA), said older Americans can get the RSV shot now.

"We can start giving this right now because it's supposed to, according to the data, provide substantial long-term protection through at least one RSV season, and maybe longer," Schaffner told 麻豆传媒. "It looks as though there is indeed longer-term protection than we get with flu or COVID [vaccines]."

Both vaccines target the RSV prefusion F protein, but Abrysvo is bivalent, targeting both RSV A and RSV B strains, while Arexvy is adjuvanted with a proprietary adjuvant made by the company.

The effectiveness of Pfizer's Abrysvo is supported by data from the RENOIR trial, which was and involved more than 34,000 people ages 60 and older. An interim analysis found the vaccine efficacy was 66.7% against two or more lower respiratory tract RSV symptoms, and 85.7% against three or more symptoms.

The effectiveness of GSK's Arexvy is supported by data from the AReSVi-006 trial, which was also published in the . It involved almost 25,000 adults 60 and over, and an interim analysis revealed an efficacy of 82.6% against RSV-associated lower respiratory tract illness, and 94.1% against severe RSV illness.

Guillain-Barré syndrome occurred in both trials, and the FDA and trial investigators said it was likely to be related to vaccination. For Abrysvo, there were two cases seen at 7 and 8 days following vaccination, and for Arexvy, one case occurred 9 days after vaccination.

In addition, for Arexvy, atrial fibrillation within 30 days was reported in 10 vaccine recipients versus four placebo patients.

"Of course you're giving [the vaccine] to a very high-risk population," Schaffner said. "Older persons are the ones who get [atrial fibrillation], but that will be looked at very carefully going forward."

CDC's shared clinical decision making for adults 60 and older, noting that those in this age group at highest risk for severe disease include those with chronic conditions such as lung diseases, heart failure and coronary artery disease, immunocompromise, and other conditions.

"Not every 60-year-old needs to get this vaccine," said Aaron Glatt, MD, of Mount Sinai South Nassau, who is also a spokesperson for IDSA. "I would definitely give it to a 62-year-old with lung disease. I wouldn't give it to a 72-year-old who's perfectly healthy otherwise. But if they want to get it, no problem."

It's not yet clear how the vaccine will hold up for a second RSV season in older adults. Data on Arexvy showed that efficacy against lower respiratory tract disease fell to 77% in the middle of season two, with protection against severe disease falling to 85%. For Abrysvo, protection against infection with three or more symptoms fell to 79% by the middle of the second season, with protection against infection with two or more symptoms falling to 49%.

While there's evidence that it's fine to give the flu shot and COVID shot at the same time, there's less data and experience with adding the RSV vaccine to that combination. Schaffner recommended giving the RSV shot 2 weeks on either side of COVID and flu shots.

Monoclonal Antibody for Kids

Pediatricians are excited about the promise of nirsevimab, which stands to reduce the burden of hospitalization for young children.

ACIP has recommended that all infants younger than 8 months born during or approaching their first RSV season get one intramuscular shot of the monoclonal antibody.

Children ages 8 to 19 months who are at increased risk of severe disease and approaching their second RSV season can also get one shot of the drug, ACIP said. The agency defined these at-risk kids as those who are immune compromised; those with chronic lung disease who require some medical support; and those with cystic fibrosis.

The agency also included Alaska Native and Native American children in this high-risk group given the increased risk of hospitalization for these kids.

Data supporting the treatment for infants in their first RSV season come from a and the . The phase IIb trial showed a 70.1% lower incidence of medically attended RSV-associated lower respiratory tract infection with nirsevimab. In the MELODY trial, a single dose of the drug reduced the risk of medically attended lower respiratory tract RSV infection by 74.5% in the 150 days after administration compared with placebo.

The supported use of nirsevimab during a second RSV season in vulnerable children up to age 2.

Sean O'Leary, MD, of the University of Colorado and chair of the American Academy of Pediatrics (AAP)'s committee on infectious diseases, said the hospitalization data from the phase IIb study -- a 78.4% lower incidence of hospitalization with nirsevimab versus placebo -- were "impressive."

"This is the leading cause of hospitalization in infants in the U.S., so if you can knock out four of five hospitalizations, that's incredible," O'Leary told 麻豆传媒. "These hospitalizations can be a real burden on families. Many children end up in the ICU."

"There are between 100 and 500 deaths per year from RSV in children in the U.S., and these are going to be almost entirely preventable with this new product," he added.

Another monoclonal antibody, palivizumab (Synagis), is approved to prevent serious lower respiratory tract disease due to RSV, but in high-risk children only. It's also given monthly, instead of a one-time dose like nirsevimab.

O'Leary said it's generally fine for children to get nirsevimab at the same time as their COVID and flu shots, though only a small group of kids will fall into this category since the vaccines are indicated for children ages 6 months and up.

Maternal Vaccine to Protect Infants

Pfizer's RSV vaccine Abrysvo also recently won FDA approval to be used in pregnant people, to protect newborns against serious RSV-related outcomes.

ACIP has yet to issue recommendations on how to use the vaccine, but the FDA approved the shot for pregnant people at 32 to 36 weeks' gestation, given the possible risk for preterm birth.

There was a numerical imbalance in preterm birth in the vaccine group compared with placebo -- 5.7% versus 4.7% -- and the FDA included a "warning to inform" about this difference in the vaccine's prescribing information.

GSK in this population due to an .

Support for Abrysvo in this population comes from the , which included about 7,000 pregnant patients. The vaccine had 81.8% efficacy against severe lower respiratory tract disease in infants within 90 days after birth, and 69.4% efficacy within 180 days after birth.

In a subgroup of about 3,000 pregnant people who got the shot at 32 to 36 weeks' gestation, the vaccine reduced infants' risk of any medically attended lower respiratory tract disease by 34.7% within 90 days and 57.3% within 180 days. Risk for severe lower respiratory tract disease was reduced by 91.1% and 76.5%, respectively, .

FDA is requiring Pfizer to conduct postmarketing studies to assess risks of preterm birth and hypertensive disorders of pregnancy, including preeclampsia.

Since both the maternal vaccine and the monoclonal antibody for infants are approved, experts noted that these young children don't need to get both.

"In general, the discussion is that it wouldn't make a lot of sense for most infants to have gotten both," O'Leary told 麻豆传媒. "So if the pregnant person gets the vaccine during pregnancy, and there's a healthy term newborn, you wouldn't recommend nirsevimab for that baby."

An exception might be if the pregnant person delivered within a few days of getting the maternal vaccine, O'Leary said: "That's not enough time for the infant to get the benefit."

He added that there's no harm if an infant does end up getting both, though. "There's not a concern for safety," he said. "It's just that the incremental gain you would get for getting both is pretty darn small."

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