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Advisers to the U.S. Food and Drug Administration (FDA) on Thursday recommended approval of AstraZeneca’s new monoclonal antibody, which the drugmaker said is designed to protect infants and toddlers up to age 2 from respiratory syncytial virus (RSV).
The drug, nirsevimab, would be delivered to newborns in a single shot at birth or “just before the start of a baby’s first RSV season, or as a larger dose in a second RSV season in children who are highly vulnerable,” CNN reported.
Members of the independent committee, which includes several pediatricians, “were enthusiastic about the potential” of the antibody, STAT reported, as was Thomas Triomphe, executive vice president of vaccines at Sanofi, which will market the drug in the U.S.
In a statement, Triomphe said:
“Most babies hospitalized with RSV are born at term and healthy, which is why interventions specifically designed to protect all infants are likely to result in the greatest impact.
“We are encouraged by the advisory committee’s positive vote based on the compelling clinical development program supporting nirsevimab and its breakthrough potential to reduce the magnitude of annual RSV burden.”
But medical experts interviewed by The Defender raised a number of concerns, including what they said was inadequate safety testing.
“It’s preposterous to give this drug prophylactically, especially without adequate safety testing,” said Brian Hooker, Ph.D., P.E., senior director of science and research for Children’s Health Defense (CHD).
AstraZeneca reported only 48% efficacy for the drug. And Hooker noted that the “circulating half-life of the antibodies is probably less than one month so the protection would be minimal at best.”
Hooker also commented on the fact that 12 infant deaths were recorded during the clinical trial, which the FDA committee claimed were “unrelated” to the antibody:
“It appears that this vote was meant to bolster uptake and popularity of the RSV vaccines that are now approved for maternal use. The very low rate of effectiveness for such a therapy is troubling as the conservative estimate is below 50%, which is usually a hard metric for drug approval.
“Also, it seems odd that four infants in the trial would die of cardiac arrest — with no information given, it leaves one to wonder why these children would die in such a way. Also, there should be further investigation into the two SIDS [sudden infant death syndrome] deaths that occurred during the trial.”
Dr. Meryl Nass, an internist, biological warfare epidemiologist and member of CHD’s scientific advisory committee, told The Defender,“It is reckless in the extreme to inject very young babies with an inadequately tested monoclonal antibody drug to prevent a condition that for most of them will be no more than a cold.”
Cardiologist Dr. Peter McCullough told The Defender that while monoclonal antibodies are “generally safe” for children, he questioned the benefit of such a treatment for what he called a “mild” infection. He said:
“Monoclonal antibodies are generally safe in children and adults; however, I am concerned broad infant population uptake may disrupt normal thymus and immune system development that easily handle infections such as RSV, influenza, rhinovirus, adenovirus and SARS-CoV-2.
“RSV is a characteristically mild infantile infection easily resolved with conventional nebulizers. I believe nirsevimab would not be clinical-indicated for all infants and likely would be utilized in high-risk babies with congenital heart or lung disease, such as cystic fibrosis, or those with prior thoracotomies for heart surgery, where respiratory mechanics would be compromised.”
The FDA committee’s positive recommendation for nirsevimab, also known as Beyfortus, comes just weeks after the agency approved GlaxoSmithKline Biologicals’ Arexvy, the first-ever RSV vaccine for older adults, and recommended Abrysvo, Pfizer’s RSV vaccine for pregnant women.
According to CNBC, the FDA is expected to make a final decision on nirsevimab in the third quarter of this year.
Nass told The Defender that while the FDA is not obligated to follow the panel’s advice, “it almost always does so.”
FDA: Infant deaths during clinical trial ‘unrelated’ to the treatment
CNBC reported that the FDA review identified no safety concerns with nirsevimab, but also reported that 12 infants died during the trials.
According to CNBC:
“Four died from cardiac disease, two died from gastroenteritis, two died from unknown causes but were likely cases [of] sudden infant death syndrome, one died from a tumor, one died from COVID, one died from a skull fracture, and one died of pneumonia.”
Dr. Melissa Baylor, who according to CNBC is “an FDA official,” said, “Most deaths were due to an underlying disease. None of the deaths appeared to be related to nirsevimab.”
But according to STAT, “There are questions that remain to be answered” about nirsevimab that require “further study.”
For instance, no data are available “about whether giving nirsevimab to a baby whose mother was vaccinated against RSV during pregnancy would give the infant more protection or would be a waste of the product.”
STAT noted that several members of the FDA committee “worried that the dose given in the first year of life might be too small to benefit a baby who was 8 months or older when receiving the injection, depending on the size of the baby.”
Baylor also expressed concerns about how nirsevimab would interact with vaccines in development — such as Pfizer’s Abrysvo — that confer protective antibodies to the fetus by administering the shot to the mother.
CNBC reported that “Other monoclonal antibodies have been associated with serious allergic reactions, skin rashes and other hypersensitivity reactions.”
According to Baylor, the FDA did not identify “any cases of serious allergic reactions in the nirsevimab trials,” while “cases of skin rash and hypersensitivity reactions were low in infants who received the antibody.” She added that cases of such side effects are expected to be observed if the treatment receives FDA approval.
Manish Shroff, AstraZeneca’s head of patient safety, said, “Safety is of utmost importance” to the drugmaker and that it will “keep a close eye” on the safety of nirsevimab via a “global monitoring system,” CNBC reported.
According to Endpoints News, nirsevimab has already received regulatory approval in the EU, U.K. and Canada, but “it has not yet launched in any of those markets.”
According to CNBC, “Nirsevimab is administered as a single injection with the dose depending on the infant’s weight.”
Infants weighing less than 5 kilograms will receive a 50 mg dose for their first RSV season, while those over 5 kilograms will receive a 100 mg injection. Children under age 2 who “remain at risk for severe RSV” in their second season would then receive an additional 200 mg injection of the antibody.
Nirsevimab is not the first monoclonal antibody for RSV. According to STAT, AstraZeneca’s Synagis (palivizumab) is approved in the U.S. and EU, and “protects against infection in high-risk infants.”
According to CNBC, it is intended “only for preterm infants and those with lung and congenital heart conditions that are [at] high risk of severe disease” and is administered monthly, whereas nirsevimab “would be administered to healthy infants.”
Endpoints News reported that “AstraZeneca leads all development and manufacturing activities” for nirsevimab, “while Sanofi is responsible for marketing activities and revenue recognition” — for which the drugmaker paid $129 million “to be part of the collaboration.”
Is RSV really a danger for most infants?
CNBC previously reported that the U.S. “suffered an unusually severe RSV season” this past winter. The New York Times reported on a “tripledemic” involving RSV, flu and COVID-19, “that swamped children’s hospitals and some I.C.U. wards.”
One U.S. county — Orange County, California — declared a local health emergency and issued a proclamation of local emergency in November 2022, citing rising RSV cases among children in the region, and the Biden administration subsequently declared a public health emergency that month.
According to the U.S. Centers for Disease Control and Prevention (CDC), nearly all children are infected with RSV before the age of 2.
While CNBC characterized RSV as a “public health threat” that “kills nearly 100 babies in the United States every year,” Nass questioned the danger it poses to most infants.
In May, Nass wrote that the CDC published a paper on RSV deaths in infants between 2009 and 2021, which found “were only a total of 300 deaths in children less than one year over the 12 years, or 25 on average per year.”
Nass added that the number of injuries that may be caused by vaccines or other treatments during pregnancy “is almost certainly going to outweigh the loss of 25 babies a year from RSV.”
In her remarks to The Defender, Nass drew comparisons with the hepatitis B vaccine for children, saying that adverse effects from the treatment may appear later in childhood and are not likely to be connected to the drug:
“The hepatitis B vaccine, recommended for all children at birth in the US, and received by about 75%, was never tested for babies’ safety — over more than a few days — before the program started, or since.
“Because no one can know what a very young baby will become at birth, it is impossible to attribute a lower IQ, hyperactivity, less nimble limbs or any other problem that shows up later, to an injected drug given shortly after birth. So those connections, if any, are unlikely to be identified.”
