Discussing FDA-approved nirsevimab-alip for RSV prevention

On July 17, 2023, nirsevimab-alip was approved by the FDA to prevent respiratory syncytial virus (RSV) in neonates and infants born during, or entering their first RSV season, and for those up to 24 months that remain vulnerable to severe RSV amid their second season. In this Contemporary Pediatrics® interview, John Bradley, MD, medical director, infectious disease, Rady Children's Hospital, San Diego, California; professor of pediatrics, UC San Diego School of Medicine, explains how the approval will impact this patient population.

Transcript (edited for clarity):

Contemporary Pediatrics:

Thank you so much for joining us. I'm Joshua Fitch of Contemporary Pediatrics.

John Bradley, MD:

Hi, I'm John Bradley, the medical director of infectious disease at Rady Children's Hospital and a professor of pediatrics at the University of California San Diego School of Medicine.

Contemporary Pediatrics:

Dr. Bradley, thank you so much for joining us and being here. After receiving support from the FDA Antimicrobial Drugs Advisory Committee, nirsevimab has been approved by the FDA to protect infants born during or entering their first RSV season. Dr. Bradley, your initial reaction to that news.

Bradley:

I'm very pleased with this.and it's because RSV creates an enormous amount of illness and respiratory distress difficulty breathing in babies during their first year of life. And to have something that will prevent that or modify it is incredible. We hospitalized almost 1000 babies last year, both well [healthy] babies, as well as babies with underlying heart disease or lung disease who had RSV pneumonia. If nirsevimab in clinical practice, meets its expectations, we should decrease the number of hospitalizations from 1000, down to 500, or even 300 or 400 per year, which is which is a dramatic decrease. Something that anyone who takes care of these babies can appreciate is that this viral pneumonia in small babies creates so much inflammation, pretty characteristic, that huge amount of mucus production, the lungs become very sticky, and these babies can't breathe. And they know it. A six-month-old, who can't get their breath, you just look at them and you know they're struggling. These are babies whose parents are obviously incredibly worried about them, they bring them to the doctor to the emergency room urgent care, they get admitted to the hospital with oxygen. For most babies, you just need to support them with oxygen for a few days, knock out some of that mucus, which we can do better in the hospital with all of our resources, and then they do fine. But it's those few days of terror for the parents and anxiety for the doctors and nurses who perceive them and are taking care of them that is profound. [Healthy] babies, every child can get into trouble with pneumonia because their lungs are immature, and they just can't expand very well. So, to have that decreased by over 50% hospitalizations and clinic visits is a small miracle.

Contemporary Pediatrics:

Thank you, Dr. Bradley. Of course, RSV is the conversation in pediatric care every year. With a unanimous vote of 21 to 0 for the support of this favorable benefit risk profile for the first RSV season; obviously the numbers sort of speak for themselves in that regard related to the FDA. Can you break them down a little further though, and maybe explain why it was a unanimous vote of support?

Bradley:

Well, I can certainly share with you why so many people were in favor of this, and it has to do with the balance of benefits and risks. With every drug that this committee views and contemplates and makes a suggestion to the FDA, what you always have to do is look at benefits and risks. So what is striking about this drug is how safe it was. You could almost not find any safety signal and nirsevimab-treated babies. The drug was very well tolerated, no allergic reactions. None of the severe anaphylaxis reactions that you might get. When you look at at that kind of safety record, and you look at decrease in the severity of disease, decreasing medically attended visits by over 50 to 75%, you clearly should vote in favor of recommending for approval. Many of the people on the committee have taken care of babies with RSV, and it's very frustrating to try and manage these babies. What you can do with nirsevimab is make these babies far less sick. So it's not a treatment of the infection, it's prevention, knowing that they'll all get exposed, and it modifies the disease severity, so that they have much milder disease that they can manage. Winters will be much more easily tolerated by both parents and the medical community in the future.

Contemporary Pediatrics:

You kind of touched on it already, it's multifaceted this approval, how crucial is it on those many different levels, not only from the infant, the parents, and even the healthcare space? You mentioned this potential reduction in cases. What can that say just from a healthcare setting perspective?

Bradley:

As a pediatrician, my life's work is to minimize suffering and death in children from infection. So, RSV as a virus doesn't destroy lung doesn't cause the kind of intense rapid inflammation that influenza does. I think people have been less driven to try and come up with preventive medicines or treatment medicines for RSV, because it's just a really bad chest cold. And if you're not a parent, and the fact that babies really aren't dying, there's only 100 deaths in the United States per year, which is, depending on how you look at it, 'oh, my, it's 100 deaths per year.' But it's far less than many of the bacterial infections that babies can get. It’s not so much of a lifesaving drug but is going to save tremendous suffering in these babies. All you need to do is to see a few of these babies just gasping for air, and as a parent having this kid at home, you need to figure out when you need to take your baby to the doctor. These babies have such a hard time breathing, you have this fear that they can stop breathing at any moment and die on you. I don't know that I'm exaggerating for the severity of disease that we see in kids in the hospital, because boy, they really do need oxygen. Some of them need positive pressure, we put special masks on them to increase the ability of pushing air into the lungs and opening up all those sticky airways. So that's something that we can do. Once these babies get their airways open, and they can breathe, they're fine. They start smiling, you can distract them with stuff, and you can interact with them. But before you put the oxygen on, when you check their oxygen levels with our monitors, they get down to dangerously low levels. These babies know that they're suffocating, basically, with this virus. They can't get enough oxygen into their bloodstream, their brains know it and the anxiety you see on their faces is very clear, and the parents very clearly pick this up. So, it's the suffering side of the equation. From the pediatric infectious disease standpoint, knowing that RSV is the most common cause of hospitalization in babies, this virus pneumonia, and we're going to cut it by at least half is incredibly important.

Contemporary Pediatrics:

Dr. Bradley, one more for you. Is there anything else you would like to add on this FDA approval?

Bradley:

What I think is is very important and striking about this particular drug and this particular approval is that for the first time, we have a monoclonal antibody, not a vaccine. The outcome is the same you protect children from infection, but for the first time, there's a monoclonal antibody that will be recommended to virtually all babies born, particularly those during or just before the RSV season. That is such a profound recommendation with such a profound impact on on all pediatric health care providers, that I have to step back and recognize just how significant this event is. So just like, you know, when you take your baby to the doctor you get you get all of the shots for prevention of disease that have been very well studied and validated that they prevent disease. Now, in addition, you'll get a single shot of nirsevimab to prevent serious RSV infection during that first year of life, and for those babies who have underlying lung and heart disease, which makes them at particular risk, with stiff lungs to get into trouble with RSV pneumonia, the drug's also approved for the second year of life for those high risk infants whose hospitalizations tend to be not just overnight, but for for a week or two as they get over their illnesses. So, the broad reach of this particular monoclonal antibody over the entire population of newborn infants is quite profound.