Narrator - Dr. Abel  00:00
Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast is

Speaker 1  00:12
provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy.

Narrator - Dr. Abel  00:17
This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. And now on to the show.

Dr. Sean Kane  00:33
Okay, welcome to HelixTalk. Episode, 171 I'm your co host, Dr. Kane, and I'm Dr. Patel, and the title of today's episode is two vaxes and a Mab. What's new in RSV prevention? And I'm very excited to have a special guest with us today. Dr. Lauren Angelo, who's a regular contributor on HelixTalk. Dr. Angelo, could you just briefly introduce yourself to the audience and why you're here today? Absolutely.

Speaker 1  01:02
Hi, Dr. Kane. Hi Doctor Patel. This is such a hot topic, so thank you for inviting me. Ever since we started getting information around these RSV vaccines coming to market, it's just something I've been paying attention to. So I feel like this is great timing in terms of what we have to convey to our audience, and I'm always passionate when it comes to vaccine topics. So without further ado, let's get on to it.

Dr. Sean Kane  01:27
So Dr. Angelo, I want to kick things off by probably the most important question that our listeners are going to have when it comes to RSV, and that is, how do you pronounce the word that the S is in RSV?

Speaker 1  01:40
That is a great question, and one that I have struggled with. And so I came across a website that helped describe how to pronounce it, and it's like the word initial, so we would say respiratory syncytial virus, RSV, perfect.

Dr. Sean Kane  01:56
Our TED talk is over. Thank you for joining us today, in all seriousness in terms of RSV, so this is a cold type virus. What are some of the symptoms associated with RSV, and why do we need a vaccine for it, if it is just giving people cold like symptoms?

Speaker 1  02:12
Yeah, great question. Most people who get RSV might not even know that they have RSV. It tends to look like a cold. You might have a runny nose, cough, sneezing, fever, maybe loss of appetite, feeling a little tired, and maybe dehydration could start to occur and and again, for most people, they recover over one to two weeks. It's what happens to the individuals who end up with severe respiratory symptoms. So it transfers over to lower respiratory tract disease, they start to present with wheezing, difficulty breathing, and that can turn into bronchiolitis and pneumonia. The individuals who are most at risk for severe RSV are going to be our very young children, as well as our older patients and those with chronic medical conditions, which we'll get into a little bit

Dr. Khyati Patel  03:02
talking about our young patients. You know, it was up until last year. I have a, you know, four and a half year old. It wasn't up until the last year where the word was like, Oh, my God. It could be an RSV infection. Or there was a quadruple panel that was run at the pediatrician office whenever we went in with a cold, and RSV was one of them. So, you know, when we talk about little babies, right, mom and dad will have no kissing on the face policy, and that's the reason, most likely, because babies can get really sick with this. But even a little older kids can have longer lasting symptoms of cold due to RSV.

Speaker 1  03:38
It's very contagious. It's transmitted via respiratory droplets. We can also sometimes touch surfaces that have droplets on them and then transfer them to our respiratory tract. So we do have to be careful, just like we would with all of our respiratory illnesses.

Dr. Sean Kane  03:53
Just to add on to how contagious it is, according to the CDC, and I'm quoting, almost all children will have had an RSV infection by their second birthday. So think about that for a second. Almost all children in the US will have had RSV before they turn two. That is an incredible number, and it does highlight that many of those kids will just have the common cold type symptoms, but some of them will progress on to more severe symptoms as well,

Speaker 1  04:19
and they're little carriers, right? So they could give it to other people who might not be able to manage an RSV infection as well.

Dr. Khyati Patel  04:28
So what does the data look like for the adult patients with RSV? We said no cold symptoms. However, when we talk about more of the extreme issues, such as hospitalization, was what does that look like? So when

Speaker 1  04:40
we think about RSV in terms of morbidity and mortality, the data that the CDC have for us is we see about 60 to 160,000 hospitalizations each year due to RSV, and unfortunately, about six to 10,000 die each year from RSV. So again, while many experience medical. Like symptoms, there are others who then go on to have more significant impacts from RSV infection.

Dr. Sean Kane  05:06
That's an adult. What about for infants, those really young children, are they at risk for hospitalization, or is this just a severe cold for them?

Speaker 1  05:15
Children are at risk as well. It's about two to 3% of infants will require hospitalization, and again, it's when they get that severe infection leading to bronchiolitis or pneumonia,

Dr. Khyati Patel  05:28
and Dr. Angelo is the pattern for RSV outbreak. Is it more common to be around the flu season, or is it like a year or around thing like sometime covid?

Speaker 1  05:39
Is sure, at one point we thought, Yes, this is more like flu, with outbreaks in the fall, in the winter, and being able to track this annually. But as we saw with many illnesses, covid 19 has disrupted that completely. And so even the last couple of seasons with RSV, it's been a little bit off. And so that disruption to seasonality has made it more challenging to predict when we'll have peaks. So this will become important as we talk about the ACIP recommendations for when to vaccinate our older adults,

Dr. Sean Kane  06:09
then when we're thinking about, you know, who are the patients that we're more concerned about? So who are the people who are more likely to be hospitalized? What are some factors or chronic health conditions that are associated with a higher risk of having a more severe RSV infection?

Speaker 1  06:27
That's a great question, because we've talked about our young children and older adults, but in our very young children, especially if they're premature infants, they're at higher risk. In any of these populations, anyone who has immunocompromised is going to be at higher risk. But then, as we think about again, this is a respiratory illness, so across the board, who are the patients most impacted by respiratory illnesses? Those are going to be individuals with heart and lung conditions. So we think about things like heart disease, asthma, COPD, heart failure. As we add more comorbidities to that as we increase age of our patients, again, those risk factors are going to increase as well, and think about long term care facilities and nursing homes. So those are the individuals as we talk about vaccination and protecting them, those are the individuals we'll be thinking about.

Dr. Khyati Patel  07:19
And I know our episode here today is dedicated to discuss these new vaccines. But you know, question is, you're talking about people who are at higher risk and need these morbid morbidity and mortality data. But what do we do before the vaccines? You know, were there any therapies that we employed for patients who are at higher risk or who have a severe RSV

Speaker 1  07:43
disease, unfortunately, not really. We don't have antivirals for RSV. And Dr. Patel, you brought up testing of your child, we weren't really even testing for RSV. You know that wasn't as active as we are now. But as vaccines started to come about and come to market, obviously testing ramped up because we need to evaluate, are these vaccines working in our communities or not? So as we're monitoring these, you know, we're seeing, you know, different numbers than maybe we had in years past. We'll talk about a new drug called nirsevimab, or Beyfortus, that was actually approved in July 2023 it is a monoclonal antibody, but you ask what we've had previously, and there was an older monoclonal antibody, palivizumab, that's been actually on the round since the 90s, but we didn't use it as often. It was really for those less than two years of age with high risk conditions, and we had to it was an injectable vaccine that we had to give monthly over the course of RSV season. So it was a little bit challenging to give. So in July of 2023 this newer monoclonal antibody, again, nirsevimab, was approved. It's indicated for our all children less than eight months of age as they enter their first RSV season, so we can actually start to administer it in the hospital at birth, if the timing is right. So if we have a child born just before RSV season, we're going to give this monoclonal antibody to them. It'll protect them for about five months. So the hope is it will get them through that season. Then the other group that we're looking at is individuals who are eight to 19 months of age entering their second RSV season, who are at risk for that severe RSV disease. So they would also get a dose as as we would go into that season.

Dr. Sean Kane  09:34
Doctor Angela. One really interesting thing about today's episode is that summer ish 2023 was super duper hot when it comes to RSV therapies. You just mentioned a new monoclonal antibody, but just a month or two prior to that, May 2023, we had not one, but two new RSV vaccines, and we'd never previously had any RSV vaccines. So clearly, a lot of movement in. The RSV sphere. Maybe you could walk us through, especially the pronunciation, but walk us through the two new vaccines that were approved back in May of 2023 and then maybe we can go back and forth in terms of what are some similarities and differences between these vaccines.

Speaker 1  10:15
And before we even go that route, because we just talked about the monoclonal antibody, let's get into the vaccines. But I think we need to understand what these vaccines and monoclonal antibody are doing in terms of this virus. So we called it Syncytial respiratory syncytial virus, and that has to do with the spike proteins on this virus. There's a glycoprotein and an F glycoprotein. It's that F glycoprotein, it's causes the cells to fuse, and this is what results in clinical disease. And so this fusion is called syncytia, and this is how RSV gets its name. So as we talk about the monoclonal antibody, as well as these new vaccines, Dr. Kane that you've brought up, they are targeting that F protein, so it's unique. That's not something we've had before in terms of virus prevention. So I think as we sort of watch the market and how things unfold, we might see more of these come about in terms of just where, where they're working in the RSV space. So the two vaccines that we have, we've got something called Abrysvo, that one's made by Pfizer, and we've got something called Arexvy, and that one is made by GSK. They both are considered this pre F and so it's looking at a pre fusion F protein vaccine. So again, getting back to that prevention of that that F protein causing the fusion of those cells. It's intramuscular injection, like we see a lot of vaccines, it's inactivated. We're going to give a half a milliliter as we inject that they are needing to be reconstituted, and we must use them within four hours of reconstitution. So I always encourage anytime we have to reconstitute a vaccine, we need to look up that time window of when we have to use it. The refrigerated vaccines, both of them, the difference, though, is in terms of how they're prepared. So while they are both these lyophilized powders and they have a diluent, the steps for a brief spell are a little bit unique. So I would encourage users to refer to the package insert on how to reconstitute that, reconstitute that vaccine. You've got a syringe and a vial adapter that's provided that you need to use for that reconstitution.

Dr. Khyati Patel  12:24
And I think the similarities of the two vaccine is great, but some of the differences are important to highlight as well. So for Abrysvo, it contains two different recombinant proteins. So as Dr. Angela you mentioned, these are the pre F protein. So this one includes the A and the B. Basically, they're viewing this as like two different variants. So you can say maybe this is a bivalent that covers that protein A and protein B. And so one, one trick to remember this, if this is bivalent, quote, unquote Abrysvo has the B in it. So B stands for bivalent, something like that.

Dr. Sean Kane  13:03
Dr. Angela, how does our vexi compare to that in terms of what's in the laugh lies file in terms of the ingredients,

Speaker 1  13:11
absolutely so. Dr. Patel, you did a great job summarizing Abrysvo in this quote, unquote, bivalent approach using the A and B components. Arexvy is a little bit different, so it has a recombinant protein plus an adjuvant. So we've started to see more adjuvanted vaccine. Now, if you recall, this is made by GSK. GSK also makes shingrix, and interestingly, they've used the same adjuvant that we see in the shingrix vaccine, but it is half the amount. And so one way, it's kind of silly to remember, or at least in my brain, how I remember the differences between the two. I say Arexvy is adjuvanty.

Dr. Khyati Patel  13:49
That was great to kind of have an overview of both of these new vaccine. Dr. Angelo, can you explain the audience, like, how is the initial approval from the FDA and how ACIP is weighing in as to how they should be used for what patient population, sure.

Speaker 1  14:07
So the manufacturers, as they were working on the clinical trials for these vaccines, were really focusing on our older adult patients. So when they took the data to the FDA to get approved, this was for adults 60 years and older, and it was to not to prevent RSV necessarily, because it's really difficult to prevent a respiratory infection from entering a respiratory virus from entering our bodies and causing infection. A lot of times with respiratory diseases, these vaccines focus on preventing severe disease, and so in this case, it's preventing RSV associated lower respiratory tract disease, and that's what they are approved for. And then a couple months later, and then these manufacturers, because of that time frame, had more data to share. They went to ACIP to get an ACIP endorsement of the FDA approval. And so the FDA looked at. Some of this newer data, and they agreed with the age group, and so they did recommend this vaccine for 60 years and older. However, they added that it needed to be under the shared clinical decision making model, and this is we've seen this with other vaccines, where we as providers need to be flagging patients who might be good candidates, but then having a conversation with them regarding the risks and benefits of vaccination, and the ACIP has done a great job of sharing with us which individuals to consider for that vaccine under that shared clinical decision making approach, and those are going to be our higher risk patients with heart and lung disease, maybe those who are immunocompromised as well, and so they've got a pretty long list that they provided in their recommendations. And so we would just use that as we're having those conversations I mentioned earlier too, about the timing, and Dr. Patel, you'd asked about the seasonality, and can we predict that? And so these recommendations were made over the summer as we're entering the fall season. So ACIP said, Okay, as soon as the vaccine supply becomes available, start offering vaccination to those eligible adults. Keep vaccinating anyone who remains unvaccinated, and don't worry about the time of year again, because we can't predict the seasonality. We'll just go ahead and vaccinate anyone who's not vaccinated, regardless of time period.

Dr. Sean Kane  16:26
And it's always interesting, Dr. Angelo, how the FDA may have slightly different recommendations or slightly different approval criteria between FDA and ACIP. I did mention earlier in the episode that you know summer 2023 is super hot with RSV right now. And another big news item was actually in August of 2023 a new FDA approval for a brief vote, the Pfizer vaccination. Could you tell us about that new FDA approval?

Speaker 1  16:55
Yeah, so you know we think about, and I want to back up a little bit to our Tdap vaccine, and that covers tetanus, diphtheria as well as pertussis. For years ago, we started offering Tdap to women who are pregnant to protect the newborn baby from pertussis. And so it was transferring that that passive immunity from mom to newborn, because that newborn was too young to be vaccinated against pertussis, but yet had high risk for getting pertussis and severe illness and death from them. So following a similar model, we're looking at using this RSV vaccine in pregnant women, not to protect the woman so much, but to protect the newborn. And so this particular recommendation as it came out and got the FDA approval was for pregnant individuals at 32 to 36 weeks gestational age. And again, we're preventing lower respiratory tract disease due to RSV in infants from the moment they are born up through six months of age. And so again, that got the FDA approval. We're waiting on the ACIP review of all of this, so that meeting should happen soon. They'll either have a special meeting, or we'll wait till October, which is really just about a month away, to look at some of that data. Part of that discussion, there's been a very common question I've gotten asked now numerous times is okay. We have a monoclonal antibody, nirsevimab, that just got recommended for infants before entering their first RSV season, but now we're vaccinating mom if she's pregnant before baby is born, to protect baby. What do we do under those circumstances? And so we don't know yet, but when ACIP talked about this at their summer meeting, they're thinking that, well, if mom got vaccinated, we don't need to necessarily vaccinate that newborn child, unless there were circumstances where we don't think that vaccine will have the effect that it needs to have

Dr. Khyati Patel  18:58
Doctor Angelo. That was a that was great to lay out the land for what it is FDA approved for, and how ACIP is reviewing all these vaccines but you know, for for any agent that is approved, we always go off of clinical data and so kind of digging more into what is the, you know, clinical evidence For both of these vaccine. So Abrysvo had a study named Renoir study. Apparently, this was based off of a French artist. We are running out of clinical names, so we are going after artists and then a little bit of a lackluster or Rex, we JSK couldn't come up with a better name, but it was the AReSVi-006 study, and so Dr. Angelo, if you can just kind of summarize the similarities between these studies and kind of reviewing the differences and what clinical data was considered by FDA and approving these vaccines,

Speaker 1  19:58
sure, and I do want to make it. There that this not this is not necessarily the data that was shared with ACIP in the summer. This is what when you open a package insert for both of these vaccines. These are the trials that are noted within that package insert that that particular data was shared with the FDA for that approval. And so, as we talked about earlier, they both, both manufacturers are looking at adults who are 60 years of age and older, they did not include immunocompromised patients. And that's an important point, because we know that immunocompromised patients are at high risk for severe disease, and in fact, ACIP addressed that and said, we're still going to include that in the shared clinical decision making model for our individual six years of age and older, even though it wasn't studied. So that was interesting too, to see ACIP kind of tap into that both publications and trials were published in the New England Journal of Medicine. But again, these were interim analyzes. We're still, I think, too early on in our experiences with RSV. As we get through another season, we'll have more data. So I think all of us need to kind of be watching for that, to see what happens in terms of vaccine efficacy and effectiveness as we move forward post marketing. So they were looking at, you know, as they're they're watching for RSV, confirmed by PCR testing, but also did they have signs of illness? And so with these studies, they had to at least have two signs or symptoms of RSV and following those patients for about seven months, and there were some subgroup analyzes that were done, it was just again, kind of early on in the RSV season, plus we had covid 19 occurring, and a lot of our other disease transmission, and numbers were down because people were staying inside. They were masked. And so very hard to draw a lot of conclusions that early on. So we'll know more. I think as we go forward into this rsvcs as well as next year,

Dr. Sean Kane  22:01
maybe we can just talk about the individual trials briefly. So the first one is Dr. Patel. Mentioned was a Renoir study. This is the Pfizer product, and this one enrolled 35,000 patients. And somewhat not unexpectedly, the rate of RSV infection causing the symptoms was fairly low. So out of the 35,000 patients, 44 tested positive for RSV and had at least two symptoms of RSV infection, with 11 cases in the vaccine group, 33 in the placebo group. So this particular vaccine efficacy in the New England article, which is referenced in our show notes, showed a vaccine efficacy of 67% however, Dr. Angelo, maybe you can just briefly comment on what you mentioned earlier, that you're going to see different vaccine efficacy numbers depending on where you're getting your data from. Is that correct?

Speaker 1  22:52
It is. You know, I was looking a lot at, not these trials, necessarily, but I was pulling the slides from the ACIP meeting, which is really cool. If we can do that. We can go to the ACIP meeting website. You can see their agendas for upcoming meetings. You can look at minutes, but those take a while to post. But what I think is more interesting is you can pull the slides that were shared and even watch some of the recorded sessions and look at their data in terms of what manufacturers and others are presenting to ACIP. So with the two different vaccines, I know you know what you shared was one number, but what was shared with ACIP for these, they were looking at different seasons, and this was just based on one dose. The obese vote trial had about a little over 36,000 participants, and the orexp trial had about 25,000 participants in that first season they were looking at, and so they looked at season one post vaccination of that one dose. They also had in term analyzes for season two. They also combined season one and season two. You know, if you had one dose, how did it fare? But what I really like to look at right now is just the season one data. I think it's too early to make that jump, and that's just my opinion. But to look at season two, or combining the data for seasons one and two, I think it's a little bit messy. So when we look at just season one, and this is the vaccine efficacy against preventing lower respiratory tract disease due to RSV, both of them were kind of in the 80% zone. We saw Abrysvo was around 88.9% and then Arexvy was 82.6% so again, kind of early, little bit soon to tell, but a little bit better number than, I think, what was originally presented for FDA approval.

Dr. Sean Kane  24:42
And even if you look at the New England publication, they did describe vaccine efficacy in a variety of different ways. So instead of having two symptoms, if you had to have three symptoms or signs of RSV infection, in that publication, the vaccine efficacy went from 67% with two symptoms. Signs all the way up to 86% so certainly you're going to see a variety of different vaccine efficacy numbers between how they defined the endpoint, whether it was the interim analysis, versus what was presented at ACIP and things like that. Dr. Angelo, from a side effect standpoint, I was actually pretty surprised in the Renoir study of kind of how tolerable this vaccine was. You do have what you'd expect, which was kind of the local injection site reaction, pain, swelling, redness, things like that. But for the most part, we did not see very much in the way of systemic side effects like fatigue, headache, things like that. We're talking maybe one or two percentage points different between placebo. Really not a big deal from that standpoint, but all medications do have side effects. So were there any kind of unexpected or more rare side effects that were signals? Is something we might want to see analyzed in a phase four environment.

Speaker 1  25:55
Yeah, and I agree with you. You know, when you're counseling patients who are asking about these vaccines, really, it's expecting that injection site pain, like we do with other vaccines, and then maybe those mild symptoms like headache and fatigue afterwards. Remember, we do have that adjuvanted vaccine available as well from GSK, and we don't have a lot of data around this, but when you think of an adjuvanted vaccine, sometimes you can think there might be slightly higher localized effects from that vaccine, maybe some systemic effects, more so than the other, but time will tell, as we watch those on the market. What was interesting, though, Doctor Kane, you asked about some of these unexpected adverse events, and this actually happened with both different vaccine manufacturers. One of them was atrial fibrillation, which I think was unexpected. And each now remind remember, there were, what did I say, about 37 and 25,000 participants in each respective trial. So these numbers are very low, but they did result in a signal and something to watch further. So each manufacturer reported 10 a fib events in the intervention group and four in the control group. So it was still happening in control but there was a little bit more in the eight in the intervention group in terms of a fib, and this had occurred within 30 days of vaccination. So that's one thing we're probably going to keep watching and keep our eyes on. The other one that was interesting was what we're calling inflammatory neurologic events. So think of Guillain Barre Syndrome, which we've heard about. You can get that just from a viral infection, but we have heard that with other vaccines, and so watching for GBS, and some of these GBS, like events, there were six cases reported across both studies. So again, very low numbers, but definitely something that was interesting, and we'll keep watching that as we move forward.

Dr. Khyati Patel  27:56
Dr. Angelo, that was great to kind of get those nuanced side effects like AFib or Guillain-Barre syndrome. But Dr. Kane, I think you wanted to mention sort of a difference between the two vaccine, particularly when it comes to their systemic side effect, and that's stemming from the differences between the two vaccines. Yeah.

Dr. Sean Kane  28:17
So Dr. Patel, in our second study, the GSK product, Arexvy, we actually saw a much higher incidence of the systemic side effects, so we're thinking fever, headache, myalgia, fatigue, arthralgias, instead of maybe one or 2% point difference between placebo and the vaccine, we saw, in some cases, double or even higher in terms of the systemic side effects. And again, this is with the adjuvanted Arexvy versus Abrysvo, with the Pfizer vaccine that is not adjuvanted Doctor Angelo. Is this what you would expect in terms of, would you expect that an adjuvanted vaccine would have more systemic side effects than a non adjuvanted vaccine, it

Speaker 1  29:03
is, and I think we do see that in practice as well. I brought up earlier that this is the same manufacturers of shingrix, and we do see that with shingrix too, as an adjuvanted vaccine, they are known to be more reactogenic. We see that with our influenza vaccines on occasion as well. And so I would expect some of those side effects to be more pronounced in the vaccine recipients, as opposed to the placebo recipients, because of that adjuvant that's prompting the immune system to respond. But in doing so, that reactogenic effect does sometimes cause our bodies to say, Okay, there's something going on here, and we tend to see more of those systemic and localized reactions.

Dr. Sean Kane  29:47
But then I'd say overall, from these two studies, this is what really led to ACIP recommending to vaccinate those 60 years of age or older, using shared clinical decision making. And I think one. Reason, potentially, why certain areas maybe are having a more lukewarm response to the RSV vaccination is the number needed to treat in both of these studies is pretty high, so depends on what endpoint you're looking at, but we're looking at several hundreds, number needed to treat, so something like 200 to 400 again, these were very large trials, and we saw fairly low incidence of RSV with an asterisk that this was during a time that we actually didn't see a ton of RSV infections. We'll talk more about that later. So you know that is kind of how vaccines work, though. Dr. Angelo, is that correct in that we're expecting to vaccinate a large population in hopes that we prevent disease in a fairly small population. Correct?

Speaker 1  30:44
That is true. And I think when we look at why ACIP made the decision they they did in terms of shared clinical decision making and really asking us to focus on those high risk groups, that's probably why. You know, we don't have necessarily a ton of data that says absolutely everybody needs this vaccine. It's really focusing on who's going to most benefit from it, and you know, the number needed to treat. You know, tells an interesting story.

Dr. Khyati Patel  31:12
These two data that we discussed were for patients who are 60 years and older. We kind of mentioned earlier that our bresbo recently received an FDA approval for use in pregnancy during that 32 to 36 weeks in gestational a. CIP hasn't weighed at weighed in on this approval just yet. But if we were to just quickly summarize, you know, what were, what was FDA looking at what trial information and clinical data was FDA looking at for this particular patient population, sure.

Speaker 1  31:48
And again, this was the Pfizer vaccine, specifically. And I think this is another French word, so it was the Matisse study, named after Henry Matisse, a French artist. So Pfizer coming up with that name as well. They were looking, in total, this is Dr. tell you mentioned 32 to 36 weeks, but the study was actually in 24 to 36 weeks, gestational age, and just looking for medically attended RSV, lower respiratory tract infection, and looking at different endpoints in terms of severity, and they were looking at time points as well. So the goal again being to protect the newborn, so they would monitor the newborn for those infections, not not mom. So looking at the new baby get an RSV infection that involved the lower respiratory tract. And so looking at 90 days, 120 150 180 days after 180 days after birth. So they had about 7000 women enrolled in the trial with a similar number of infants once they gave birth. But then, as we get into what the FDA looked at, it was really based on a subgroup analysis of about 3000 women. And that's what, where they narrowed down that window and found that the vaccine was more effective in that 32 to 36 week time period. So they narrowed that and it'll be interesting to see what ACIP ends up doing. They obviously were looking at the original question and trial data of 24 to 36 weeks, and are they going to come out with a more narrow window? My guess would be yes. I mean, that's when you look at the package insert, what's what's been approved. So I would think it would be the same in terms of that time period, but, but we don't know yet, so we'll keep an eye on that in the

Dr. Sean Kane  33:40
Matisse trial globally, and again, this is going to be the entire population, not just that subgroup. With the later gestational age we saw for severe RSV lower respiratory tract infection as an endpoint, the vaccine efficacy was pretty good. So we're looking at 70 to 80% depending on what time period you're looking at. So they looked at that endpoint at 90 120 all the way up to 180 days after birth. They also looked at any severity of RSV lower respiratory tract infection, and the vaccine efficacy was lower. We'll call it like mid 50s. And in the trial, very often, we'll look at the lower bound of of the confidence interval, in this case, a 99.5% confidence interval. And that lower bound was too low. So because of that, that did not meet their threshold for success. Secondary endpoints. They looked at RSV hospitalization early on, so like at 90 days post birth. Vaccine efficacy was pretty good at 68% but then they kind of lost statistical significance as time went on, probably as the vaccine effectiveness wore off, and by one year out of birth, the efficacy was really not there anymore.

Speaker 1  34:47
And I think we're only looking at probably good six months worth of protection, because it is that passive immunity. It's not active immunity, and we know that's relatively short term. And so we're going to make sure we. Get that that child protected in those earlier months of life.

Dr. Khyati Patel  35:05
And also important to look at the safety data when we are giving it to pregnant mothers in terms of, you know, injection site and pain and redness were noticed just like the Renoir trials, the systemic events weren't that really different between the two groups, placebo and the intervention. And most importantly, you know, in pregnant patients, we look at if the medication or intervention ends up affecting pregnancy related outcomes, and they did not notice any pregnancy related complications. Some examples can include premature delivery or low birth rate, but none of these were noted.

Speaker 1  35:44
And I think the one thing with all of those, Dr. Patel that we'll probably keep our eye on is that premature or preterm births. We did see GSK working on their trials as well, but they ended up stopping them early because there was an imbalance in preterm births in their particular trials in low and middle income countries. So as we move forward with this, the use of the Pfizer vaccine post marketing, that's something obviously that is very important to keep our eyes on and to report out, obviously, any issues post vaccination that are discovered.

Dr. Sean Kane  36:18
So to kind of conclude the use of this vaccine in pregnant women, we definitely see efficacy, pretty similar efficacy, depending on what time point you're looking at to Renoir. But one interesting thing, we didn't get too much into the data, the RSV infection rate among these newborns was actually much higher than the RSV infection rate among that 60 plus year old patient population. So that actually bodes well in terms of a more favorable number needed to treat. And I want to caution the audience a little bit of getting too worked up about the number needed to treat, or the relatively low number of RSV infections. And it really deals with when these trials were conducted with respect to covid and also with respect to the RSV prevalence during that time. So, Dr. Angela, would you mind just briefly mentioning, like, what was typical RSV prevalence then versus now? Was this an abnormal time because of covid? What can you share with us?

Speaker 1  37:17
Yeah, we saw with, you know, we saw it with influenza as well during, you know, that high peak of covid, right? You know, in that summer and going into the 2020 2021, season, your dad is almost too low to do anything with. And so if they were running trials during that time period, it's very hard to track as we kind of came out of the, you know, high part of covid, and we've relaxed our mask wearing, and we're out in public, more infections tend to spread. And so we saw that with RSV as well. And so looking at some of that tracking that the CDC offers, the rates in fall of 2022 so just a year ago, were much higher than we've seen in past several years. So again, we'll have more data, I think, as we move forward in terms of that efficacy and effectiveness of these vaccines, it's just at the time point when these went to the FDA, when they went to ACIP, they just didn't have as much to work with.

Dr. Sean Kane  38:17
For the audience, if you're curious, the CDC actually has an RSV net interactive dashboard where you can actually look to see RSV rates over time at different seasons and absolutely fall 2022 was way, way, way higher than it was in previous seasons. And time will tell, we're just now getting into what theoretically might be RSV season for 2023 so it'll be interesting to watch how that goes.

Speaker 1  38:44
I think it happened a lot earlier, too, if you look at some of that tracking data and where it peaks, it was a bit earlier than we've seen in

Dr. Sean Kane  38:52
years past. It was so again, emphasizing how this may not be as predictable as we think, in terms of when that peak really happens. So to kind of wrap up today's episode, you know, one key concept is just what is RSV? So RSV is a contagious respiratory virus. In most patients, it's mild and self limiting, but there is a small portion of patients that will have severe disease, especially younger kids or older adults, with risk factors it can lead to hospitalization and death. So this can be a very serious infection for some patients.

Speaker 1  39:24
We also talked about how the FDA recently approved two new vaccines for RSV, so we saw Abrysvo from Pfizer and Arexvy from GSK. That initial approval was for adults six years of age and older, and that's what the ACIP grasped onto as well in terms of their recommendations, and then we also saw Abrysvo was FDA approved for pregnant women in that 32 to 36 week time frame pregnancy to help protect the newborn infant from severe RSV infections.

Dr. Khyati Patel  39:55
When we are looking at our older patient population, both vaccine. Incidents met efficacy criteria. But as we discussed, the incidence of RSV infection, even though the study sizes were really large, were relatively low, so that makes our number needed to treat pretty high. Keep in mind, these studies were done at the time of low RSV prevalence, and you know, most likely the NNT would be favorable when there is more cases of RSV going out, such as the outbreaks.

Dr. Sean Kane  40:30
Then finally, unlike Abrysvo though, the GSK version, Arexvy contains an adjuvant, actually two different adjuvants, and the intent of that is to improve the immune response. And although we can't directly compare the side effect profile orexp probably does appear to have more systemic adverse effects like fever, myalgia, headache and fatigue. So that may be something to think about in patients that maybe don't respond well to those kinds of side effects when they receive other vaccinations or a good opportunity for patient counseling when it comes to these vaccinations.

Speaker 1  41:06
And as the title of our podcast would entail, we have a monoclonal antibody newly available as well, nirsevimab, and that's going to be for our infants. Give it a two different points, all of our infants less than eight months of age as they enter their first RSV season, would receive that particular monoclonal antibody, and then, as someone eight to 19 months who is at high risk and entering the second season may also receive that monoclonal antibody,

Dr. Sean Kane  41:37
perfect Well doctor. Angelo, thank you so much for your time and expertise today, as always, we really appreciate it.

Speaker 1  41:43
It was great to be here. Thank you for the invitation

Dr. Sean Kane  41:46
and for the listeners. We love the five star reviews on iTunes, so keep those coming. We also have a mailing list so you can receive an email when new episodes come out, and we're on Twitter at HelixTalk, so feel free to reach out to us there. So with that, I'm Dr. Kane,

Dr. Khyati Patel  42:00
I'm Dr. Patel. Thank you so much again. Dr. Angelo and to our audience, study hard.

Narrator - Dr. Abel  42:06
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Narrator - ?  42:17
suggest an episode or contact us. We're online at HelixTalk.com. Thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.