RSV Unveiled: Breaking Down the New Vaccines on the Block

   

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TRANSCRIPT

Daniel Windoff:

RSV has been around and the thing with RSV is it takes up hospital beds in the ICU and it takes up ventilators. The people that end up in the ICU are either comorbid or elderly. So if they end up there, they’re going to take a breathing machine from somebody else. So if you can keep those out, that’s crucial.

Kyle Helton:

Ladies and gentlemen, welcome to the latest episode of the QPD Podcast. I’m your host, Kyle Helton, Western Regional Director here at Cambiar Investors. Today we have an incredible episode lined up for you. We’re delving into the rise of respiratory syncytial virus or RSV. What it is, who it affects, and the recent breakthroughs in vaccine treatments. We have two incredible guests joining us for the discussion. First up, we have Daniel Windoff, who is a Senior Analyst here at Cambiar, covering international healthcare. Daniel has over 14 years of industry experience and brings a global investment perspective on how advancements in RSV treatments are poised to impact the healthcare system and how GSK’s new RSV vaccine, Arexvy, is a critical component in fighting this battle. And also joining us today is Dr. Raymond Blum, a board-certified expert in internal medicine and infectious diseases. With over three decades of clinical experience. Dr. Blum is honored as a fellow of the Infectious Disease Society of America and will provide the practitioner’s perspective on the use and implications of vaccines for RSV. Thank you both for joining us today.

Dr. Raymond Blum:

Good morning. Thanks for having me here.

Daniel Windoff:

Thanks, Kyle. And good morning. Good to be here.

Kyle Helton:

To kick things off, Daniel, why do we think GSK is an interesting investment opportunity at the moment? And specifically, what makes RSV an interesting topic?

Daniel Windoff:

GSK is a leader in infectious diseases and vaccines. A couple of those leading assets within vaccines is its shingles vaccine, Shingrix, and its RSV vaccine, Arexvy. But GSK is more than that. It’s a leader in HIV and also has quite a few interesting assets across respiratory and oncology. In 2022, GSK became a pure-play pharma company following its spin of consumer healthcare business, Haleon. That led to a stronger balance sheet position and an opportunity to increase its focus on key assets and its pipeline. We view GSK as a quality company with an attractive return potential in what we believe is an improving operation. When we bought GSK, it was at a decade trough valuation. We took a very different stance on the outlook for GSK compared to what was priced in, in the marketplace.

Kyle Helton:

Interesting, a quality operator refocusing on core business. I can certainly see why that would be an attractive investment opportunity for us here at Cambiar. Maybe now would be a useful opportunity to share a little high level overview on RSV and who it impacts.

Daniel Windoff:

Yeah, sure. So RSV is particularly interesting at the moment since up until as late as last year, 2023, there were no available vaccines for the older adult population. And now we have two vaccines, both protein-based or traditional vaccines available. And this really is a game changer because the older adult population represents about 80 million people in the United States. And when it comes to hospitalization, the older adult population along with people with underlying disease are overrepresented among patients that end up in the hospital for severe RSV disease. Having a vaccine available is beneficial to vulnerable individuals, but also to the hospital system as a whole, especially in seasons where other viruses are prevalent.

Kyle Helton:

Wow, 80 million people who could be affected by this. I think this could be a good segue into a deeper dive into RSV. Dr. Blum, can you give a brief overview to our listeners of what RSV is, what it does to the body and why it’s important to prevent?

Dr. Raymond Blum:

Sure, Kyle, I’d be glad to. Before I go any further, let me just state that I have no financial disclosures in terms of any investments in any of these products that we may end up talking about. So RSV has come to light recently as we’ve learned more and more about it. It is a respiratory virus, which means it infects the respiratory tract, from your sinuses to throat to more importantly the lungs. We’ve known about it for many years. It’s come to light more recently as we’ve been able to test for it more and clearly has become a significant problem.

We now view it as probably the third-biggest respiratory illness to cause significant disease, both in terms of hospitalization and deaths. It traditionally been thought of as an infection that affected infants, especially those less than a year of age, as the most common respiratory infection leading to hospitalization and more severe disease, including something called bronchiolitis, which is inflammation of the airways that lead to asthma, for example. But now it’s become clearly more often recognized in adults, especially elderly adults, as a significant cause of hospitalization and death, ranked right behind influenza and now coronavirus, COVID-19.

Kyle Helton:

It’s interesting, and I’ve always thought of RSV as a seasonal issue similar to the flu and probably other respiratory issues that you’re mentioning. But as we’re having this discussion now entering spring, are we starting to see seasonality change?

Dr. Raymond Blum:

That’s a great question. Traditionally it has been a strictly seasonal virus, viewed as the ski season virus from late October into late April. The pandemic, due to the coronavirus, changed all our respiratory illnesses and we didn’t really have a big outbreak during the coronavirus, which shows the effectiveness of things like hand washing, masking to prevent all respiratory illnesses. However, as we quickly learned, as restrictions were eased, we’re back into a very significant seasonality to our RSV. This last season was classic in terms of late fall into just recently, it’s finally over.

Daniel Windoff:

And just as a follow up there, are you expecting that normal pattern to continue following the volatility that we saw in ’21, ’22? And maybe from a practitioner’s perspective, when should people consider getting a vaccine ahead of the RSV season?

Dr. Raymond Blum:

That’s a very good question. Obviously we can’t foresee into the future in terms of new pandemics that could alter our traditional seasonality to these viral infections. But assuming that doesn’t occur, I would expect the typical seasonality to occur. When we look at the efficacy, and we’ll talk a little bit this in terms of the new RSV, respiratory syncytial virus vaccines, it probably doesn’t matter when you get it. I think people get into their caregiver and if you have a chance to give the vaccine, it looks like they last a significant amount of time. Certainly if you have the option to do it right before the season, that may work. But if your only chance and their arm is in your office, do it then.

Daniel Windoff:

So when the Advisory Committee on Immunization Practice, or the ACIP, recommended both the Arexvy vaccine from GSK and the Abrysvo vaccine from Pfizer, but under shared clinical decision-making. What implication do you think that has had in practice?

Dr. Raymond Blum:

It brings up a lot of interesting things. This whole concept of shared clinical decision-making is relatively new. The example I like to use with shared clinical decision-making is that it really is a hedge and you want to look at the vaccine in terms of who you’re dealing with. For example, the human papillomavirus, HPV, we have a wonderful vaccine for it that can prevent cervical cancer. It’s a wonderful vaccine and we recommend it for all preteens. However, it is available for older adults.

But you can imagine if you’re in a monogamous relationship, the chances of getting HPV may be very small and in that situation we would say, “Hey, you should talk to your caregiver. Is it really worth getting the HPV vaccine?” I think the same is dropping out with the vaccines for respiratory syncytial virus in that they’re not vaccines that will offer the same benefit to every person. There are clearly groups that will definitely benefit from it, and that’s who we really need to target. Because there may be potential side effects that we don’t know about yet. They’re early in their development and some of these things may come to light later.

Kyle Helton:

So you mentioned a younger population, it being more recommended from the doctor with your HPV example, whereas the older population would engage more in shared clinical decision-making. As you think about RSV specifically as a vaccine, what group would benefit most from the vaccination in our population?

Dr. Raymond Blum:

We’re just getting the data, but it looks like the groups that are going to benefit the most are those that are over the age of 60, especially if they have underlying diseases that may allow them to do worse with respiratory syncytial virus.

Daniel Windoff:

It’s interesting with underlying disease. So I think AMA data points out that 94% of hospitalizations from RSV are patients with underlying disease. And a large portion of those, about half, have had three or more comorbidities. So on the comorbidity spectrum, within that group, who do you see having the most benefit from the RSV vaccine?

Dr. Raymond Blum:

Groups that are clearly highest risk are those with underlying lung disease, especially chronic obstructive lung disease, asthma. But also heart disease as well, cardiovascular disease and other chronic illnesses such as diabetes, chronic kidney disease, chronic liver disease. And those that are immune compromised, say they’ve had a stem cell transplant or a solid organ transplant, a kidney or liver transplant, are the ones most likely to benefit. An interesting thing that we’ve learned about as we’ve been able to test more for RSV, we like to compare it to influenza. Although there’s far more cases typically of influenza than RSV, if you do get admitted to the hospital with RSV, you’re more likely to end up in an intensive care unit than if you get admitted with influenza. So it tends to be a more severe illness when you do end up in the hospital with it. Not quite as bad as COVID-19, but certainly puts you at higher risk. So those groups are the ones we really have to think about trying to protect from RSV.

Daniel Windoff:

If we look at the two vaccines that are approved in older adults, what are the main differences that you observe between the two as we now have been on the market for a full RSV season?

Dr. Raymond Blum:

Well, in comparing the two vaccines, they are two different products. One is a bivalent vaccine that does not have an adjuvant. And there’s two forms of the RSV, A and B, that go back and forth during the seasonality. Is that an advantage? We don’t know. It looks like the other vaccine which contains an adjuvant is probably just as effective. So I’m not sure we can recommend one over the other based on what we know now until they were compared head to head. They both had phase three trials that went through different types of population, including Southern Hemisphere and Northern Hemisphere. Based on laboratory data, the adjuvant associated vaccine appears more immunogenic. Which is not surprising. So may offer, again, a key here is may offer some benefit to those that don’t respond well to vaccines such as the immune compromised or frail elderly, for example. We don’t know the answer to that yet.

Daniel Windoff:

Should we be concerned about more severe side effects?

Dr. Raymond Blum:

I think we should always be concerned about more severe side effects with vaccines to prevent disease, especially disease that’s going to be mild in the vast majority of people. I look back to 1976 when Gerald Ford recommended influenza vaccine for the swine flu and suddenly they picked up on a few cases of Guillain-Barré syndrome. However, in long-term follow-up, there seemed to be no association with the vaccine. But it was enough that they stopped vaccinating everybody. It’s not surprising that you give a vaccine which stimulates the immune system, especially elderly people to be more susceptible to side effects, that you could have these potential side effects, especially Guillain-Barré and other inflammatory nerve disease where the body attacks the nervous system as well as irritating the heart to cause some arrhythmias atrial fibrillation, for example. As far as we can tell, they’re extremely rare at this point, but it’s certainly something that we have to pay attention to. And as you start to expand vaccinating large populations, we need to maintain our antennas up and surveillance for these potentially more serious side effects.

Kyle Helton:

So we’ve learned a little bit more about RSV and its impacts on our population. We’ve learned about the cohorts that it most adversely affects, newborns, immunocompromised individuals, and the elderly. We understand that adoption is incredibly important to take stress off the healthcare system and all these various benefits. How, as a practitioner, do you think about increasing adoption in these populations specifically that would most benefit?

Dr. Raymond Blum:

Well, this has become a challenge and we are faced now with some vaccine hesitancy in this country and around the world, with good reason in terms of previous vaccines. If we look at the original RSV vaccine, which was taking the whole virus and using it as the vaccine, we saw a significant side effect in pediatric cases where they caused a worse disease and even deaths. This is twenty-some years ago before we truly understood how to create a safe, effective vaccine for RSV. So that pushed RSV vaccines out 20 years now before we finally have them. So I think with any new product or any new medication, this is where shared decision-making, I think, is important, where the caregiver can go over what’s available as we gain more data. Look, these vaccines becoming safer and safer. We realize that you’ve got diabetes, high blood pressure and heart disease, you’re somebody I would definitely would recommend that. So that’s the beauty of shared clinical decision-making, you get the patient involved through education and which is what we’re trying to do now with all the other vaccines.

Daniel Windoff:

And doctor, given the adverse reaction profile that we observe today, is there really an obvious reason why you wouldn’t, as a physician, not recommend getting the vaccine?

Dr. Raymond Blum:

Other than the initial reviewing that if they have an allergy. The absolute contraindication is if they have an allergy to any of the parts of the vaccine, which you have to review. No, I would present the data as clearly and simply as you can. “You’re somebody who has these diseases, it puts you at high risk. Were you get hospitalized, there’s a 15% to 30% chance you’ll end up in the intensive care unit. I can prevent that with this vaccine. These are the potential side effects. You may have a sore arm for a day, probably one in 100,000 risk of neurologic disease, but you would clearly be somebody that would benefit.” When I sit down with a patient often say, “If you were my X, brother, father, mother, I would recommend it. If you were my mother-in-law, I might not.”

Kyle Helton:

Thanks, doc. It’s been really interesting hearing a practitioner’s perspective of what’s going on in the world as it relates to RSV. I think this is a logical ending point for our conversation. I wanted to extend a huge thank you to our esteemed guests, both Dr. Raymond Blum and Daniel Windoff for sharing their insights today. To all of our listeners, thank you for tuning in. We hope you found today’s episode informative and thought-provoking. For more information and updates, please visit cambiar.com. And don’t forget to hit that subscribe button to stay updated on all future episodes of the QPD Podcast. Until next time, keep your investments smart, your curiosity alive, and your health of priority. I’m your host, Kyle Helton. Take care.