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Transcription:

Sarah: Hello and welcome once more to another episode of Avalere Health Essential Voice. Our podcast show covers a wide range of healthcare topics, and today we’re continuing our series on Respiratory Syncytial Virus or RSV.

My name is Sarah Moselle and I sit in the policy practice here at Avalere. We’re switching things up today and I’m joined by my colleagues Haley Payne and former host of the podcast, Elif Alyanak. We return to our RSV series with another episode looking at the future of RSV prevention, specifically among immunocompromised individuals.

Individuals with chronic heart or lung disease with weakened immune systems due to other comorbid conditions are at higher risk for severe RSV infection similar to older adults and infants. 94% of adults hospitalized with RSV between 2014 and 2018 had underlying medical conditions, 46% percent of whom, pardon me, had between one to two underlying medical conditions, and 48% having three or more conditions.

These included cardiovascular and lung disease, but also kidney and liver disease, neurologic disease, and diabetes. The CDC suggests there’s an even greater risk among transplant recipients, particularly individuals with lung and stem cell transplants and individuals receiving chemotherapy.

In general, the immunocompromised population can be difficult to develop a recommendation for. Would you agree, Elif?

Elif: That’s absolutely right, Sarah. I think it’s important to remember that vaccine recommendations for immunocompromised individuals need to consider the potentially attenuated immune response that such individuals could have to vaccines.

And I think it’s important to note that there are a host of different reasons why a person could be immunocompromised, like you said. Other factors like the person, the maintenance medication that the individual may be on, including those that are used to treat their immunocompromising condition and the vaccine platform that’s under consideration or the technology that’s being used can also play a role.

Ultimately, diminished vaccine immunogenicity in these individuals then translates into higher rates of clinical significant illness after vaccination and an increased risk in hospitalization. So ultimately recommendations for immunocompromised individuals can’t really be, by definition, one size fits all.

And I think we saw this previously with COVID 19. After the first vaccines were authorized for use and recommended by the advisory committee on immunization practices or the ACIP, a decision was then made to recommend a third primary dose for immunocompromised individuals in addition to their booster doses.

Haley: Yeah, that’s absolutely true, Elif, and these issues really highlight why passive immunizations like monoclonal antibodies can complement vaccination for immunocompromised individuals in particular.

So, ACIP considers data like these and other evidence of diminished immune response to make vaccine recommendations for those with immunocompromising conditions and the recent update to its charter to include recommendations for preventive monoclonal antibodies, or MABs, demonstrates opportunities to adapt recommendations and ensure adequate protection against severe disease and hospitalization for these individuals.

And I also want to note that just like the general population, emerging viral variants and seasonal pathogen circulation can lead to immune evasion as we’ve seen over time with influenza and COVID 19.

And like these other viruses, RSV is seasonal and dominant strains can vary. So a variant that evades what may already be more limited immune protection puts these immunocompromised individuals at a higher risk for a severe breakthrough infection and potentially subsequent hospitalization.

Sarah: That’s a great point, Haley. So what do you think this means in terms of how a future RSV product would be covered? Are there certain considerations or barriers to patient access that are unique to individuals who may have underlying conditions or are immunocompromised?

Elif: That is a great question, Sarah. Most health insurance coverage types, with the limited exception of Affordable Care Act or ACA grandfathered plans, are required to cover all ACIP recommended vaccines without any patient cost sharing.

So this includes vaccines that receive what we call any flavor recommendation, both routine or shared clinical decision making recommendations. This would also include vaccines covered by Medicare Part D or vaccines administered to traditional Medicaid beneficiaries beginning January 1st and October 1st, 2023 respectively as a result of the recently passed Inflation Reduction Act or the IRA.

It’s important to mention as well that insurance coverage is broadly distributed and can be variable among immunocompromised adults. So a 2021 survey found that most immunocompromised adults had health insurance through Medicare, followed by employer sponsored insurance and Medicaid.

Conversely, individuals who do not have immunocompromising condition, among them more than half had employer sponsored coverage. Significantly more immunocompromised adults reported being dually eligible than those without immunocompromising conditions.

So that was about 24% compared to roughly 8. 6%. Overall, as long as a vaccine, I’m sorry, has a recommendation for use from the ACIP insured individuals in the recommended population will be able to receive it at no cost, which I think is really important here.

And even without insurance coverage, there are some, albeit limited, pathways to getting vaccinated.

Haley: That’s absolutely right. So federally, the Section 317 program funds state run vaccine distribution and administration to uninsured and some underinsured adults depending on the state of course.

These programs are often limited though. So the 317 program funds certain vaccines and state programs can vary widely in who is eligible to receive free vaccines and which providers are eligible to offer and administer them.

So they’re not a 100% guarantee, but overall with the IRA being law, everyone with insurance coverage will be able to get free vaccinations. And this is really notable for RSV in particular.

For example, let’s say for Medicare, RSV vaccines could be covered under Part D, which historically could be accompanied by patient cost sharing, but starting next year that won’t be the case.

Sarah: I see. So aside from coverage and payment considerations, is there extra attention that needs to be given when we’re discussing monoclonal antibody and vaccine use, particularly among the immunocompromised populations?

Haley, what are your thoughts?

Haley: Yeah, absolutely. Right now, as we’ve mentioned in previous episodes, prophylactic prevention of RSV is essentially non- existent for the general population. However, the one option that is currently approved for use and available is palivizumab, which is specifically indicated for use in immunocompromised children under two years old.

So for individuals older than two who have high risk conditions and are at increased risk for severe RSV disease, there are no options. But looking beyond prevention, even treatments are limited, and they’re limited to antiviral therapy and immunomodulation with immunoglobulins, corticosteroids, and again, palivizumab in some unique cases.

So this really continues to make immunocompromised individuals particularly vulnerable to severe RSV illness and hospitalization.

Sarah: So in preparation for future vaccine and preventive products that can be indicated and recommended for use, what do about general vaccination rates among those who are immunocompromised and what could those rates mean for future RSV preventives?

Elif: Yeah, I think that’s an important question here as well. And we know that generally vaccination rates definitely vary by the vaccine type. So a recent GAO report noted a wide variance in adult coverage across four routinely recommended adult vaccines.

So that included flu, pneumococcal, shingles, and tetanus. Overall from that report, we see that uptake of flu and shingles is significantly lower than uptake of pneumococcal and tetanus. And while the report doesn’t really discuss rates among compromise individuals specifically, it does note that rates are higher among those with insurance coverage and among those who have at least one regular healthcare provider.

So looking back to what I said earlier, immunocompromised individuals may be more likely to have health insurance coverage, and individuals with complex or high risk health conditions often require more frequent visits to healthcare providers.

Usually they’re specialists to create additional touchpoints and opportunities for vaccination. However, these additional touchpoints don’t always directly translate to higher vaccination rates. So for example, looking at some 2021 data from a subset of patients specifically with inflammatory bowel disease, or IBD.

Those individuals often receive immunosuppressive therapies. And that indicates that these individuals do not necessarily receive preventive services at the same rate as general medical patients. All this to say, there’s another survey, the National Health and Wellness Survey, with data assessing flu vaccination among high risk adults, and that showed from 2007 to 2011 vaccination coverage rates though variable were higher among higher risk groups than among those not considered high risk.

So across other vaccines like Hepatitis B and pneumococcal immunocompromised groups had the highest vaccination rate. So this could be potentially promising for uptake of future RSV preventives.

Haley: And Elif, if you raised a really good point about healthcare providers, so guidelines from the American College of Gastroenterology for example, note the importance of emphasizing primary care in the IBD patient population, to your example earlier, to improve utilization of preventive services since they often view their specialists, their gastroenterologists, as their primary care provider.

And we’ve had some really interesting discussions here at Avalere about how other healthcare providers like specialists and particularly pharmacists can improve vaccination rates among certain patient populations.

This is a good area to explore for immunocompromised individuals, because like you said, they have frequent touchpoints with clinicians other than general practitioners.

Sarah: That’s a great point. And you mentioned future RSV preventives. Can you both share a bit more about what exists and what we’re seeing on the horizon?

Elif: Certainly. I think it’s important to go back to what Haley mentioned earlier and talk about what exists right now. So there’s ribavirin, which is an antiviral treatment, and there are some notable limitations for its use.

So the oral formulation isn’t often used for RSV treatment and the aerosolized formulation is really only approved for children, and that kind of leaves a gap for treatment in adults. Limitations aside, there are case studies that have noted successful oral ribavirin RSV treatment in immunocompromised adult patients, so that suggests that there’s certainly some opportunity there.

We also mentioned immunoglobulins and they can also be used as a preventive option, though they are certainly most often used as a therapeutic. Several studies have found that IV or intravenous immunoglobulin resulted in really beneficial effects, and that included reduced hospitalization time and lessened symptom severity.

It’s anticipated that immunocompromised patients could really benefit more from this therapy than those without immunocompromising conditions. And as we know based on the ACIP charter language, the ACIP is really open to reviewing evidence on immunoglobulins and monoclonal antibodies in an effort to make evidence- based recommendations.

So there are quite a few preventive options in the pipeline too, including vaccines and monoclonal antibodies that I think Haley can cover.

Haley: Absolutely right. And so to summarize from previous episodes, there are several products in phase three clinical trials including maternal vaccines, vaccines for older adults, and pediatric monoclonal antibodies.

There are also several vaccines in phase two, and then just a really robust preclinical and phase one pipeline to follow up on that. So all of these products could potentially receive indications and recommendations for use in immunocompromised populations.

So really I think it’s safe to say that pending study results and potential licensure, we can expect just an arsenal of RSV prevention options to both benefit the general population and to ensure immunocompromised individuals are adequately protected.

Sarah: I agree. Vaccination is a tool in disease prevention and overall public health is critical and equally important among individuals who may or may not have existing comorbid conditions. I want to thank Elif and Haley for joining me today, and thank you all for tuning in to Avalere Health Essential Voice.

If you’ve enjoyed this series, please reach out and let us know. And if you’d like to learn more, please visit us at our website at www. avalere. com.

Elif: Thanks, Sarah. Thanks Haley.

Haley: Thank you.