Wed. Jun 7th, 2023

The world has waited decades for vaccines to protect older adults against RSV. One, made by GSK, was approved by the Food and Drug Administration earlier this month. A second, made by Pfizer, is expected to follow by the end of May. Both will likely be in use this fall, in time to protect seniors going into the next RSV season.

So it’s tempting to think the fight against respiratory syncytial virus in older adults is about to kick into high gear, that as early as next winter the United States might start to see a turning of the tide in terms of the number of seniors who develop severe disease from a bout of RSV.

Maybe. Hopefully.

But there are a number of hurdles standing in the way of making the most of the new vaccines. Those hurdles — from a lack of awareness about RSV to safety concerns to issues around who will administer these vaccines — are lower than those that could inhibit use of emerging new products designed to protect young infants from RSV. Still, there are hindrances ahead and they aren’t insignificant.

For starters: There’s a lack of appreciation of the impact RSV infections have on older adults, experts who research this virus acknowledge.

“Certainly those of us who study it feel like there is an enormous need,” said Helen Chu, an associate professor of medicine at the University of Washington who specializes in adult infectious diseases. But Chu said there’s a disconnect between how people in her field feel about the threat of RSV, and how it is regarded by the target audience and their doctors. “There is not such a perceived sense of urgency and need in the older adult population.”

Ann Falsey, a professor of medicine at the University of Rochester, has spent decades mapping out the burden of RSV infection in this population. “RSV has a bit of an identity crisis,” she told STAT.

The virus is one of the more than 200 pathogens that trigger what we think of as the common cold. For most of a person’s life span, that’s the way RSV infection manifests — as a bad cold. But infections in the very young and in older adults are more severe and can be dangerous.

The detailed research that Falsey conducted suggested that in terms of its impact on older adults, RSV is a close second to influenza. “In our outpatient group, RSV was twice as common, but flu more frequently led to doctors visits and hospitalizations in healthy people,” she said.

The Centers for Disease Control and Prevention estimates that RSV infections in older adults in this country cause 6,000 to 10,000 deaths per year; 60,000 to 160,000 hospitalizations; and 900,000 to 1.4 million medical encounters. Others use higher figures.

“I think in places where we have looked systematically, it’s clear that the burden of hospitalization and ICU admission for RSV in older adults is pretty significant,” said Andrew Pavia, chief of the division of pediatric infectious diseases at the University of Utah. “[But] I think the average family doc and the average internist has very little appreciation of that.”

That lack of recognition could make it difficult to get older adults to agree to be vaccinated against RSV.

It has been enormously challenging to get this age group to agree to take additional doses of Covid vaccine — even though Covid has killed nearly 855,000 Americans ages 65 and older. Only 43% of people in this demographic have received one of the updated bivalent boosters.

Flu shot uptake in this age group is better. Depending on which CDC measurement tool you look at, somewhere between 53% and 71% of people 65 and older get a flu shot annually. But it has taken years of promoting and cajoling from public health departments and family doctors to reach those levels.

Yet GSK, whose vaccine for older adults was the first RSV vaccine ever licensed, feels it may have a blockbuster on its hands. Luke Miels, GSK’s chief commercial officer, told analysts in late April that demand for Arexvy, its RSV vaccine, could rival that of Shingrix, its highly successful shingles vaccine.

Pfizer also has a vaccine for this demographic barreling towards the market. (There are others further back in the pipeline as well.) Both vaccines will likely go before the CDC’s vaccine advisory committee at its next meeting in late June. If the Advisory Committee on Immunization Practices recommends these vaccines — and CDC Director Rochelle Walensky signs off on the recommendations — both will be available this fall.

Airfinity, a health intelligence and analytics firm, estimates 29 million doses of the vaccines could be administered in the U.S. in 2023, and sales of the RSV vaccines for older adults could reach $3.3 billion by 2024, based on a per-dose price of $115. Neither company has indicated what it plans to charge, but cost-effectiveness modeling the companies provided the ACIP’s RSV adult work group used $148 (GSK) and $200 (Pfizer) a dose as their price inputs.

Falsey, for one, thinks it will take time for demand for the vaccine to build. “I don’t think in the fall it’s going to have a huge uptake,” she said. “Because it’s not Covid, it’s not perceived as the emergency that that was. But I wouldn’t diminish it either.”

The first-year uptake figure — 29 million — that Airfinity used in its analysis would require nearly 52% of Americans over the age of 65 to get an RSV shot this year — a tall order. If ACIP follows the FDA’s lead and recommends the vaccines for people 60 and older, that projection would be an easier reach.

But here we hit hurdle No. 2: There’s a fair chance ACIP will not recommend the vaccines for adults 60 through 64.

At its meeting in February, the work group — comprising ACIP members, CDC staff, and outside RSV experts — indicated it would not recommend all adults 60 to 64 get an RSV vaccine. The work group made clear it didn’t think the vaccines would be cost-effective in that demographic. (See slides 72 and 75 in this presentation.)

Without a CDC recommendation, insurance companies would not be required to cover the cost of RSV shots for this age group. People who don’t feel RSV is a big deal are unlikely to pay out of pocket for a shot.

Falsey doesn’t think everyone over age 60 needs an RSV shot, but she worries an ACIP vote not to recommend the vaccines for people 60 to 64 could deter some people who would really benefit from getting one of the vaccines. “You’re out running marathons and biking 20 miles, and you’re not a smoker? You’ll probably do just fine with RSV,” she said in an interview. “But there’s a lot of people in that age group that have underlying heart and lung disease. They have COPD. They have heart failure. And those people are at markedly elevated risk for having a bad outcome.”

Another potential hurdle is a concern over safety. In clinical trials conducted to prove the GSK and Pfizer vaccines were safe and effective, three people out of the roughly 41,000 people who got one of the experimental vaccines developed Guillain-Barré syndrome or the related Miller Fisher syndrome.

GBS is a condition in which the immune system attacks nerves, leading to muscle weakness and in some cases paralysis. Most people recover, but some sustain permanent nerve damage. GBS can follow a viral or bacterial infection, like a stomach bug or a bout of influenza. But some vaccines, such as flu shots, have also been associated with a slightly elevated risk of developing GBS.

The background rate of GBS — the rate at which it occurs in the general population — is about 1 case per 100,000 people per year. Three cases in less than half that number — the people vaccinated in the adult RSV trials — gave pause to the members of ACIP’s adult RSV work group, Drexel University College of Medicine pediatrics professor Sarah Long said at the February meeting.

Barney Graham, a professor of medicine and microbiology, biochemistry, and immunology at Morehouse School of Medicine, cautioned about jumping to conclusions about these vaccines and GBS.

“If you’re enrolling compromised populations, older people, people with other complicating conditions, it’s not that surprising that you would see things like this come up during a trial,” said Graham, who with several colleagues solved the problem of how to make effective and safe RSV vaccines by stabilizing the F protein on the exterior of the virus’ surface.

“How that is going to play out, you can’t really study it until you get up to a million doses [of vaccine administered] or more,” he said.

(Graham stands to earn modest royalties from sales of RSV vaccines and he has worked with a number of companies on them. Chu, Falsey, and Pavia have also consulted with several of the companies pursuing RSV vaccines and antibody treatments.)

It is too soon to say if the RSV vaccines will be among those that increase the risk of GBS, or if they are, by how much. It’s also too soon to know whether an elevated risk of GBS would deter people from getting RSV shots.

GSK’s Shingrix, the blockbuster shingles vaccine, has been linked to a slightly higher risk of developing GBS. An FDA-ordered label warning notes that about three extra cases of GBS are typically seen for every million doses of Shingrix that are administered. That doesn’t appear to have dampened the appeal of the shingles vaccine; when it was first brought to market, higher-than-expected demand led to shortages. But people know about shingles and are motivated to avoid developing the painful condition.

These aren’t the only problems that may be standing in the way of broad use of the adult RSV vaccines.

It’s not yet clear if RSV vaccines will need to be given annually. But assuming they do — or even if they’re needed every second year — they are likely to be given in the early fall, at or around the same time as flu shots and Covid boosters are offered. In an ideal world, you’d give all three shots at the same time because the easier it is for people to get vaccinated, the more likely it is they will do so. Requiring people to make and keep multiple appointments increases the risk they won’t get all the recommended jabs.

But one can’t assume vaccines can be given concomitantly without having a negative impact on vaccine efficacy. A Pfizer-funded study that Falsey led found that giving RSV and flu shots at the same time led to a lower immune response to the flu vaccine — though the effect was more pronounced in younger adults, who got regular-dose flu shots, than in older adults, who received high-dose flu shots. Other research has shown when RSV vaccine is given at the same time as a tetanus, diphtheria, and pertussis shot, the response to the pertussis component is dampened. More study is needed, but it may turn out that giving RSV vaccine with other shots is ill-advised.

There are also questions about who will administer these vaccines and how they will get compensated for having done so. The complexities around this could limit the number of places where people who want an RSV vaccine can get one. It will also definitely limit who can get an RSV jab for free under Medicare.

RSV vaccines will be covered under Medicare Part D, a program mainly designed to compensate for prescription drugs and other services rendered by pharmacists.

Flu and Covid shots are covered under Medicare Part B; doctors bill Medicare for the cost of vaccine doses they have purchased and for actually administering the vaccination. But there isn’t a system in place that allows doctors to bill Medicare directly for vaccines covered under Part D.

There are some workarounds, said Juliette Cubanski, deputy director of the program on Medicare policy at KFF, formerly the Kaiser Family Foundation. Doctors can write a prescription for a vaccine and obtain it from a pharmacy. Using this approach, the pharmacy bills Medicare for the dose, and the doctor uses one of several online portals to seek compensation from the patient’s insurance company for giving the vaccination. “It is possible for physicians to be able to implement Part D vaccines and be reimbursed, but it is difficult,” Jason Goldman, an internal medical physician and the American College of Physicians’ ACIP representative, said at the committee’s February meeting.

Pharmacies could also administer RSV vaccines directly, though some states limit which vaccinations pharmacists can give and others require that pharmacists get a prescription from a doctor in order to vaccinate a patient.

“It is very complicated. And because it’s complicated, there is, I think, legitimate concern that these complications and administrative barriers will represent access barriers to beneficiaries getting the vaccine,” Cubanski said.

Adding to the complexity is the fact that Medicare Part D is a voluntary program. Older adults have to purchase Part D insurance — and not all do. Somewhere between 5 million and 6 million Medicare recipients do not have a Part D plan, Cubanski said. If those people want a vaccine that is covered by Part D, they have to pay the whole cost out of pocket.

“If the only way to get coverage for the RSV vaccine is through a Part D plan, and you don’t have Part D coverage, you essentially are not covered,” she said.

By Editor

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