Becker's Hospital Review E-Newsletter

CDC Advisory Panel Recommends Seniors 'may' Get RSV Vaccine

A panel of experts that advises the Centers for Disease Control and Prevention on vaccinations opted Wednesday not to recommend that all seniors get a vaccine to protect against RSV.

Instead, the Advisory Committee on Immunization Practices said that anyone 60 and older should be able to get one of the new vaccines — being brought to market by GSK and Pfizer — if they and their physicians think it would be worthwhile.

Earlier in the day the committee looked set to vote on a stronger recommendation, one that would have urged all people 65 and older to get vaccinated against respiratory syncytial virus. But that recommendation was watered down after a long discussion during which several members of the committee expressed serious concerns about the decisions they were being asked to make based on the data the companies had provided. 

In the end, the committee voted 9 – 5 to recommend that people 65 and older "may" get an RSV vaccine, based on shared decision-making, a term that typically means a discussion between patients and their doctors. With these vaccines, it could also mean a discussion between patients and their pharmacists, because the RSV vaccines will be covered by Medicare Part D and as such will be administered in pharmacies in most cases. (It is difficult for physicians to get compensated for administering vaccines covered by Medicare Part D.)

The committee voted 13 to zero, with one abstention, to recommend the same policy apply to people aged 60 to 64.

The recommendations now go to CDC Director Rochelle Walensky for her endorsement. Walensky is expected to sign off on the recommendations sometime late this week or early next. 

The recommendations will likely lead to a lower uptake of the new vaccines than the manufacturers might have expected had the ACIP voted to accept the stronger "should" recommendation. At a point this spring, a GSK executive projected that sales of the RSV vaccine could rival those of Shingrix, the company's very profitable shingles vaccine. Both vaccines were approved for use in people aged 60 and older by the Food and Drug Administration last month. But the ACIP's RSV adult vaccine working group has been indicating for some time that it did not see a cost-effectiveness argument for recommending that everyone between the ages of 60 and 64 get vaccinated against RSV.

GSK's vaccine showed an overall vaccine efficacy of 82.6% against RSV-triggered lower respiratory tract illness in the first year after vaccination and 77.3% mid-way through the second year after vaccination. Pfizer's vaccine showed an efficacy of nearly 89% against RSV lower respiratory tract infection involving at least three symptoms in the first year after vaccination, and 78.6% efficacy mid-way through a second RSV season.

Michael Melgar, a CDC epidemiologist who co-chairs ACIP's RSV adult vaccine work group cautioned against comparing the two vaccines because the design of the clinical trials differed and the two companies were not measuring the exact same results.

The fact that the vaccines seem to protect for at least two years was new information presented at Wednesday's meeting and was credited for a big jump in the estimated price of the GSK vaccine. Prior to this meeting, GSK had been talking about a per dose cost of around $148. On Wednesday, the committee learned during a presentation of an economic analysis conducted by the CDC and the University of Michigan that the GSK price estimate had jumped to $270.

Both companies resisted strong pressure from the committee to commit to a firm price, with ACIP members arguing they weren't able to assess the cost-effectiveness of the vaccines without that information. 

"None of us buy a car unless we know how much it costs," said Helen "Keipp" Talbot, a geriatric infectious diseases specialist from Vanderbilt University. She urged the manufacturers to disclose their prices before the committee held its late afternoon vote. Just before the vote, the manufacturers came back with numbers, but both named a range.

Leonard Friedland, GSK's vice president for scientific affairs and public health, said the company's vaccine, which will be sold under the name Arexvy, will be priced within a "narrowed range" of between $200 and $295. Friedland argued that the cost reflects the fact that the vaccine's coverage will last at least two years. A Pfizer executive told the committee the company is "in the middle of competitive price negotiations" and cannot give a firm cost figure for its vaccine. But she said the Pfizer vaccine, which will go by the brand name Abrysvo, would cost between $180 and $270.

It is expected both companies will provide vaccines to the market in time for the next RSV season, which is normally in the winter. Since the Covid-19 pandemic, however, RSV activity has begun in the late summer and early fall and it is unclear if and when the old pattern of activity will resume.

These are the first vaccines to protect against this virus, which is a significant cause of hospitalization among very young children and seniors. In older children and adults RSV infections typically manifest as colds.

While researchers who study RSV in adults have hailed the arrival of these vaccines, the experts on the ACIP have been frustrated by the data the companies presented. Among their concerns was the fact that the clinical trials GSK and Pfizer conducted enrolled few adults 80 and older — the age group at highest risk from RSV. People who are immunocompromised and those living in congregate living settings such as nursing homes are also at elevated risk but were not enrolled in the studies.

Talbot noted that the committee is being asked to infer that because the vaccines were efficacious in the trials — largely in people in their 60s — they will also protect people in these other more vulnerable groups. 

"Randomized controlled trials are needed to determine vaccine efficacy in these groups at highest risk for RSV-associated morbidity and mortality," she argued. "[But] if vaccination is recommended for these groups, clinical trials will no longer be feasible for ethical reasons and we will have missed the opportunity to obtain the best level of evidence." Once a medical intervention is shown to be effective and is recommended for a population, it is no longer ethical to test it in a placebo-controlled trial.

There were also concerns about the fact that three people in the clinical trials done to test these vaccines developed Guillain-Barré syndrome after being vaccinated, a normally temporary condition in which people experience progressive paralysis. 

Some vaccines are associated with a slightly elevated risk of GBS. Whether RSV vaccines are among them will not be clear until more people use them, but several members of the committee were clearly disconcerted by the possibility that there might be a link between these vaccines and GBS.

Committee members expressed worry about the fact that these vaccines will likely be given at the same time of the year as flu and Covid shots and it's not yet clear if giving the vaccines at the same time undermines the immune responses they generate. Studies of concomitant administration of Covid and RSV vaccines are still underway. A study that GSK conducted giving RSV vaccine at the same time as high-dose flu vaccine — a formulation recommended for older adults — showed the response generated against influenza as "non-inferior" to what was seen when flu vaccine was administered on its own, with the exception of the response to influenza A H3N2 viruses. Those viruses cause the worst flu illness in seniors and some members of the committee were concerned that giving these vaccines at the same time could hurt protection against influenza.

Given that both vaccines appear to offer protection over two RSV seasons, it remains to be seen how often older adults would need to be vaccinated against RSV. Likewise it is not clear whether people who are immunocompromised will be protected by these vaccines. Pfizer said it is currently conducting a study to see if one or two doses of vaccine would protect this population. 

This story has been updated.

CDC Advisors Offer Lukewarm Endorsement Of GSK, Pfizer RSV Vaccines. What To Know.

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A production line at a GSK research and development center in Belgium. Ksenia Kuleshova/Bloomberg

In a surprising decision that could undermine the blockbuster sales expectations for Pfizer and GSK 's new respiratory syncytial virus vaccines, the Centers for Disease Control and Prevention's influential vaccines advisory committee gave only a lukewarm endorsement of the shots late Wednesday.

In a series of votes, the Advisory Committee on Immunization Practices backed a policy saying that adults aged 60 and up "may receive" an RSV vaccine, if they and their physician agree it's right for them. The decision didn't distinguish between the GSK and Pfizer shots.

In a presentation earlier in the day on Wednesday, a committee working group had suggested that the advisors issue a stronger endorsement for adults aged 65 and up, saying that adults in that age group "are recommended" to get the vaccine. The working group had suggested the softer "may receive" endorsement only for adults aged 60 to 64.

The switch came after a lengthy discussion among committee members, in which some advisors aired worries about efficacy of the vaccines in adults over the age of 75, who were underrepresented in trials. Others raised safety concerns, and some complained that the manufacturers hadn't disclosed final prices for the vaccines.

The committee makes recommendations to the CDC's director, Dr. Rochelle Walensky, who will make a final determination. On Thursday morning, GSK 's (ticker: GSK) American depositary receipts were down 1.4%, while Pfizer (PFE) shares were down 0.5%.

The two vaccines, GSK's Arexvy and Pfizer's Abrysvo, are the first RSV vaccines to receive Food and Drug Administration approval. RSV is a common seasonal respiratory virus that can cause severe illness in older adults and infants.

A number of other companies are also developing RSV shots, including Moderna (MRNA) and Bavarian Nordic (BNRY). Sanofi (SNY) and AstraZeneca (AZN) are waiting on an FDA decision on Beyfortus, a monoclonal antibody administered to newborns to prevent RSV infection, after an FDA advisory committee said it had a favorable risk-benefit profile earlier this month.

Both GSK and Pfizer have set up their RSV vaccines as likely blockbusters. In a presentation late last year, Pfizer said that it expected annual revenue of "more than $2Bn" from its RSV vaccines for older adults and expectant mothers. GSK's CEO Emma Walmsley said in January that she saw "multi-billion pound Shingrix-like annual potential" in her company's RSV vaccine, referring to the company's blockbuster shingles vaccine, which sold $3.6 billion globally last year.

Pfizer's projections, as laid out in last year's presentation, were based on an assumed peak vaccine uptake of 50% to 60% among older adults in the U.S. Whether the shot can still hit those numbers with a less-enthusiastic endorsement from the CDC remains to be seen.

The CDC says that it gives the "may receive" recommendation, known as "shared clinical decision-making," when "individuals may benefit from vaccination, but broad vaccination of people in that group is unlikely to have population-level impacts."

Wall Street analysts seemed unconcerned. "We continue to view PFE's RSV vaccine as one of the most important near-term commercial launches," Goldman Sachs analyst Chris Shibutani wrote on Wednesday. He said he expects 2030 revenue of $2.3 billion for the older adult and the maternal RSV vaccine, which is not yet FDA approved.

GSK, in a statement late Wednesday, said that "shared clinical decision making empowers patients in consultation with their healthcare providers to determine whether RSV vaccination is appropriate for them."

Thursday morning, in a separate statement, Pfizer's chief medical officer for vaccines/antivirals and evidence generation, Luis Jodar, said that the company welcomed the committee's recommendations. "It underscores the important role ABRYSVO may have in helping to alleviate the significant burden of RSV in older adults," Jodar said.

In a presentation to the committee early on Wednesday, GSK said that a single dose of its vaccine remained effective after two RSV seasons, but that revaccinating with an additional dose after the first 12 months didn't increase the vaccine's efficacy. 

Corrections & Amplifications: The FDA is scheduled to issue its decision on approval of Sanofi and AstraZeneca 's Beyfortus by the third quarter of this year. An earlier version of this article incorrectly said that Beyfortus had already received FDA approval.

Write to Josh Nathan-Kazis at josh.Nathan-kazis@barrons.Com

Regular Vaccinations For Most MS Patients Recommended By Experts

People with multiple sclerosis (MS) should generally follow a regular vaccination schedule similar to their healthy peers, with certain adjustments made if they're on particular disease-modifying therapies (DMTs), according to a group of experts in Europe who devised a set of more than 50 evidence-based guidelines for the safe and effective use of vaccines in MS.

The efforts were spearheaded by the European Commission for Treatment Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN).

The guidelines were published in a consensus statement, titled "European Committee for Treatment and Research in Multiple Sclerosis and European Academy of Neurology Consensus on Vaccination in People with Multiple Sclerosis: Improving Immunization Strategies in the Era of Highly Active Immunotherapeutic Drugs."

It was published in the Multiple Sclerosis Journal as well as the European Journal of Neurology.

Consensus statement a 'landmark achievement' for MS community

"The publication of this consensus statement is a landmark achievement for the multiple sclerosis community," Mar Tintoré, MD, PhD, ECTRIMS president, said in an ECTRIMS press release.

The statement marks the first European consensus on vaccination in people with MS, the release stated.

"ECTRIMS is proud to present this evidence-based guidance, which will serve as a valuable resource for healthcare professionals, patients, and their families," Tintoré added. "We believe that by implementing these recommendations, we can optimize vaccination strategies, minimize risks, and ensure the best possible outcomes for individuals with MS."

An autoimmune disease, MS is characterized by the immune system's self-reactive attacks on myelin, the fatty substance that surrounds and protects nerve cells, leading to neuroinflammation and neurodegeneration.

To combat these attacks, new DMTs typically involve some type of immunosuppression. While proven highly effective at easing symptoms and improving prognosis, such treatments can also leave patients vulnerable to infections that the immune system would normally fight off.

"An important part of the infectious risks for [people with MS] receiving highly active immunotherapies can be mitigated through vaccination," the researchers wrote.

Still, a number of questions remain as to how vaccinations should be managed in this patient population, including when and whether to administer a vaccine, and which specific DMTs might influence how effective a vaccine is.

Moreover, "vaccine coverage rates have been reported to be lower than desired for MS populations," the researchers wrote.

Led by ECTRIMS and EAN, a multidisciplinary group of MS and vaccine experts, as well as a patient representative, has now convened to recommend the best practices for immunization in MS patients.

"The core spirit of a joint ECTRIMS-EAN consensus is to afford 'one voice' on behalf of all parties concerned," said Thomas Berger, MD, EAN's scientific committee chair.

We believe that by implementing these recommendations, we can optimize vaccination strategies, minimize risks, and ensure the best possible outcomes for individuals with MS.

Guidelines based on analysis of studies related to vaccinations

The expert committee addressed key questions covering topics such as vaccine safety and effectiveness, global vaccination strategy, and vaccination in specific subgroups of MS patients. The resulting guidelines were based on an evidence-based analysis of existing studies related to vaccinations in this patient population.

While the consensus guidelines were extensive — amounting to 53 recommendations — a few key points were emphasized.

Vaccines are not linked to an increased relapse or disability progression risk in MS patients, regardless of DMT use, and "the benefit of immunization greatly outweighs any potential risks," the experts wrote.

As such, the committee recommended that doctors should evaluate a patient's immunization status and come up with a plan that involves vaccinations as soon as possible after an MS diagnosis.

Generally, children, adults, pregnant women, and elderly adults with MS should follow a regular vaccine schedule similar to the general population, including yearly flu and pneumococcal vaccines. Vaccines should be avoided during an active disease relapse, the committee noted.

Certain vaccines might be indicated or contraindicated depending on a person's prescribed DMTs, as the production of antibodies in response to a vaccine — an indicator of its effectiveness — is lower with use of certain DMTs.

These include anti-CD20 therapies (e.G. Ocrevus, Briumvi, and Kesimpta), S1P modulators (e.G. Gilenya, Mayzent, Ponvory, and Zeposia), and possibly Lemtrada (alemtuzumab) or Mavenclad (cladribine).

Live-attenuated vaccines should generally be avoided with certain MS therapies

Moreover, while inactivated vaccines, or those containing viruses that are dead and cannot multiplicate or cause infection, can generally be used at any time in all patients, live-attenuated vaccines may have more limitations.

Such vaccines, which contain a weakened form of a virus that can still grow but doesn't cause illness, should be given at least a month before starting DMTs or after steroid treatment.

Live-attenuated vaccines should generally be avoided when using therapies including Aubagio (teriflunomide), Tysabri (natalizumab), Tecfidera (dimethyl fumarate), anti-CD20 therapies, and S1P modulators.

"As more evidence becomes available regarding the long-term impact on the risk of infections of the new highly effective drugs available for treatment in [people with MS], changes in vaccination recommendations might occur," the researchers wrote.

In particular, the COVID-19 pandemic and the rapid development of new types of vaccines has provided a large amount of data on this issue in a short amount of time.

"This information on the infection–vaccination–immunity triad will likely lead to more studies to update future guidelines," the team concluded.

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