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FDA Approves First RSV Vaccine, But Some Experts Say Weak Safety, Efficacy Data Suggest Benefits Don’t Outweigh Risks

By Michael Nevradakis, Ph.D. | The Defender | May 4, 2023

Describing it as a “long-sought scientific achievement,” the U.S. Food and Drug Administration (FDA) on Wednesday approved Arexvy, the first vaccine for respiratory syncytial virus (RSV).

GlaxoSmithKline Biologicals (GSK) developed Arexvy under the FDA’s Priority Review designation. The FDA approved it for people ages 60 and older.

According to CNBC, the U.S. “suffered an unusually severe RSV season” this past winter. The New York Times reported on a “tripledemic” involving RSV, flu and COVID-19, “that swamped children’s hospitals and some I.C.U. wards.”

One U.S. county — Orange County, California — declared a local health emergency and issued a proclamation of local emergency in November 2022, citing rising RSV cases among children in the region.

GSK described results from clinical trials for Arexvy as “positive,” and the company said the U.S. launch of the vaccine is planned before the 2023-24 RSV season.

Other RSV vaccines, including one produced by Pfizer, are in the pipeline and expectations are that the FDA will approve them.

During clinical trials for both the GSK and Pfizer vaccines, several participants were diagnosed with rare conditions such as Guillain-Barré syndrome (GBS) and acute disseminated encephalomyelitis (ADEM). One of the individuals who developed ADEM later died, according to the FDA.

Aside from concerns over potential serious adverse events related to RSV vaccines, some experts have questioned the need for such a vaccine in the first place.

According to the journal Science, “RSV is a common respiratory infection” with symptoms “similar to a cold,” adding that “The majority of individuals recover within a few days from an uncomplicated RSV infection, although occasionally the virus can cause lower respiratory infections requiring medical attention.”

Dr. Peter McCullough, a cardiologist, told The Defender:

“Respiratory syncytial virus is a negligible threat to even the most frail elderly adults. The effort of widespread vaccination is simply not worth it. Even rare side effects will outweigh any theoretical benefit.”

And in a November 2022 episode of “RFK Jr. The Defender” podcast, several medical and public health experts expressed concerns about RSV vaccines.

“We have to stop these shots,” said Dr. Meryl Nass, an internist and biological warfare epidemiologist. “It’s just extraordinary that we’re still vaccinating people … we have a lot of work to do.”

Robert F. Kennedy Jr., then-chairman and chief litigation counsel for Children’s Health Defense (now chairman on leave), described RSV as “a vehicle for re-implementing the COVID-19 playbook all over the country and responding with vaccines.”

And according to the National Vaccine Information Center (NVIC), “Cost analysis data presented to the ACIP [Advisory Committee on Immunization Practices] did not show the RSV vaccines to be cost-effective at reducing the burden of costs associated with RSV illness.”

Nevertheless, more RSV vaccines are expected to receive FDA approval this year — including a Pfizer RSV vaccine for pregnant women that led to a high incidence of adverse events for both the women and their infants during clinical trials, as well as several deaths and stillbirths.

Arexvy approval ushers in new ‘highly competitive and lucrative vaccine market’

The RSV vaccine market is estimated to be worth up to $10 billion by 2030.

According to Endpoints News, the FDA’s approval of Arexvy ends “half a century of failed efforts against the elusive, shape-shifting virus” and “officially start[s] what analysts expect will be a highly competitive and lucrative new vaccine market.”

In getting Arexvy approved, “GSK beat a crowded field of competitors to cross the finish line first.”

Arexvy “showed strong efficacy in stopping lower-respiratory tract infections as well as more severe disease” and will be administered as a single dose, according to Endpoints News.

STAT reported that a “vaccine that was developed by Pfizer and aimed at the same demographic [adults 60 and over] is expected to be approved by the end of the month,” while other RSV vaccines and therapeutics, including some intended for children and pregnant women, are in the pipeline and also are close to receiving FDA approval.

The FDA’s approval of Arexvy came after an FDA advisory panel reviewed data from GSK’s and Pfizer’s clinical trials on March 1. The panel unanimously agreed that GSK’s vaccine is effective and, in a 10-2 vote, deemed it “safe,” according to The Washington Post.

The same panel also approved Pfizer’s candidate vaccine, Abrysvo, but with a 7-4 vote.

On June 21 or 22, ACIP, which advises the Centers for Disease Control and Prevention (CDC), will convene to “make recommendations on the appropriate use of the vaccine in the U.S.,” according to GSK’s announcement. The ACIP must recommend the vaccines before they are marketed.

According to STAT, there is a likelihood that ACIP may not approve Arexvy for its intended age group, stating:

“Though Arexvy’s approval is for adults 60 and older, it remains to be seen if the CDC will recommend it for that entire group.

“At an advisory committee meeting in February, members of a work group studying the adult vaccines that will soon come before ACIP indicated that at present, they don’t believe the vaccine would be cost-effective in people aged 60 to 64 and they would not recommend to the wider committee that it include people 60 to 64 in its recommendation for the use of the vaccine. (The group held the same position for the Pfizer RSV vaccine.)”

In April, the European Medicines Agency (EMA) issued its own recommendation for Arexvy, for adults 60 and over, according to the Times. However, a final EMA regulatory decision is anticipated later this year. GSK is also awaiting licensure for Arexvy in Australia, China, Japan and other countries, STAT reported.

In an earnings presentation April 26, GSK said it has “millions of doses” of Arexvy “ready to be shipped.”

According to CNN:

“GSK’s RSV vaccine works by using a small piece of the virus: a protein that sticks out on its surface called the fusion, or F, protein, which helps the virus glom onto and infect cells in the body’s upper airways. The protein pieces in the vaccine are made in a lab, using cells specially programmed to manufacture them.”

CNN noted that the vaccine “builds on a pivotal discovery made a decade ago” by National Institutes of Health researchers, “including some of the same scientists who helped make the COVID-19 vaccines.” Specifically, the researchers figured out how to freeze the otherwise “wiggly” F protein, “in the shape it takes before it fuses onto a cell.”

STAT, quoting Phil Dormitzer, GSK senior vice president and global head of vaccines research and development, reported that although Arexvy “contains only one of the two RSV subtypes, RSV A,” studies showed that it is “virtually equally protective against both RSV A and RSV B” as the F protein on both subtypes is similar.

Dormitzer acknowledged natural immunity, telling STAT, “because older adults have all had RSV probably multiple times by the time they get [the vaccine], they’re primed against both A and B. So you’re able to get very solid boosting against both subtypes with a single adjuvanted F antigen.”

According to GSK, the Arexvy vaccine does not use mRNA technology, but “contains a recombinant subunit prefusion RSV F glycoprotein antigen (RSVPreF3) combined with GSK’s proprietary AS01E adjuvant.”

GSK, FDA claim Arexvy clinical trial data show vaccine is ‘safe and effective’ but annual shot may be needed

The FDA announcement stated:

“The safety and effectiveness of Arexvy is based on the FDA’s analysis of data from an ongoing, randomized, placebo-controlled clinical study conducted in the U.S. and internationally in individuals 60 years of age and older.”

According to the FDA, “approximately 12,500 participants … received Arexvy and 12,500 participants … received a placebo. Among the participants who have received Arexvy and the participants who have received a placebo, the vaccine significantly reduced the risk of developing RSV-associated LRTD [lower respiratory tract disease] by 82.6% and reduced the risk of developing severe RSV-associated LRTD by 94.1%.”

LRTD was “defined as two or more symptoms including shortness of breath, wheezing, cough, increased mucus production, crackles, low oxygen saturation, or need for oxygen supplementation,” according to CNBC, while according to CNN, “People were considered to have severe disease if they needed supplemental oxygen or needed mechanical help to breathe, like a ventilator.”

According to the FDA, half of the 25,000 participants received Arexvy, while the other half received a placebo.

The results of GSK’s clinical trials for Arexvy were published in the New England Journal of Medicine on Feb. 16.

FDA and GSK officials provided glowing reviews of the new vaccine. Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, said in a statement:

“Older adults, in particular those with underlying health conditions, such as heart or lung disease or weakened immune systems, are at high risk for severe disease caused by RSV.

“Today’s approval of the first RSV vaccine is an important public health achievement to prevent a disease which can be life-threatening and reflects the FDA’s continued commitment to facilitating the development of safe and effective vaccines for use in the United States.”

Tony Wood, GSK’s chief scientific officer, described Arexvy’s approval as “a turning point in our effort to reduce the significant burden of RSV,” adding that “Our focus now is to ensure eligible older adults in the U.S. can access the vaccine as quickly as possible and to progress regulatory review in other countries.”

In turn, Dormitzer said, “There’s just the broad excitement of finally, after all these years, having good options emerging for RSV,” describing this as a “triumph of the basic science.”

While GSK is first out of the gate in the RSV vaccine race with Arexvy, Pfizer’s candidate vaccine has also completed clinical trials, which found it to be “nearly 67 percent effective in preventing R.S.V. – related illness,” according to the Times.

The FDA and GSK announcements did not mention the vaccines’ waning effectiveness. An analysis by the NVIC found that the effectiveness of the GSK vaccine peaked after two months and offered no protection after one year. This may result in recommendations for adults to receive annual doses of the vaccine.

Trial participant died from a rare inflammatory condition, others developed GBS

Despite positive comments from FDA and GSK officials, clinical trial data for Arexvy revealed instances of GBS and other rare conditions.

In its announcement Wednesday, GSK claimed:

“The vaccine was generally well tolerated with an acceptable safety profile. The most frequently observed solicited adverse events were injection site pain, fatigue, myalgia, headache, and arthralgia. These were generally mild to moderate and transient.”

The announcement did not mention GBS.

According to the FDA announcement Wednesday:

“The most commonly reported side effects by individuals who received Arexvy were injection site pain, fatigue, muscle pain, headache and joint stiffness/pain.

“Among all clinical trial participants, atrial fibrillation within 30 days of vaccination was reported in 10 participants who received Arexvy and 4 participants who received placebo.”

However, the FDA noted that in two other Arexvy studies involving approximately 2,500 participants 60 and over, “two participants developed acute disseminated encephalomyelitis (ADEM), a rare type of inflammation that affects the brain and spinal cord, seven and 22 days, respectively, after receiving Arexvy and the influenza vaccine.”

“One of the participants who developed ADEM died,” according to the FDA.

In another Arexvy study conducted by GSK, “one participant developed Guillain-Barré syndrome (a rare disorder in which the body’s immune system damages nerve cells, causing muscle weakness and sometimes paralysis) nine days after receiving Arexvy,” the FDA stated.

According to an FDA briefing document cited by CNBC:

“A 78-year-old woman in Japan was diagnosed with Guillain-Barré syndrome nine days after receiving GSK’s vaccine … She was hospitalized for six months before being released.”

CNBC reported that GSK claimed in February “There is insufficient evidence to confirm the woman got Guillain-Barre as a result of GSK’s shot.” However, the FDA “considers the case to be related to GSK’s vaccine.”

According to the FDA’s announcement:

“The FDA is requiring the company to conduct a postmarketing study to assess the signals of serious risks for Guillain-Barré syndrome and ADEM. In addition, although not an FDA requirement, the company has committed to assess atrial fibrillation in the postmarketing study.”

According to the Times, “Once the shots become available to the public, the agency said it would require GSK to monitor the incidence of Guillain-Barré and another rare condition that was possibly related to the shot.”

The FDA similarly flagged GSK “as a potential safety issue with Pfizer’s RSV vaccine for older adults,” CNBC reported after two clinical trial participants developed GBS. According to the Post, both participants — one man and one woman — were 66 years old.

CNBC in February reported that Pfizer “will conduct a safety study to further address Guillain-Barré syndrome if the FDA approves its vaccine.”

GSK’s chief commercial officer, Luke Miels, said the vaccine would cost upwards of $120 a dose, according to the Post, which also reported that private insurers may cover “many costs” associated with the vaccine, while Medicare patients with Part D coverage “won’t pay anything out of pocket” for the vaccine.

“Shares of GSK rose nearly 2% Wednesday following the approval,” CNBC reported.

GSK is also pressing forward with “A clinical trial that aims to expand the population who may benefit from RSV vaccination into adults aged 50-59, including participants with underlying comorbidities,” according to the company’s Wednesday announcement, with results “expected in 2023.”

Is there a need for an RSV vaccine?

According to the FDA:

“RSV is a highly contagious virus that causes infections of the lungs and breathing passages in individuals of all age groups. RSV circulation is seasonal, typically starting during the fall and peaking in the winter.

“In older adults, RSV is a common cause of lower respiratory tract disease (LRTD), which affects the lungs and can cause life-threatening pneumonia and bronchiolitis (swelling of the small airway passages in the lungs).”

The FDA cited CDC figures claiming each year in the U.S., RSV leads to approximately 60,000-120,000 hospitalizations and 6,000-10,000 deaths among adults 65 years of age and older.”

STAT reported that “RSV season has been unpredictable in the wake of the COVID-19 pandemic, though some experts believe RSV activity is moving back toward the seasonality seen in the pre-COVID days,” noting that “there was little transmission in 2020, when people were wearing masks and social distancing.”

But RSV “returned abnormally early in 2021,” STAT reported, but without an explanation for why this occurred, despite widespread masking and social distancing that year, too.

In the U.S., pediatric deaths from RSV are not common but the infection is the No. 1 cause of hospitalizations for children under the age of 1, STAT reported. Globally, however, it is the second leading cause of death in children under 1, after malaria.

According to STAT, “All but the youngest of children have had RSV multiple times, but few of us would know with any certainty that this bad cold was caused by that bad virus.”

Nevertheless, Pfizer is proceeding with the development of an RSV for infants as young as 6 months — “the age group at highest risk of being hospitalized with RSV,” STAT reported, noting that the vaccine for this age group is expected to gain FDA approval later this year and will be administered to pregnant women “to generate antibodies that protect both the pregnant person and their newborn.”

Data reported by Pfizer to the CDC indicated that 14% of pregnant women who participated in Pfizer’s trial sustained an adverse event, with 4.2% sustaining a “serious” adverse event, 1.7% experiencing a “severe” adverse event and 0.5% suffering a “life-threatening” adverse event.

Similarly, the same data showed that 37.1% of infants whose mothers received the experimental Pfizer vaccine experienced adverse events within one month of birth — with 15.5% classified as “serious,” 4.5% as “severe” and 1% as “life-threatening,” while efficacy waned within months of vaccination.

According to the NVIC, “The RSV clinical trial data also included the death of one pregnant woman, 18 still births (10 in vaccinated pregnant women and 8 in unvaccinated pregnant women), and 17 infant deaths (five from the vaccinated pregnancy group and 12 in unvaccinated pregnancy group).”

In its report to the CDC, Pfizer claimed the deaths were unrelated to the vaccine.

The FDA’s Vaccines and Related Biological Products Advisory Committee will meet virtually on May 18 to discuss approval of this vaccine. The meeting is open to the public, and a public comment period is open until May 17. A final FDA decision is expected in August.

According to the Times, “Moderna is also developing an RSV vaccine for adults 60 and over, with authorization expected in the first half of this year. The Times referenced clinical trial data released by Moderna claiming 82% efficacy, with “no safety concerns identified.”

Bavarian Nordic, known for its development of a vaccine in response to last year’s monkeypox outbreak, is also developing an RSV vaccine for adults 60 and over,” expecting to release Phase 3 clinical trial data by midyear, according to the Post and CNN.

AstraZeneca and Sanofi also are seeking FDA approval, but for nirsevimab, a monoclonal antibody treatment for RSV that would be administered to infants and toddlers up to age 2, according to the Times, which referenced clinical trial results claiming a reduction of illness of up to 75%.

According to the Post, nirsevimab “is already approved in Europe, the United Kingdom and Canada.”

However, the NVIC reported that the effectiveness of nirsevimab “is not known beyond 150 days” and it is unclear if the drug prevents ICU stays or deaths. It is being reviewed by ACIP, which according to the NVIC, is “a federal advisory committee charged with making vaccine use recommendations.”

“It is unclear why the ACIP … has chosen to go beyond its charge of making vaccine use recommendations,” NVIC states.

Safety concerns related to RSV vaccines nevertheless linger. According to CNN, an RSV vaccine developed in the 1960s for children initially delivered promising results during trials in children and animals.

However, once administered to children in the general population, “many of the children who were vaccinated required hospitalization and got more severe RSV disease than what would have normally occurred” — and two of the initial trial participants died.

Michael Nevradakis, Ph.D., based in Athens, Greece, is a senior reporter for The Defender and part of the rotation of hosts for CHD.TV’s “Good Morning CHD.”

This article was originally published by The Defender — Children’s Health Defense’s News & Views Website under Creative Commons license CC BY-NC-ND 4.0. Please consider subscribing to The Defender or donating to Children’s Health Defense.

May 4, 2023 - Posted by | Science and Pseudo-Science | , , ,

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