Nina Cosdon

This article was originally published in 

The US Food and Drug Administration (FDA) has approved Abrysvo, a 

The approval will allow Pfizer to move forward with the vaccine for individuals aged 60 years and older to prevent lower respiratory tract disease caused by RSV.

) vaccine, is composed of 2 preF proteins specifically chosen to optimize protection against RSV A and B strains.

“A vaccine to help prevent RSV had been an elusive public health goal for more than half a century," said Annaliesa Anderson, PhD, senior vice president and chief scientific officer of vaccine research and development at Pfizer, in a statement. “Abrysvo will address a need to help protect older adults against the potentially serious consequences of RSV disease. We are extremely grateful to the clinical trial participants, study investigator teams and our dedicated Pfizer colleagues for their roles in making this vaccine available.”

In the more than 50 years of working to develop an RSV vaccine, Abrysvo is the world’s second-ever to be granted approval. Last month, 

GSK’s Arexvy (RSVPreF3 +AS01E) was approved

 to prevent lower respiratory tract disease (LRTD) caused by RSV in adults 60 years and older.

The FDA's decision to approve Abrysvo as well was based on data obtained from the pivotal Phase 3 clinical trial (NCT05035212) known as RENOIR (RSV vaccine Efficacy study iNOlder adults Immunized against RSV disease). RENOIR is a global, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, immunogenicity, and safety of a single dose of the vaccine in adults aged 60 and older.

Approximately 37,000 participants were enrolled in RENOIR, with half receiving RSVpreF 120 μg and the other half receiving placebo in a 1:1 ratio. RENOIR is an ongoing study, with efficacy data being collected during the second RSV season.

Edward E. Walsh, MD, Professor of Medicine at the University of Rochester Medical Center and principal investigator of the RENOIR trial, commented, "This 

 demonstrated the serious consequences and potential health risks this virus poses for older adults. Today’s FDA approval of Abrysvo recognizes significant scientific progress, and importantly helps provide older adults potential protection against RSV and an opportunity to improve community health by helping prevent the disease.”

RSV is a contagious virus that commonly causes respiratory illnesses worldwide. It primarily affects the lungs and breathing passages, often leading to severe illness or even death. In the US, RSV poses a considerable burden on older adults, with disease severity increasing with age and comorbidities such as chronic obstructive pulmonary disease, asthma, and congestive heart failure.

In most healthy individuals, RSV manifests with mild, cold-like symptoms. Most people recover within 2 weeks, often without knowing they had contracted RSV. Infants and young children, however, are also susceptible to the worst of RSV infection. Thus, Pfizer is also seeking approval to administer 

 to pregnant persons, with the goal of preventing medically attended lower respiratory tract disease (MA-LRTD) and severe MA-LRTD caused by RSV in infants from birth to 6 months of age.

 by the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), and a decision is expected by August 21, 2023.

Regarding the use of RSV vaccines in older adults, the US Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) is scheduled to meet on June 21, 2023, to discuss recommendations. Pending the outcome of this meeting, Pfizer expects Abrysvo to be available in the third quarter of 2023, just ahead of the anticipated RSV season this fall.

In addition to this recent approval, Pfizer reported positive top-line results earlier this month from a Phase 3 study that evaluated the safety and immunogenicity of Abrysvo coadministered with seasonal inactivated influenza vaccine (SIIV) in adults aged 65 and older.

Furthermore, Pfizer announced its plans to conduct multiple clinical trials evaluating RSVpreF in healthy children aged 2-5 years, children aged 5-18 years with comorbidities, adults aged 18-60 years with comorbidities, and adults aged 18 years and older who are immunocompromised and at high risk for adverse RSV outcomes.

Articles

The approval for Abrysvo represents the second RSV vaccine approved for adults aged 60 years and older in the last month.

FDA Approves RSV Vaccine for Older Adults

This article was originally published ContagionLive.

The US Food and Drug Administration (FDA) has approved Arexvy (RSVPreF3 +AS01E), an adjuvanted 

The vaccine, developed by GSK, was approved to prevent lower respiratory tract disease (LRTD) caused by RSV in adults 60 years and older, making it the first-ever RSV vaccine approved for older adults.

RSV is a common respiratory virus that typically causes mild, cold-like symptoms. While most people recover within 2 weeks, infants and older adults are susceptible to severe and even fatal infection. Older adults with comorbidities, including diabetes and chronic heart and lung disease, are at an increased risk of RSV hospitalization and death.

“In the United States today, there are about 177000 hospitalizations due to RSV, and about 14000 deaths due to RSV in older adults aged 65 years and above,” Temi Folaranmi, MD, VP, US Medical and Clinical Affairs, Vaccines at GSK, told 

. “The opportunity to have a vaccine that would address this burden of disease is a significant public achievement.”

The FDA approval comes after reviewing positive phase 3 data from the AReSVi-006 (Adult Respiratory Syncytial Virus) trial.

“Our primary endpoint in our study was to look at protection against lower respiratory tract disease caused by RSV, which gives us an excellent efficacy of about 82.6%,” said Folaranmi. “We also look at other endpoints such as acute respiratory illness, which gives us a very high efficacy as well.”

The secondary trial endpoint was to evaluate Arexvy in patients with comorbidities, in whom Folaranmi said there was a vaccine efficacy of 94.6%. Against severe disease, the efficacy was 94.1%.

“The RSV vaccine is made up of 2 components,” Folaranmi explained. “We have the preF fusion protein, which is combined together with a well-known adjuvant, the AS01 adjuvant.”

“The combination of these 2 components provides very strong efficacy that is able to address the natural decline that you see in an immune system due to aging.”

The FDA’s Vaccines and Related Biological Products Advisory Committee 

 in favor of the safety and efficacy of GSK’s investigational RSV vaccine.

“The opportunity to have a vaccine that can prevent this significant burden of disease is huge,” said Folaranmi. “Before now, there was no known intervention for addressing respiratory syncytial virus illness.”

Older adults with comorbidities, including diabetes and chronic heart and lung disease, are at an increased risk of RSV hospitalization and death.

FDA Approves Arexvy, the First  RSV Vaccine for Older Adults

There’s a different respiratory virus making headlines this season.

 is a common respiratory virus that typically causes mild, cold-like symptoms. While most people recover within 2 weeks, infants and older adults are susceptible to the worst of the infection.

The past couple of years, COVID-19-inspired preventative measures had the added benefit of reducing the incidence of other viruses like influenza and RSV. Now that practices like masking and social distancing are falling out of favor, we are seeing an increase in seasonal respiratory viruses.

RSV spiked early and violently this year, with infants under 6 months and adults over 65 years experiencing severe and fatal infection. “We’ve actually had summer outbreaks of RSV in the last couple of years, which is very, very unusual” said Tina Q. Tan, MD, a professor of pediatrics at Northwestern University’s Feinberg School of Medicine, medical director of the International Patient Services Program (IPS); co-director of the Pediatric Travel Medicine Clinic; and director of the International Adoptee Clinic at Ann & Robert H. Lurie Children’s Hospital of Chicago.

This year’s high rate of severe RSV infections is unprecedented, even in years before the public actively worked to lower disease transmission. The Centers for Disease Control and Prevention (CDC) 

 RSV hospitalizations for children 0-4 years of age peaked at 237.2 per 100,000 people, while hospitalizations in adults older than 65 years peaked at 17.6 per 100,000 people.

Overall hospitalizations this season peaked at 19.5 per 100000 people. For reference, the previous high was a peak of 8.8 overall hospitalizations per 100,000 people, recorded during the 2019-2020 RSV season.

“It’s just been massively out of control this year…People are acutely feeling it now due to the intensity of the peak,” said Iona M. Munjal, MD, director of clinical research and development at Pfizer.

Munjal explained that most children are exposed to RSV by the age of 5, and easily clear the virus. Now, as schools and daycares begin to open post-pandemic, large numbers of young children are experiencing severe RSV after being exposed to the virus for the first time.

RSV was first formally identified in the 1950s. Since then, Munjal said, there have not been effective solutions. “There is a single monoclonal that you give to infants that is very, very costly, and it requires a monthly injection, so it’s only given to high-risk infants.”

There is another extended duration monoclonal antibody completing phase 3 trials, which Tan called a “very promising development.” This monoclonal would be for healthy preterm and term infants, greater than 29 weeks gestation. If authorized, infants would receive a single dose of this monoclonal antibody prior to RSV season, and due to its extended duration, 1 dose would last the entire RSV season.

Of course, a high incidence rate of RSV does not mean other respiratory viruses have disappeared. Quite the opposite; fears of a confluence of RSV, influenza, and COVID-19, which some are calling a “tridemic,” are very real. “In addition to those 3 viruses,” said Tan, “there are other respiratory tract viruses that are also circulating that play into this mix.”

Unlike COVID-19 and flu, there is no approved vaccination to combat RSV. However, this could be about to change.

The COVID-19 pandemic demonstrated the rapidity with which a vaccine can be developed when there is a drastic unmet need. RSV has been circulating for decades longer than COVID-19, so why has it taken so long to get this close to the first authorized RSV vaccine?

Munjal says that the RSV virus is particularly elusive. “What's really interesting about RSV is that it comes in, it changes its shape, and then it attaches to the human host cell,” she explained. “This shape change was something we didn’t know at first.”

Tan reiterated the challenging structure of the RSV organism. She said there are a few RSV vaccines that have successfully completed phase 3 clinical trials and are going to be submitted to the US Food and Drug Administration (FDA) for licensure.

Pfizer’s bivalent RSV prefusion vaccine candidate, RSVpreF or PF-06928316, accounts for the virus’s shape change. “We target the prefusion form of the virus,” said Munjal. The vaccine candidate is administered to pregnant people to help protect their infants from RSV after birth.

After sharing positive phase 3 data from the RSVpreF investigational vaccine, 

 plans to submit a Biologics License Application (BLA) to the FDA by the end of 2022.

Munjal says the fact that we are on the precipice of the first approved RSV vaccine makes it easier to talk about this season’s high incidence. “I think that when you have solutions, people are more able to talk to the problem,” Munjal commented, “because otherwise, it's frustrating.”

Tan specifically noted that the Pfizer maternal vaccine is the most promising. “The pregnant woman gets a dose of this vaccine,” she said, “and data from the phase 3 trials show that it is 82% effective preventing RSV lower tract disease in infants during the first three months of life. So it is very, very promising.”

There are other RSV vaccines on the horizon, albeit not as far along as the Pfizer maternal vaccine. “There are some RSV vaccines that are still in very early clinical trials,” said Tan. “These are intranasal RSV, vaccines that will be used in children somewhere between 6 months and 24 months of age.”

When asked why Pfizer is focused on maternal vaccination, Munjal cited its safety and efficacy. “I'm a pediatrician; if I could prevent half of the babies coming into the hospital, I would,” said Munjal. “82% [efficacy] for me is a really, really amazing achievement for the vaccine. And we're very excited.”

Munjal also noted maternal vaccination ensures high levels of antibodies are passed to infants: “We found that in some cases, moms were passing more antibodies to the baby than they kept to themselves…So relatively, they're transferring a very, very high load of antibodies to the baby.”

Respiratory viruses can be especially dangerous for pregnant people and their infants. Unfortunately, there has been an uptick in vaccine misinformation during the COVID-19 pandemic that could impact vaccinations among the most vulnerable populations.

“I think one of the biggest misconceptions is…that that moms aren't into taking vaccines,” said Munjal. “We've shown that in countries in which vaccines can be widely available, the uptick in the pregnant population is really quite good.”

Munjal emphasized that although US is experiencing a high rate of RSV in infants, these infections can be even more fatal in other nations. Therefore, the Pfizer RSV vaccine trials included a number of other countries. “Outside of the US, we have 17 other countries…we thought it was equally important to gain data in those countries.”

As previously noted, older adults are also disproportionately likely to experience severe or fatal RSV disease progression. Munjal said that Pfizer plans to submit a Biologics License Application (BLA) for both maternal and older adult populations. “The same dose that we give to pregnant women, it showed efficacy this year in older adults.”

The most common symptoms of RSV are congestion or runny nose, coughing, loss of appetite, fever or chills, sneezing, sore throat, and wheezing. While these do overlap with COVID-19 and flu symptoms, sneezing and wheezing specifically are unique to RSV.

The best way to know if one is experiencing RSV, Tan says, is to get tested, especially if the infected person is a young child or older adult. “If you have someone presenting to you that is sick enough to seek medical care, you really need to test them to determine which one of these viruses, or 

 of these viruses.” Coinfection can occur, and knowing how to treat these patients can be lifesaving.

RSV is not new, but while in the past people experiencing the virus would settle for simply calling it “a cold,” Munjal says that the severity of the COVID-19 pandemic has heightened our attention to respiratory viruses.

“I think from a pediatric perspective, I'm always struck by how prevalent the virus is,” said Munjal, noting, “almost 100% of kids have this by age 2, so you don’t get away from RSV. It’s so prevalent and so contagious that almost everyone is exposed.”

Munjal also explained why RSV is so much more deadly for infants and young children. RSV causes a large volume of fluid to build up in the lungs. While this is only mildly dangerous for adults, who have a large breathing tube, “babies are breathing through a breathing tube that's the size of a straw, and it completely fills up with fluid, and you see them struggling to breathe,” said Munjal.

“Since the 1960s, you say, ‘Oh I know your baby has RSV, and there’s nothing I can do,’” explained Munjal. An RSV vaccine would certainly be beneficial on a global level, by significantly reducing the strain on hospital resources. But Munjal noted a vaccine is also about “That really, really impactful, patient-by-patient experience…That’s the joy in this vaccine, you can finally say, ‘I have something to offer.’”

Keep up with the latest developments in RSV, vaccines, and RSV vaccines on 

Why has this season brought an unprecedented number of severe RSV infections, and why is vaccine development taking so long?

The Race to the First RSV Vaccine: How Close Are We, and Why Has It Been so Difficult?

The US Food and Drug Administration’s (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted on September 22 to recommend a Biologics License Application (BLA) for RBX2660 (Rebyota) to treat recurrent 

The treatment, developed by Ferring Pharmaceuticals, is aimed at reducing recurrent CDI after antibiotic usage by being administered as a pre-packaged single-dose, consisting of 150 mL microbiota suspension from individual human stool donation.

Are the available data adequate to support the effectiveness of REBYOTA to reduce the recurrence of 

 infection (CDI) in adults 18 years of age and older following antibiotic treatment for recurrent CDI?

Are the available data adequate to support the safety of REBYOTA when administered to adults 18 years of age and older following antibiotic treatment for recurrent CDI?

VRBPAC voted 13 to 4 in favor of the first question, and 12 to 4 in favor of the second, with 1 abstention.

RBX2660 is a standardized, stabilized, investigational microbiota-based live biotherapeutic. It reduces the cycle of recurrent C diff infections by restoring the gut microbiome and inhibiting antibiotic-induced dysbiosis.

There are other treatments for patients with recurrent CDI, such as fecal microbiota transplantation (FMT). However, FMT is only recommended for patients with multiple recurrences who have also failed applicable antibiotic treatments. RBX2660 is intended to treat patients suffering from debilitating CDI, but who may not qualify for FMT.

CDI has a high rate of morbidity and mortality, in addition to draining health care resources. Approximately 500,000 Americans contract C diff each year, and 30,000 die from this highly resistant bacterium. This burden becomes greater and deadlier with each CDI recurrence.

The treatment was previously granted Fast Track, Orphan, and Breakthrough Therapy designations by the FDA. The treatment will be administered as a pre-packaged single-dose, consisting of 150 mL microbiota suspension from individual human stool donation.

, proton pump inhibitors, previous CDI, health care exposure, age above 65 years, and comorbid conditions such as malignancy, kidney disease, inflammatory bowel disease, and immunosuppression.

RBX2660 is a standardized, stabilized, investigational microbiota-based live biotherapeutic. 

Nina Cosdon

Articles

FDA Approves RSV Vaccine for Older Adults

FDA Approves Arexvy, the First RSV Vaccine for Older Adults

The Race to the First RSV Vaccine: How Close Are We, and Why Has It Been so Difficult?

FDA Committee Recommends Approval for Live Microbiota C Difficile Medication