The Food and Drug Administration’s independent advisors recommended on Tuesday what could become the world’s first RSV vaccine, a shot from Pfizer for adults aged 60 and older, despite safety concerns following two trial participants developing a rare neurological disorder.
A majority of the FDA committee members supported the vaccine, but they faced challenges with separate votes on whether the safety and efficacy data were adequate to justify the agency’s approval. The FDA is expected to make its decision in May.
Currently, no vaccine exists to protect older adults from respiratory syncytial virus (RSV), which kills thousands of seniors every year. Pfizer’s shot could be the first to receive FDA approval.
In the first vote on Tuesday, seven FDA committee members deemed the safety data adequate for approval, four said it was not, and one member abstained.
The vote came after concerns were raised at the FDA and among advisory committee members about two cases of Guillain-Barre syndrome in approximately 20,000 vaccine recipients. Guillain-Barre is a rare neurological disorder in which the body’s immune system mistakenly attacks the nerves.
Symptoms of Guillain-Barre can range from brief weakness to paralysis, but most patients, even those with severe cases, recover.
In the second vote, seven committee members said the vaccine’s effectiveness data was adequate, while four said it was not, and one member abstained.
The shot was about 86% effective at preventing lower respiratory tract illness with three or more symptoms and 66.7% effective against the same condition with two or more symptoms, according to an FDA review of Pfizer’s data. Symptoms included wheezing, shortness of breath, rapid and shallow breathing, and mucus production.
According to the Centers for Disease Control and Prevention (CDC), RSV causes 6,000 to 10,000 deaths and 60,000 to 160,000 hospitalizations per year in adults aged 65 and older. The risk of hospitalization increases with age, and adults aged 70 and older are more vulnerable.
Among adults of all ages hospitalized with RSV, 19% require intensive care, and 4% die, according to CDC data from three seasons. Mortality is highest among seniors.
Pfizer’s vaccine targets both strains of RSV, which circulate simultaneously during fall and winter. The shot is administered as a single 120-microgram dose.
The FDA considers the two Guillain-Barre cases during the trial as possibly linked to the vaccine, said Dr. Nadine Peart Akindele, an agency official. The FDA has asked Pfizer to develop a safety study to monitor Guillain-Barre risks after approval, which the company has agreed to do.
A 66-year-old man in the U.S. developed Guillain-Barre, and a woman of the same age in Japan was diagnosed with Miller Fisher syndrome, a variant of Guillain-Barre.
They developed symptoms seven and eight days after vaccination, respectively. The woman has since recovered, and the man’s symptoms were resolving as of the last update, according to the FDA.
However, Alejandra Gurtman, a Pfizer executive, maintained that the company did not identify any safety concerns during the trial and that the vaccine was well tolerated.
Gurtman pointed to other potential causes of the Guillain-Barre cases, noting that the man had suffered a heart attack and the woman had an upper respiratory tract infection. But Dr. Marie Griffin, an FDA advisory committee member, said the cases raise serious safety concerns.
“It seems to me that one case is a red flag. Two cases are very concerning, and it’s concerning to me that Pfizer doesn’t think that there are any safety concerns,” said Griffin, a professor of health policy at Vanderbilt University Medical Center.
Dr. Hana El Sahly, who chairs the FDA advisory committee, also said the Guillain-Barre cases raise a significant safety concern. El Sahly noted that the disease has an incidence of about 1 in 100,000 among people aged 60 and older, but in the trial, the rate appears to be 1 in 9,000.
“So this is major if we take it at this level,” El Sahly said, while acknowledging significant uncertainty about the actual rate of the disease among vaccine recipients. “But nonetheless, it’s significant in terms of incidence,” she said.
Dr. David Kaslow, a senior official in the FDA’s vaccine division, emphasized that safety monitoring will be “critically important” if Pfizer’s RSV vaccine is approved.
The FDA is currently reviewing Pfizer’s proposal to study the risk of Guillain-Barre syndrome among Medicare beneficiaries. The FDA has the authority to require such a study after approval if deemed necessary.
Dr. Jay Portnoy, an FDA committee member, concluded that the safety data was adequate because Guillain-Barre syndrome is rare, and other adverse events in the trial occurred at similar rates among those who received the vaccine and those who did not.
Adam Berger, an official at the National Institutes of Health, expressed concern about the Guillain-Barre cases but stated that a larger study population is needed to determine whether there is an actual link to the shot. The post-approval study planned by the FDA and Pfizer could help answer this question, he said.
“I felt that I could vote yes at this point, with a heavy lean towards the real requirements of that post-market surveillance study,” said Berger, who is also an FDA committee member.
Incomplete efficacy data
At the time of Tuesday’s meeting, there was insufficient data to evaluate the effectiveness of Pfizer’s vaccine against severe disease requiring hospitalization, oxygen support, or a mechanical ventilator, according to the FDA. Data was also not available on the duration of protection provided by the vaccine, the agency noted.
Pfizer also did not have data on the vaccine’s effectiveness for elderly individuals with weak immune systems or those in frail health, according to the FDA.
Griffin, from Vanderbilt University Medical Center, expressed concern that the vaccine was tested in a relatively healthy population with low hospitalization rates and lacked data on nursing home residents and people in frail health.
Akindele, the FDA official, said real-world evidence after a vaccine rollout could reveal how much protection it offers for those in fragile health. The data could then be used to determine if the FDA needs to make any adjustments to how the shot is used, she said.
Pfizer is conducting its clinical trial over two RSV seasons with more than 34,000 people enrolled. The available efficacy and safety data are from the first season.
When asked what would happen if the second season’s data is not as strong after an approval, Akindele said the FDA would reevaluate the shot and reconvene the committee to determine the next steps.
Pfizer estimates that if 50% of people aged 60 and older receive the shot, the vaccine could prevent more than 5,000 deaths, 68,000 hospitalizations, 51,000 emergency department visits, and more than 422,000 outpatient visits.
