An independent panel of consultants from the Food and Drug Administration on Wednesday recommended GlaxoSmithKline’s The RSV vaccine is for adults aged 60 and over, although they noted potential safety issues due to nervous system disorders that may be associated with the vaccine.
Ten FDA advisors said the safety data for the GSK vaccine was adequate, while two said they were not. The committee unanimously stated that there is sufficient data on the effectiveness of the vaccine.
Panel reached similar conclusion in a narrow 7-4 vote on Tuesday on Pfizer’s application to purify its RSV vaccine. Although the consultants were wrong in recommending approval, they also raised concerns about a possible link to Guillain-Barré syndrome. One scientist abstained from this vote.
Respiratory syncytial virus kills thousands of elderly people every year. There is currently no approved RSV vaccine. The GSK injection is administered as a single dose of 120 mcg.
Both companies have applied to the FDA for approval of their RSV vaccine for adults aged 60 and over. The agency is expected to make a decision on the GSK vaccine by May 3, with a Pfizer response expected later that month. The respective GSK and Pfizer vaccines are set to be the world’s first approved vaccines to prevent the virus.
According to an FDA review of company data, the GSK vaccine was approximately 83% effective in preventing RSV-related lower respiratory disease during trials. The disease was defined as two more symptoms, including shortness of breath, wheezing, cough, increased mucus production, wheezing, low oxygen saturation, or need for oxygen support.
According to the FDA, GSK had no data on how long the protection from the vaccine lasts or how it works in people with weak immune systems.
“These data are robust and demonstrate potentially very high efficacy due to lower respiratory disease,” said the doctor. Amanda Cohn, committee member and chief medical officer of the National Center for Immunization and Respiratory Diseases.
But the consultants discussed at length the risks of rare nervous system diseases that may be associated with the vaccine. GSK said it is closely monitoring safety issues during testing and will continue to do so after eventual approval.
Dr. Hana El Sahli, chair of the committee, said more safety data was needed before approval. There was a case of Guillain-Barré disease in the trial and two people developed another rare nervous system disorder after being vaccinated against RSV and influenza, one of whom died. Dr. Marie Griffin, who also sits on the panel, agreed that more data is needed.
“I just don’t see why there is a rush to approve this vaccine now,” said Griffin, a physician at Vanderbilt University Medical Center.
A 78-year-old woman from Japan was diagnosed with Guillain-Barré syndrome nine days after receiving the GSK vaccine. Six months after the vaccination, she was discharged from the hospital. This woman was the only case of Guillain-Barré syndrome out of 15,000 people who received the vaccine.
GSK stated that there was insufficient evidence to support the diagnosis. The FDA believes the case is related to the vaccine.
Guillain-Barré syndrome is a rare neurological disorder with symptoms ranging from weakness to paralysis. Most people recover even after severe cases, according to the National Institutes of Health.
Two cases of Guillain-Barré syndrome were diagnosed during trials of the Pfizer vaccine against RSV. Griffin said the fact that such a rare disorder occurred in both companies’ studies is alarming.
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Griffin noted that Johnson & Johnson recorded one case of Guillain-Barré disease during trials of a Covid vaccine. The FDA eventually issued a warning for the J&J vaccine after it found an increased incidence rate. There were no cases of Guillain-Barré in large clinical trials of Covid vaccines by Pfizer and Moderna, she said.
“It’s not like you usually see one or two cases,” said Griffin, a member of the FDA committee that voted against the vaccine’s safety but in favor of its effectiveness.
Dr. Nicholas Gaigan, an FDA spokesperson, agreed that the Guillain-Barre cases in the GSK and Pfizer trials were worrying. GSK has agreed to expedite case reporting, Geagan said.
“Seeing these cases in the context of a clinical research program is worrying,” Gigan told the committee. “Therefore, we are discussing with the sponsor the further development of subsequent GBS safety assays.”
The FDA said in a white paper that the incidence of Guillain-Barré syndrome in the elderly is about 1 in 100 among people aged 60 and older. In the GSK trial, it was more like 1 in 15,000.
Dr. Ann Folsey, a professor of medicine at the University of Rochester, told the group that the frequency of Guillain-Barré systems increases with age, and there are other studies putting the rate between 8 and 15 per 100,000 people. Folsey participated in the GSK presentation to the committee.
Dr. Peggy Webster, head of vaccine safety at GSK, said rates of Guillain-Barré syndrome are higher in Japan, where the trial participant who developed the condition lives.
There were also two cases of another nervous system disorder, including one death, during the GSK trial, in which the RSV and influenza vaccines were given together. The patients developed what is called acute disseminated encephalomyelitis, a sudden onset of inflammation in the brain and spinal cord. These were the only cases among the 15,000 vaccine recipients.
The FDA has said that these cases may be related to either the GSK RSV vaccine or the flu shot that came with it.
A 71-year-old man developed a neurological disorder 22 days after vaccination against RSV and influenza. He was hospitalized after being found lying on the floor, shaking and trembling. A woman of the same age suffered headaches with double vision, forgetfulness, hand shaking, and uncoordinated movements. According to the FDA, she has shown improvement, but her symptoms have not completely disappeared at the time of the last update.
El Sahli, chairman of the FDA committee, said the incidence of this neurological disorder is typically 0.1 per 100,000 patients, mostly among children.
“Thus, two cases in older adults three to four weeks after vaccination are highly anomalous from a statistical standpoint,” said El Sahli, who voted against safety but voted for effectiveness.
Adam Berger, a spokesperson for the National Institutes of Health, said he believes cases of acute disseminated encephalomyelitis are more likely to be related to the simultaneous administration of RSV and flu shots, and not a problem with the GSK vaccine.
“I suggest relying heavily on post-marketing surveillance, and not only relying on, but making sure there is enforcement of the requirement to actually do it,” said Berger, an FDA committee member.
There have also been two cases of Bell’s palsy, which is weakness or paralysis on one side of the face. There was also a case of Graves’ disease, or an overproduction of thyroid hormones, a case of gout, and a case of a skin condition called psoriasis.
The FDA staff report says the cases may have been related to the vaccine.
In adults aged 65 years and older, RSV causes 6,000 to 10,000 deaths and 60,000 to 160,000 hospitalizations per year, according to the Centers for Disease Prevention. The risk of hospitalization increases with age, and adults aged 70 and over are more vulnerable.
Among adults of all ages hospitalized with RSV, 19% require intensive care and 4% die, according to three seasons of data from the CDC. Mortality is highest among the elderly.
GSK said the benefit the vaccine could provide in preventing RSV disease outweighs any potential risks.
“Our responsibility is to do what is right for society,” the doctor said. David Kim, US Public Health Officer and FDA committee member. “And in this case, we have a bad disease, we have a good vaccine. The vaccine can be used to prevent the disease,” he said.