FDA advisor recommends GSK RSV vaccine, but flags potential safety risks

An independent panel of advisers to the Food and Drug Administration recommended on Wednesday glaxosmithkline RSV vaccine for adults age 60 and older, though he flagged potential safety issues over nervous system disorders that could be tied to the shot.

Ten FDA advisers said the safety data on GSK’s vaccine was sufficient, while two said it was not. The committee unanimously said that the data on the effect of the vaccine is sufficient.

The panel reached a similar conclusion Tuesday by a 7-to-4 vote on Pfizer’s application to approve the RSV vaccine. While the consultants erred in recommending approval, they also raised concerns over a possible link to Guillain-Barré syndrome. One scientist abstained from that opinion.

Respiratory syncytial virus kills thousands of senior citizens every year. There is currently no approved vaccine for RSV. GSK’s shot is given as a single dose of 120 micrograms.

Both companies have asked the FDA to approve their RSV shot for adults 60 and older. The agency is expected to take a decision on GSK’s vaccine by May 3, and Pfizer’s reply is expected in the same month. The respective vaccines from GSK and Pfizer have become the world’s first approved vaccines to prevent the virus.

GSK’s vaccine was about 83% effective in preventing lower respiratory tract disease caused by RSV during the trial, according to an FDA review of the company’s data. Disease was defined as two more symptoms including shortness of breath, wheezing, cough, increased sputum production, crackles, low oxygen saturation or the need for oxygen supplementation.

According to the FDA, GSK did not have data on how long protection from the vaccine lasts and how it performs in people with weakened immune systems.

But the advisors discussed longer risks of rare nervous system disorders possibly related to the vaccine. GSK said it is closely monitoring safety concerns during the trials and will continue to do so after possible approval.

A 78-year-old woman in Japan was diagnosed with Guillain-Barre syndrome nine days after receiving the GSK vaccine. She was discharged from the hospital six months after vaccination. The woman was the only case of Guillain-Barre syndrome out of 15,000 people who received the shot.

GSK has stated that there was not enough evidence to confirm the diagnosis. The FDA is considering the matter to be related to the vaccine.

Guillain-Barre syndrome is a rare neurological disorder with symptoms ranging from weakness to paralysis. According to the National Institutes of Health, most people recover even from severe cases.

Two cases of Guillain-Barré syndrome were diagnosed during Pfizer’s RSV vaccine trials. Dr. Mary Griffin, a physician at Vanderbilt University Medical Center, said the presence of such a rare error in the two companies’ tests is troubling.

Griffin noted that Johnson & Johnson reported a case of Guillain-Barre during its Covid vaccine trial. The FDA eventually issued a warning for J&J’s vaccine after detecting an increased rate of disease. He said there were no Guillain-Barre cases in the large clinical trials of the Covid vaccines from Pfizer and Moderna.

“It’s not something you regularly see in one or two cases,” said Griffin, an FDA committee member who voted yes on the shot’s safety but not on its efficacy.

Dr. Nicolas Gagnon, an FDA official, agreed that the Guillain-Barre cases in the GSK and Pfizer trials were troubling.

“It appears that these cases have been viewed in the context of a clinical development program,” Gegan told the committee. “We are therefore in discussions with the sponsor about the development of post-GBS safety analyses.”

The FDA said in a briefing document that the rate of Guillain-Barré syndrome in older adults is about 1 in 100,00 in people age 60 and older. In GSK’s trial, it was more than 1 in 15,000.

A professor of medicine at the University of Rochester, Dr. Ann Falci told the panel that the rate of Guillain-Barre system increases with age and that there are other studies that put the rate at 8 to 15 per 100,000. Falci participated in GSK’s 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 flu vaccines were given together. The patients developed something called acute disseminated encephalomyelitis, a sudden attack of inflammation in the brain and spinal cord. These were the only cases of disorder among 15,000 vaccine recipients.

The FDA said the cases are possibly related to GSK’s RSV vaccine or the flu shot supplied with it.

A 71-year-old man developed a neurological disorder 22 days after receiving the RSV and flu vaccines. He was admitted to the hospital after being found lying on the floor trembling and shaking. A female of the same age suffered double vision, amnesia, headache with shaking hands and uncoordinated movements. She showed improvement but according to the FDA, her symptoms had not completely resolved as of the last update.

FDA committee chair Dr. Hana El Sahli said the rate of this neurological disorder is typically 1 in 100,00 patients, mainly in children.

“The two cases in the elderly three to four weeks after the vaccine are highly disproportionate from a statistical point of view,” said El Sahli, who voted yes on efficacy, not safety.

There were also 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 overproduction of thyroid hormones, a case of gout, and a skin condition called psoriasis.

A report by FDA staff said the cases were possibly related to the vaccine.

According to the Centers for Disease Control and Prevention, among adults age 65 and older, RSV causes 6,000 to 10,000 deaths and 60,000 to 160,000 hospitalizations per year. The risk of hospitalization increases with age, and adults 70 and older are more vulnerable.

According to data from the CDC for three seasons, among adults of all ages hospitalized with RSV, 19% required intensive care and 4% died. The death rate is highest among senior citizens.

GSK said the benefits the vaccine would provide in preventing disease from RSV would outweigh any potential risks.