FDA says Guillain-Barre syndrome is a possible risk of the Pfizer RSV vaccine

The Food and Drug Administration sees a potential risk of Guillain-Barre syndrome with Pfizer’s RSV vaccine for older adults and has asked the company to conduct a safety study if the shot is approved this spring, according to the agency’s briefing documents. published Friday.

According to the FDA document, two people in their 60s who received Pfizer’s shot were diagnosed with Guillain-Barre syndrome, out of about 20,000 vaccine recipients in the phase three trial. There were no cases in the placebo group of the trial, the people who didn’t get the shot.

Guillain-Barre syndrome, or inflammatory neuropathy, is a rare condition in which the body’s immune system mistakenly attacks the nerves. Symptoms range from brief weakness to paralysis, according to the National Institutes of Health. Most people recover, even from severe cases.

Pfizer said in its briefing paper that the cases have other possible explanations. But it said it will conduct a safety study to further assess Guillain-Barre syndrome after potential approval. The company said it had not identified any safety concerns during the trial and that the vaccine was well tolerated.

There was also a possible case of Guillain-Barre syndrome in GSK’s RSV vaccine trials, but the company said there was not enough evidence to confirm a diagnosis. According to the FDA, GSK has listed Guillain-Barre as a major potential risk in its safety oversight plan. The agency said it will review the plan and make recommendations as needed.

The FDA released the briefing documents ahead of advisory committee meetings next week. The advisers will vote Tuesday on whether Pfizer’s efficacy and safety data support FDA approval. They will also vote on GSK’s RSV vaccine for older adults on Wednesday.

There is no approved RSV vaccine. The virus causes between 6,000 and 10,000 deaths per year among seniors, although mortality varies from season to season.

Pfizer’s vaccine was 85% effective in preventing lower respiratory tract disease and GSK’s vaccine was 83% effective, according to an FDA review of the companies’ data.

In the Pfizer study, a 66-year-old man in the US with a history of hypertension developed Guillain-Barre symptoms seven days after vaccination. The man had a heart attack before symptoms started, was admitted to hospital and underwent angioplasty. The FDA does not consider the heart attack related to the RSV vaccine.

The man developed lower back pain eight days after vaccination and on the 14th day he felt weakness in his lower extremities. He was hospitalized again after a fall and was subsequently diagnosed with Guillain-Barre syndrome. His symptoms began to improve after treatment and disappeared six months after starting, according to the FDA.

In a second case, a 66-year-old woman in Japan with a history of type 2 diabetes developed a severe case of Miller Fisher syndrome, a variant of Guillain-Barre. Nine days after vaccination she experienced fatigue, a sore throat the next day and poor muscle control by day 10. She was hospitalized 19 days after vaccination, but her symptoms completely resolved within three months.

The FDA said it agrees with investigators that the cases may have been related to Pfizer’s vaccines. But Pfizer said in its briefing paper that there are other possible explanations. The company pointed to the man’s heart attack and said the woman had symptoms of an upper respiratory infection.

But the FDA said that given the incidence of Guillain-Barre syndrome in the general population is about 3 cases per 100,000 people per year, Pfizer should consider the incidents as a major potential risk in its safety oversight.

“Given the temporal association and biological plausibility, the FDA agrees with the investigators’ assessments that these events may have been related to the study vaccine,” the agency said.

In the case of GSK, a 78-year-old woman in Japan developed weakness in the lower extremities nine days after receiving the first dose of the RSV vaccine, according to an FDA briefing paper. She participated in an open-label study without a placebo arm for comparison.

The woman had difficulty walking the next day and developed weakness of the upper extremities and respiratory muscles over the next three days. She was hospitalized and treated for Guillain-Barre syndrome. The FDA and the study investigator consider the case related to the vaccine.

But GSK said in its briefing paper that a Guillain-Barre diagnosis was not confirmed due to the lack of research results and because there was no information on whether alternative causes had been investigated. The patient’s case was considered resolved after six months, the company said.

The Centers for Disease Control and Prevention’s committee of independent vaccine advisers grappled with the three cases of Guillain-Barre syndrome at a public meeting Thursday. Dr. Michael Melgar, a CDC official, told the committee it is difficult to determine whether the cases represent an actual safety issue associated with the injections, or whether they are random events.

“Because of the small number of events, relative and absolute risks were not calculated,” Melgar told committee members.

But a working group of doctors and health officials who reviewed the available data agreed that safety monitoring will be critical if the vaccines are approved by the FDA, Melgar said.

A majority of the working group believed the potential benefits of the vaccines outweigh the potential risks for people age 65 and older, Melgar said. A minority believed that the risk-benefit balance was uncertain, in part due to the Guillain-Barre cases.

While Pfizer and GSK have asked the FDA to approve their respective vaccines for people age 60 and older, the CDC working group has generally favored a recommendation for seniors age 65 and older. The CDC advisory committee did not vote on recommendations for the RSV vaccines this week.

Dr. Sarah Long, a member of the task force, said the cases made her think because the incidence of Guillain-Barre syndrome increases with age, meaning seniors may be at greater risk if there is an association at some point is found with the vaccine.

Dr. Grace Lee, the chair of the CDC advisory committee, said more data is needed because respiratory viral illnesses also cause Guillain-Barre syndrome. It is possible that the vaccines could prevent more cases of Guillain-Barre syndrome by protecting against disease from RSV.

“Maybe you’re preventing more, and we’re not sure what the rate is, but I just think that balance is going to be really helpful, at least for me to understand how to think through the benefit-risk balance,” said Lee, associate chief medical officer at Stanford Children’s Health. “Then I can understand whether the 60-year-olds or the 65-year-olds make sense.”

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