This 1981 photo provided by the Centers for Disease Control and Prevention (CDC) shows an electron micrograph of respiratory syncytial virus, also known as RSV.
CDC via AP
The Food and Drug Administration sees a possible 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 injection is approved this spring, according to agency documents released Friday.
Two people in their 60s who received the Pfizer injection were diagnosed with Guillain-Barre syndrome, out of about 20,000 vaccine recipients in the third phase of the study. according to an FDA document. There were no cases in the placebo group, people who did not receive the injection.
Guillain-Barre syndrome, or inflammatory neuropathy, is a rare disorder in which the body’s immune system mistakenly attacks nerves. Symptoms range from brief weakness to paralysis, according to the State Institute of Health. Most people recover, even from severe cases.
Pfizer, in its information document, said the cases have other possible explanations. However, it said it would conduct a safety study to further assess Guillain-Barre syndrome after possible approval. The company said it found no safety concerns during the study and the vaccine was well tolerated.
There was also a possible case of Guillain-Barre syndrome in GSKstudy of the RSV vaccine, but the company said there was insufficient evidence to confirm the diagnosis. GSK listed Guillain-Barre as an important potential risk in its safety surveillance plan, according to the FDA. The agency said it will review the plan and make recommendations as needed.
The FDA has released briefing papers ahead of advisory committee meetings next week. 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 vaccine against RSV. The virus causes 6,000 to 10,000 deaths a year in the elderly, although the death rate varies from season to season.
The Pfizer vaccine was 85% effective in preventing lower respiratory tract disease, and the GSK vaccine was 83% effective, according to an FDA review of the data.
Cases of Guillain-Barré
In a Pfizer study, a 66-year-old US man with a history of hypertension developed Guillain-Barre symptoms seven days after vaccination. The man had a heart attack before the onset of symptoms, was hospitalized and underwent angioplasty. The FDA does not consider heart attack to be related to the RSV vaccine.
The man developed pain in the lower back eight days after vaccination and then on the 14th day he experienced weakness in the lower limbs. After the fall, he was re-hospitalized and subsequently diagnosed with Guillain-Barre syndrome. His symptoms began to improve after treatment and resolved six months after onset, according to the FDA.
In the 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 the vaccination, she experienced fatigue, a sore throat on the second day, and poor muscle control on the 10th day. She was hospitalized 19 days after the vaccination, but her symptoms completely resolved within three months.
The FDA said it agreed with investigators that the cases were likely related to the Pfizer vaccines. However, Pfizer provided other possible explanations in its briefing paper. 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 since 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 an important potential risk in its safety surveillance.
“Given the temporal context and biological plausibility, FDA agrees with the investigators’ assessment that these events may have been related to the study vaccine,” the agency said.
In the GSK case, a 78-year-old woman in Japan developed leg weakness nine days after receiving the first dose of 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 upper limb and respiratory muscle weakness over the next three days. She was hospitalized and treated for Guillain-Barre syndrome. The FDA and the study investigator consider the case to be related to the vaccine.
However, GSK said in its briefing paper that the diagnosis of Guillain-Barre was not confirmed due to the absence of test 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.
CDC advisors grapple with the risks and benefits
The Centers for Disease Control and Prevention’s Independent Advisory Committee on Immunization dealt with three cases of Guillain-Barre syndrome during a meeting open to the public Thursday. Dr. Michael Melgar, a CDC official, told the committee that it is difficult to determine whether the cases represent a real safety issue related to the gunshots or if they are random events.
“Due to the small number of events, relative and absolute risk rates were not calculated,” Melgar told committee members.
But a a working group of doctors and health officials who reviewed the available data agreed that safety monitoring will be essential if the vaccines are to be approved by the FDA, Melgar said.
Most members of the task force believed that the potential benefits of the vaccines outweighed the possible risks for people age 65 and older, Melgar said. A minority believed that the risk-benefit ratio was uncertain in part because of Guillain-Barre cases.
Although Pfizer and GSK petitioned the FDA for approval of their respective vaccines for those 60 years of age and older, the CDC task force generally favored recommendations for seniors 65 years of age and older. A CDC advisory committee did not vote on any RSV vaccine recommendations this week.
Dr. Sarah Long, a member of the task force, said the cases gave her pause because the incidence of Guillain-Barre syndrome increases with age, meaning seniors may be at higher risk if a link to the vaccine is found at some point.
Dr. Grace Lee, chairwoman of the CDC’s advisory committee, said more data is needed because respiratory viral illnesses also cause Guillain-Barre syndrome. It is possible that vaccines could prevent further cases of Guillain-Barre syndrome by protecting against illness from RSV.
“Maybe you’re preventing more and we don’t know for sure what the rate is, but I just think that balance is going to be really helpful, at least for me, to be able to understand how to think between benefit and risk. balance,” said Lee, associate chief medical officer at Stanford Children’s Health. “Then I’ll understand if the 60s or 65s make sense or not.”
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