FDA advisors recommend GSK-RSV vaccine but point to potential safety issues

The Food and Drug Administration’s independent advisory panel recommended on Wednesday GlaxoSmithKline RSV vaccine for adults 60 years and older, although they highlighted potential safety issues related to nervous system disorders that could be related to vaccination.

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

The panel came to a similar conclusion Tuesday on Pfizer’s filing for approval of its RSV vaccine in a narrow 7-4 vote. While the consultants incorrectly recommended approval, they also raised concerns about a possible link to Guillain-Barré syndrome. In this vote, one scientist abstained.

Respiratory syncytial virus kills thousands of seniors every year. There is currently no approved vaccine against RSV. GSK injection is given as a single dose of 120 micrograms.

Both companies have asked the FDA to approve their RSV vaccine for adults age 60 and older. The agency is expected to make its decision on GSK’s vaccine by May 3, with Pfizer’s response also expected this month. GSK and Pfizer’s respective vaccines are set to become the world’s first approved vaccines to prevent the virus.

According to an FDA review of the company’s data, GSK’s vaccine was approximately 83% effective in preventing RSV-related lower respiratory tract disease during the study. Illness was defined as two additional symptoms, including shortness of breath, wheezing, coughing, increased mucus production, crackling, low oxygen saturation, or need for oxygen supplementation.

GSK had no data on how long protection from the vaccine lasts and how it works in people with compromised immune systems, according to the FDA.

“These data are robust and show potentially very high efficacy against lower respiratory disease,” said Dr. Amanda Cohn, committee member and chief medical officer at the National Center for Immunizations and Respiratory Diseases.

However, the advisers discussed at length risks of rare diseases of the nervous system that may be linked to the vaccine. GSK said it is closely monitoring safety concerns during trials and will continue to do so after potential approval.

dr Hana El Sahly, the chair of the committee, said more safety data is needed before approval. There was one case of Guillain-Barre in the study, and two people developed another rare nervous system disorder after receiving both the RSV and flu vaccines, one of which died. dr Marie Griffin, who is also a member of the panel, agreed that more data is needed.

“I just don’t understand why there is such a rush to get this vaccine approved now,” said Griffin, a physician at Vanderbilt University Medical Center.

Guillain-Barre case

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

GSK said there was insufficient evidence to confirm a diagnosis. The FDA believes the case is vaccine-related.

Guillain-Barré 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-Barre syndrome were diagnosed during Pfizer’s RSV vaccine trials. Griffin said the fact that such a rare condition appeared in both companies’ studies was disturbing.

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Griffin noted that Johnson & Johnson recorded a case of Guillain-Barre during its Covid vaccine trial. The FDA finally issued a warning for the J&J vaccine after noting an increased rate of the disease. Large clinical trials of Pfizer’s and Moderna’s Covid vaccines have had no Guillain-Barre cases, she said.

“It’s not something you see routinely in one or two cases,” said Griffin, an FDA committee member who voted “no” to the safety of the shot but “yes” to its effectiveness.

dr Nicholas Geagan, an FDA official, agreed that the Guillain-Barre cases in the GSK and Pfizer studies are troubling. GSK has agreed to expedited reporting of cases of illness, Geagan said.

“It seems worrying to have observed these cases as part of a clinical development program,” Geagan told the committee. “That’s why we are discussing with the sponsor about the further development of future safety analyzes from GBS.”

The FDA said in a briefing document that the rate of Guillain-Barre syndrome in older adults is about 1 in 100,000 in people over the age of 60. In GSK’s study, it was closer to 1 in 15,000.

dr Ann Falsey, a professor of medicine at the University of Rochester, told the panel that the rate of the Guillain-Barre system increases with age and there are other studies that put the rate at 8 to 12 per 100,000 for people over the age of 65 years and older. Falsey attended GSK’s presentation to the committee.

dr Peggy Webster, head of vaccine safety at GSK, said the rate of Guillain-Barré syndrome is higher in Japan, where the study participant who developed the disease lives.

Death during process with RSV and flu shots

There were also two cases of another nervous system disorder, including one death, during a GSK study in which the RSV and flu vaccines were given together. The patients developed what is known as acute disseminated encephalomyelitis, a sudden inflammation in the brain and spinal cord. These were the only cases of the disorder among 15,000 vaccinated recipients.

The FDA said the cases may be related to either GSK’s RSV vaccine or the flu shot that was administered with it.

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A 71-year-old man developed the neurological disorder seven days after receiving RSV and influenza vaccines. He was taken to hospital after being found lying on the ground shaking and shaking. He died 22 days after receiving the shots.

A woman of the same age suffered from headaches with double vision, forgetfulness, shaking hands and uncoordinated movements. She showed improvement, but her symptoms hadn’t completely gone as of the last update, according to the FDA.

El Sahly, the FDA committee chair, said the rate of this neurological disorder is typically 0.1 in 100,000 patients, mostly in children.

“So two cases in elderly people three to four weeks after vaccination is highly anomalous from a statistical point of view,” said El Sahly, who voted “no” to safety but voted “yes” to efficacy.

Adam Berger, an official with the National Institutes of Health, said he viewed the acute cases of disseminated encephalomyelitis as being related to the concomitant administration of RSV and the flu shot rather than a problem with GSK’s vaccine.

“I suggest relying heavily on post-marketing surveillance and not just relying on it, but making sure there is enforcement of the requirements to actually do it,” said Berger, who is a member of the FDA committee .

There have also been two cases of Bell’s palsy, which is a weakness or paralysis on one side of the face. There was also a case of Graves’ disease, or overproduction of thyroid hormone, a case of gout, and a case of a skin condition called psoriasis.

A report from the FDA said the cases may be related to the vaccine.

In adults age 65 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 Control Prevention. The risk of hospitalization increases with age, and adults 70 and older are more susceptible.

According to three seasons of CDC data, 19% of adults of all ages hospitalized with RSV require critical care and 4% die. Mortality is highest among the elderly.

GSK said the benefits the vaccine would offer in preventing RSV disease outweighed any potential risks.

“Our duty is to do what is right for the public,” said Dr. David Kim, a U.S. Health and Human Services official and a member of the FDA committee. “And in this case we have a bad disease, we have a good vaccine. The vaccine could be used to prevent disease,” he said.

Correction: The 71-year-old man who received the RSV and flu vaccines developed symptoms seven days after receiving the vaccination. He died on the 22nd day. In a previous version, the time to onset of symptoms was reported incorrectly. dr Ann Falsey of the University of Rochester said Guillain-Barre syndrome increases with age, with some studies putting the rate at 8 to 12 per 100,000. In a previous version, the rate was incorrect.