The Food and Drug Administration’s independent advisory panel on Wednesday really helpful by GlaxoSmithKline RSV vaccine for adults aged 60 years and over, although they noted potential safety issues with nervous system disorders that could be related to vaccination.
Ten FDA advisors said the safety data for the GSK vaccine was adequate and two said it was not. The committee unanimously concluded that the data on the effectiveness of the vaccine were sufficient.
The panel reached an analogous conclusion on Tuesday by a narrow vote of seven to 4 on Pfizer’s request to remove the RSV vaccine. While advisors made the mistake of recommending approval, in addition they expressed concern a few possible link to Guillain-Barre syndrome. One scientist abstained.
Respiratory syncytial virus kills hundreds of seniors annually. There’s currently no approved vaccine against RSV. GSK injection is given as a single dose of 120 micrograms.
Each firms have applied to the FDA for approval of the RSV vaccine for adults 60 and older. The agency is anticipated to make a choice on GSK’s vaccine by May 3, with Pfizer’s response also expected this month. The respective GSK and Pfizer vaccines could turn out to be the world’s first approved vaccines to prevent the virus.
The GSK vaccine was about 83% effective in stopping RSV-induced lower respiratory disease in the trial, according to an FDA review of knowledge. Disease was defined as two additional symptoms, including shortness of breath, wheezing, coughing, increased mucus secretion, crackles, low oxygen saturation, or the need for oxygen supplementation.
According to the FDA, GSK had no data on how long protection from the vaccine lasts or how it really works in individuals with weak immune systems.
“These data are robust and show potentially very high efficacy against lower respiratory disease,” said Dr. Amanda Cohn, committee member and chief physician at the National Center for Immunizations and Respiratory Diseases.
Nonetheless, advisors have discussed intimately the risk of rare nervous system disorders which are believed to be related to the vaccine. GSK said it was closely monitoring safety issues during the trials and would proceed to accomplish that after potential approval.
Dr Hana El Sahly, chair of the committee, said more safety data was needed before approval. There was a case of Guillain-Barre in the study, and two people developed one other rare nervous system disorder after receiving each the RSV vaccine and the flu vaccine, one in all whom died. Dr Marie Griffin, who can be on the panel, agreed that more data was needed.
“I just don’t understand why there is a rush to approve this vaccine now,” said Griffin, a physician at Vanderbilt University Medical Center.
Guillain-Barre case
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 lady was the only case of Guillain-Barre syndrome out of 15,000 individuals who received the injection.
GSK said there was not enough evidence to confirm the diagnosis. The FDA believes the case is said to the vaccine.
Guillain-Barre syndrome is a rare neurological disorder whose symptoms range from weakness to paralysis. According to the National Institutes of Health, most individuals recuperate even after severe cases.
During trials of Pfizer’s RSV vaccine, two cases of Guillain-Barre syndrome were diagnosed. Griffin said the indisputable fact that such a rare disorder occurred in each firms’ studies was concerning.
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Griffin noted that Johnson & Johnson recorded one case of Guillain-Barre during a trial of a Covid vaccine. The FDA eventually issued a warning for the J&J injection after finding an increased incidence of the disease. She said large clinical trials of Pfizer and Moderna’s Covid vaccines showed no cases of Guillain-Barre.
“It is not something you routinely see in a single or two cases,” said Griffin, an FDA committee member who voted “no” to the safety of the injection but “yes” to its effectiveness.
Dr. Nicholas Geagan, an FDA official, agreed that the Guillain-Barre cases in the GSK and Pfizer trials were concerning. GSK has agreed to expedited reporting of cases of the disease, Geagan said.
“There appears to be concern about seeing these cases in the context of a clinical development program,” Geagan told the committee. “So we’re discussing with the sponsor on the further development of further GBS safety studies.”
The FDA in a briefing document stated that the prevalence of Guillain-Barre syndrome in the elderly is roughly 1 in 100,000 amongst people 60 years of age and older. In the GSK study, it was more like 1 in 15,000.
Dr. Ann Falsey, professor of medication at the University of Rochester, told the panel that the incidence of Guillain-Barre syndrome increases with age, with other studies putting the rate at 8 to 12 per 100,000 people aged 65 and over. Falsey attended GSK’s presentation to the committee.
Dr Peggy Webster, head of vaccine safety at GSK, said the incidence of Guillain-Barre syndrome is higher in Japan, where the study participant who developed the disease lives.
Death during trial with RSV and flu vaccines
There have been also two cases of one other nervous system disorder, including one death, during a GSK trial during which RSV and influenza vaccines got together. The patients developed what known as acute disseminated encephalomyelitis, a sudden attack of inflammation in the brain and spinal cord. These were the only cases of the disorder amongst 15,000 vaccine recipients.
The FDA said the cases are likely related to GSK’s RSV vaccine or the flu vaccine that was given with it.
A 71-year-old man developed a neurological disorder seven days after receiving the RSV and influenza vaccine. He was hospitalized after being found lying on the floor shaking and shaking. He died 22 days after receiving the shots.
A girl of the same age suffered from headaches with double vision, forgetfulness, trembling hands and uncoordinated movements. According to the FDA, she has shown improvement, but her symptoms haven’t completely cleared since the last update.
El Sahly, chairman of the FDA committee, said the incidence of this neurological disorder is often 0.1 per 100,000 patients, mostly amongst children.
“So the two cases in the elderly three to 4 weeks after vaccination are highly anomalous from a statistical point of view,” said El Sahly, who voted against safety but for efficacy.
Adam Berger, an official at the National Institutes of Health, said he considered cases of acute disseminated encephalomyelitis to be likely related to the simultaneous administration of RSV and influenza vaccines, not the GSK vaccine.
“I suggest a heavy reliance on postmarketing surveillance, and never just relying but ensuring there may be an enforcement requirement to actually do them,” said Berger, who’s a member of the FDA committee.
There have been also two cases of Bell’s palsy, which is weakness or paralysis of 1 side of the face. There was also a case of Graves’ disease or overproduction of thyroid hormones, a case of gout, and a case of a skin condition called psoriasis.
The FDA staff report said the cases were likely related to the vaccine.
According to the Centers for Disease Control Prevention, in adults aged 65 and older, RSV causes 6,000 to 10,000 deaths and 60,000 to 160,000 hospitalizations annually. The chance of hospitalization increases with age, with adults aged 70 and over being more in danger.
Amongst adults of all ages hospitalized for RSV, 19% require intensive care and 4% die, according to CDC data for 3 seasons. Mortality is highest amongst seniors.
GSK said the advantages the vaccine would offer in stopping RSV disease would outweigh the potential risks.
“It’s our responsibility to do what’s good for society,” said Dr. David Kim, a U.S. public health official and FDA committee member. “And on this case, we’ve a foul disease, we’ve a great vaccine. The vaccine could be used to prevent the disease,” he said.
Correction: A 71-year-old man who received RSV and influenza vaccines developed symptoms seven days after receiving the injections. He died on day 22. The previous version incorrectly stated the time to onset of symptoms. Dr. Ann Falsey of the University of Rochester said that Guillain-Barre syndrome increases with age, with some studies putting the rate at 8 to 12 per 100,000. The previous version got the rate improper.