Post by icemandios on Dec 11, 2020 16:45:38 GMT
December 10, 2020 05:55 PM ESTUpdated 10 hours ago
Advisory committee votes 17-4 to recommend FDA authorize Pfizer-BioNTech vaccine, opening door to rapid EUA
Jason Mast
Editor
There were a million questions but little suspense.
For eight and a half hours, a panel of outside advisors debated Pfizer’s vaccine data, questioned endpoints, poked holes in post-authorization plans, interrogated safety signals and debated sub-groups, but in the end voted as most expected them to: recommending the FDA should okay Pfizer and BioNTech’s mRNA-based vaccine as the first inoculation for Covid-19 in the U.S.
The final vote was 17-4, with the strongest debate coming over whether there was enough data to authorize the vaccine for 16 and 17 year olds. “Among all the scientific data presented, I though that the thinnest was for the 16 and 17 year olds,” said Archana Chatterjee, the dean of the Chicago Medical School, who voted no. One member of the committee abstained.
The vote likely points to an emergency use authorization within days —or even hours —for the vaccine, marking a turning point in the pandemic and kicking off the complicated and arduous task of distributing limited doses across a country embroiled in the worst phase of the virus to date. Although the FDA is not required to follow the committee’s recommendation, it usually does.
If OK’d, 2.9 million doses of the vaccine, dubbed BNT162b2, would immediately be shipped across the country, with the government promising to distribute 20 million doses before the end of the month. A CDC committee will meet tomorrow to discuss who should get the vaccine first, although HHS Secretary Alex Azar has said states will have final say on the question.
Another advisory committee for Moderna’s mRNA vaccine, is scheduled for next Thursday. Pfizer said they are aiming to file for a full approval in April.
The committee and FDA representatives raised several key issues, including how to handle long-term follow up and what to do with placebo arms after an EUA, but members were only asked to vote on a single question: “Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?”
On that question, there was little debate. Participants raised concerns about rare safety issues in the trial, including four cases of Bell’s palsy — a form of temporary facial paralysis or weakness — that appeared in the vaccine arm, compared to zero in the placebo arm. And others wondered how rigorous the study’s endpoints were, noting they didn’t test whether the vaccine prevents asymptomatic infection and that their definition of a “severe” Covid-19 case didn’t require hospitalization or death.
A handful also drew attention to the subgroups, questioning how diverse the study was and whether there was enough data on how the vaccine could help people of color and people in nursing homes.
Yet, they noted the vaccine was 95% effective in preventing mild disease, as the companies announced and published today in the New England Journal of Medicine. At times, they prefaced tough questions around the vaccine with stipulations that the data is nonetheless overwhelmingly strong.
“I agree, the benefits outweigh the risks,” Paul Offit, director of the Vaccine Education Center at the Children’s hospital of Philadelphia, said as he proposed Pfizer do a new trial to address a safety concern. “I’m fine with it.”
And although they would have liked longer follow-up, they argued the two months follow-up was sufficient to show safety, particularly given the state of the pandemic in the U.S. Cody Meisner, a pediatric infectious disease physician, said in previous vaccine, virtually all adverse events appeared in the first 60 days.
“I think the safety is pretty well demonstrated,” he said. “And balance that against over 2,000 deaths a day, 2,500 deaths per day? I’m comfortable.”
Still, an EUA, if it arrives, will raise new questions. Most immediately: What should Pfizer do with its ongoing Phase III study? The FDA asked the committee to discuss but not vote on it.
In an October meeting, the committee was skeptical of Pfizer’s plan to offer a vaccine to the placebo group after an EUA was granted, fearing that it would prevent regulators from getting a good look at how safe and effective the vaccine was in the long-term. In their EUA application and new briefing documents, Pfizer specified they would only offer the vaccine to participants once CDC guidelines suggested they could get the vaccine — i.e. a participant who is a healthcare worker over 65 may receive it this month, while a 30-year-old analyst may be offered in March.
The FDA, in its own review, emphasized the need to continue trials, and officials noted that a long-term placebo group can help illuminate not only what adverse events a vaccine causes, but also what adverse events are not attributable to the vaccine.
But Steven Goodman, associate dean of clinical and translational research at the Stanford University School of Medicine, offered the committee an alternative solution. It wouldn’t be unethical to keep the trials unblinded, he said, but it could become infeasible as more vaccines become publicly available. To avoid having volunteers drop out, he argued that the sponsors could give vaccine to the placebo group and placebo to the vaccine group, allowing investigators to still collect some randomized data on key issues like durability.
Pfizer vaccine executive William Gruber said the proposal had been “front and center” for them, but they determined the benefits may be overplayed and the logistics difficult. Some members of committee, though, appeared sympathetic to the view.
Committee members also emphasized the need for a long-term followup, noting they only had a median of two months follow-up on the participants. They fretted over how to communicate the side effects, such as fatigue and headache, that occur as the immune system kicks into gear, and questioned how the paucity of long-term data will affect uptake.
“There’s such a limited risk assessment that I think the uptake is going to be fairly poor, unless something better is done,” A. Oveta Fuller, an sssociate professor of microbiology immunology at the University of Michigan, asked.
The FDA also disclosed during the hearing that they had asked Pfizer to follow recipients for cases of anaphylactic reactions, an adverse event that occurred in the UK and prompted the regulators there to say no one with a history of severe allergic reactions from getting the vaccine.
The FDA’s Marion Gruber cautioned that the UK cases were not severe and said they would only recommend against people with a history of allergic reactions to ingredients in the Pfizer vaccine. But Offit argued that the UK incident and comments made immediately afterward by Operation Warp Speed chief Moncef Slaoui had made many with allergies concerned. He suggested they run a trial on patients with history of allergy.
“You’re talking about tens of millions of people who are not going to get a vaccine because of the comments that were made both by the UK and by the comments made by Moncef Slaoui here,” he said.
In their presentation, Pfizer disclosed plans to address key lingering questions around their vaccine’s efficacy. Within days, they said, they would finish the DART preclinical studies that would allow them to test the vaccine on pregnant people. And they said they plan to do a form of antibody testing that should tell them whether the vaccine protects against asymptomatic infection early in 2021.
Questions, though, came around the vaccine’s ability to prevent severe disease. Sheldon Taubman, an attorney and the consumer advocate on the panel, noted that the FDA’s internal review determined that Pfizer’s data — nine severe cases in the placebo group and one in the vaccine group — only suggested the inoculation can prevent the disease’s worst manifestations, rather than offer conclusive evidence.
“Frankly almost nobody cares about Covid-19 if all it does is give you a sore throat,” Taubman said. “The data is just not sufficient.”
Taubman proposed a limited EUA for healthcare workers and the elderly to allow Pfizer to collect more data on severe cases. But Doron Fink, deputy director of the FDA’s vaccine division, said that all their experience with previous vaccines suggesting protection against mild disease translated to protection against severe disease.
“Protection against disease of any severity is actually a pretty good predictor,” he said. “And the data that we do have is all pointing in the right direction.”
Advisory committee votes 17-4 to recommend FDA authorize Pfizer-BioNTech vaccine, opening door to rapid EUA
Jason Mast
Editor
There were a million questions but little suspense.
For eight and a half hours, a panel of outside advisors debated Pfizer’s vaccine data, questioned endpoints, poked holes in post-authorization plans, interrogated safety signals and debated sub-groups, but in the end voted as most expected them to: recommending the FDA should okay Pfizer and BioNTech’s mRNA-based vaccine as the first inoculation for Covid-19 in the U.S.
The final vote was 17-4, with the strongest debate coming over whether there was enough data to authorize the vaccine for 16 and 17 year olds. “Among all the scientific data presented, I though that the thinnest was for the 16 and 17 year olds,” said Archana Chatterjee, the dean of the Chicago Medical School, who voted no. One member of the committee abstained.
The vote likely points to an emergency use authorization within days —or even hours —for the vaccine, marking a turning point in the pandemic and kicking off the complicated and arduous task of distributing limited doses across a country embroiled in the worst phase of the virus to date. Although the FDA is not required to follow the committee’s recommendation, it usually does.
If OK’d, 2.9 million doses of the vaccine, dubbed BNT162b2, would immediately be shipped across the country, with the government promising to distribute 20 million doses before the end of the month. A CDC committee will meet tomorrow to discuss who should get the vaccine first, although HHS Secretary Alex Azar has said states will have final say on the question.
Another advisory committee for Moderna’s mRNA vaccine, is scheduled for next Thursday. Pfizer said they are aiming to file for a full approval in April.
The committee and FDA representatives raised several key issues, including how to handle long-term follow up and what to do with placebo arms after an EUA, but members were only asked to vote on a single question: “Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?”
On that question, there was little debate. Participants raised concerns about rare safety issues in the trial, including four cases of Bell’s palsy — a form of temporary facial paralysis or weakness — that appeared in the vaccine arm, compared to zero in the placebo arm. And others wondered how rigorous the study’s endpoints were, noting they didn’t test whether the vaccine prevents asymptomatic infection and that their definition of a “severe” Covid-19 case didn’t require hospitalization or death.
A handful also drew attention to the subgroups, questioning how diverse the study was and whether there was enough data on how the vaccine could help people of color and people in nursing homes.
Yet, they noted the vaccine was 95% effective in preventing mild disease, as the companies announced and published today in the New England Journal of Medicine. At times, they prefaced tough questions around the vaccine with stipulations that the data is nonetheless overwhelmingly strong.
“I agree, the benefits outweigh the risks,” Paul Offit, director of the Vaccine Education Center at the Children’s hospital of Philadelphia, said as he proposed Pfizer do a new trial to address a safety concern. “I’m fine with it.”
And although they would have liked longer follow-up, they argued the two months follow-up was sufficient to show safety, particularly given the state of the pandemic in the U.S. Cody Meisner, a pediatric infectious disease physician, said in previous vaccine, virtually all adverse events appeared in the first 60 days.
“I think the safety is pretty well demonstrated,” he said. “And balance that against over 2,000 deaths a day, 2,500 deaths per day? I’m comfortable.”
Still, an EUA, if it arrives, will raise new questions. Most immediately: What should Pfizer do with its ongoing Phase III study? The FDA asked the committee to discuss but not vote on it.
In an October meeting, the committee was skeptical of Pfizer’s plan to offer a vaccine to the placebo group after an EUA was granted, fearing that it would prevent regulators from getting a good look at how safe and effective the vaccine was in the long-term. In their EUA application and new briefing documents, Pfizer specified they would only offer the vaccine to participants once CDC guidelines suggested they could get the vaccine — i.e. a participant who is a healthcare worker over 65 may receive it this month, while a 30-year-old analyst may be offered in March.
The FDA, in its own review, emphasized the need to continue trials, and officials noted that a long-term placebo group can help illuminate not only what adverse events a vaccine causes, but also what adverse events are not attributable to the vaccine.
But Steven Goodman, associate dean of clinical and translational research at the Stanford University School of Medicine, offered the committee an alternative solution. It wouldn’t be unethical to keep the trials unblinded, he said, but it could become infeasible as more vaccines become publicly available. To avoid having volunteers drop out, he argued that the sponsors could give vaccine to the placebo group and placebo to the vaccine group, allowing investigators to still collect some randomized data on key issues like durability.
Pfizer vaccine executive William Gruber said the proposal had been “front and center” for them, but they determined the benefits may be overplayed and the logistics difficult. Some members of committee, though, appeared sympathetic to the view.
Committee members also emphasized the need for a long-term followup, noting they only had a median of two months follow-up on the participants. They fretted over how to communicate the side effects, such as fatigue and headache, that occur as the immune system kicks into gear, and questioned how the paucity of long-term data will affect uptake.
“There’s such a limited risk assessment that I think the uptake is going to be fairly poor, unless something better is done,” A. Oveta Fuller, an sssociate professor of microbiology immunology at the University of Michigan, asked.
The FDA also disclosed during the hearing that they had asked Pfizer to follow recipients for cases of anaphylactic reactions, an adverse event that occurred in the UK and prompted the regulators there to say no one with a history of severe allergic reactions from getting the vaccine.
The FDA’s Marion Gruber cautioned that the UK cases were not severe and said they would only recommend against people with a history of allergic reactions to ingredients in the Pfizer vaccine. But Offit argued that the UK incident and comments made immediately afterward by Operation Warp Speed chief Moncef Slaoui had made many with allergies concerned. He suggested they run a trial on patients with history of allergy.
“You’re talking about tens of millions of people who are not going to get a vaccine because of the comments that were made both by the UK and by the comments made by Moncef Slaoui here,” he said.
In their presentation, Pfizer disclosed plans to address key lingering questions around their vaccine’s efficacy. Within days, they said, they would finish the DART preclinical studies that would allow them to test the vaccine on pregnant people. And they said they plan to do a form of antibody testing that should tell them whether the vaccine protects against asymptomatic infection early in 2021.
Questions, though, came around the vaccine’s ability to prevent severe disease. Sheldon Taubman, an attorney and the consumer advocate on the panel, noted that the FDA’s internal review determined that Pfizer’s data — nine severe cases in the placebo group and one in the vaccine group — only suggested the inoculation can prevent the disease’s worst manifestations, rather than offer conclusive evidence.
“Frankly almost nobody cares about Covid-19 if all it does is give you a sore throat,” Taubman said. “The data is just not sufficient.”
Taubman proposed a limited EUA for healthcare workers and the elderly to allow Pfizer to collect more data on severe cases. But Doron Fink, deputy director of the FDA’s vaccine division, said that all their experience with previous vaccines suggesting protection against mild disease translated to protection against severe disease.
“Protection against disease of any severity is actually a pretty good predictor,” he said. “And the data that we do have is all pointing in the right direction.”