I understand that endorsing and approving are the same thing.
So why can't you understand this, straight from the horse's mouth.
FDA advisory panel endorses Pfizer/BioNTech Covid-19 vaccine
By STAT staff Dec. 10, 2020
Reprints
ADOBE
Apanel of outside experts on Thursday recommended the Food and Drug Administration issue an emergency use authorization to the Covid-19 vaccine being developed by Pfizer and BioNTech, a vaccine that appeared to be highly efficacious in a Phase 3 clinical trial.
The
17-4 vote came after a long day in which members of the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, discussed a wide range of issues related to the vaccine, including concerns about vaccinating people with severe allergies and 16- and 17-year-olds, as well as issues regarding vaccination during pregnancy or lactation.
Although the FDA does not have to follow the panel’s recommendation, it is widely expected to do so.
The rollout of Covid-19 vaccine could then begin in the United States in a matter of days.
STAT’s coverage of the meeting is below, with updates and analysis posted in reverse chronological order.
NEWSLETTERSSign up for Daily Recap
A roundup of STAT's top stories of the day.
Privacy Policy
A positive vote, but a missed opportunity
6:30 p.m.: By any account, today’s vote — again, 17 yes, four no, with one abstention — was a resounding thumbs up for granting an emergency use authorization for the Covid-19 vaccine developed by Pfizer and BioNTech.
But to anyone who has followed many FDA advisory meetings, the conclusion of this one was surprising, and not in a good way. The final vote seems to have been influenced by one narrow issue: the inclusion of 16- and 17-year olds in the proposed emergency use authorization. Oddly, the FDA declined to reword the question — something the FDA has done in the past during in-person advisory committee meetings — when some panelists protested the inclusion of people younger than 18.
We don’t really know why the panelists voted as they did, though. Surprisingly, there was no opportunity for them to explain their vote afterward. Such comments are often every bit as important as the actual vote.
The purpose of these committees — and of waiting for them — is to delve into nuance. On that score, too many opportunities were missed.
— Matthew Herper
Coda: We need to talk about the kids
6:20 p.m.: A late afternoon dust up over teenagers may at least partially explain four negative votes and one abstention when VRBPAC members voted on the question of whether the FDA should issue an EUA to allow use of Pfizer’s vaccine in people ages 16 and older.
Several members of the committee expressed serious concerns about including 16- and 17-year-olds in the EUA, saying Pfizer has very little data on the vaccine’s safety in this group. The data package the company filed for its EUA application included only 153 participants 16 and 17 years old. (More recently the company has been vaccinating children as young as 12 years of age, but those data weren’t in the EUA filing.)
“I would support not including them,” Hayley Gans, a professor of pediatrics at Stanford University, said during a section of the overall discussion where multiple members of the committee raised concerns about including that group.
Multiple, but not all.
“We have clear evidence of a benefit. All we have on the other side is theoretical risk,” said Paul Offit, a pediatrician at Children’s Hospital of Philadelphia.
Acting chairman Arnold Monto, a vaccines researcher from the University of Michigan, called on FDA’s Marion Gruber, director of the Office of Vaccines Research and Review, for advice. She said she wanted to hear from the rest of the committee, so Monto called the vote.
Several of the committee members — Gans among them — who had advocated excluding 16- and 17-year-olds ended up voting to recommend approval of vaccine. One, Cody Meissner, a pediatrician at Tufts Children’s Hospital, abstained. There was no call for an explanation of why dissenters voted no — and STAT hasn’t had time yet to reach out to them — but at least one, Archana Chatterjee, vice president for medical affairs at Rosalind Franklin University, had indicated she would have voted to raise the age covered by an EUA to 18 years old.
— Helen Branswell
The vote
5:37 p.m.: After eight-plus hours of data presentations, discussion and debate, today’s Covid vaccine advisory panel finally got down to voting on the penultimate 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?
The results:
17 Yes, 4 No, 1 abstention.
And with that, the FDA will very likely grant an emergency use authorization to the Pfizer/BioNTech Covid vaccine within days, if not sooner.
One thing to watch: There was a lot of disagreement among the panel members about whether the data support the inclusion of people 16-17 years of age in the EUA. Will FDA make changes to the EUA to exclude this group?
— Adam Feuerstein
Pfizer pushes back against “crossover” design for placebo patients
5:05 p.m.: Earlier in the day, there was an enthusiastic presentation of a proposal that tried to allow volunteers who had received placebo to receive the vaccine while minimizing the problems this would present for collecting new data about the vaccine.
The idea, summarized by Helen this morning, is that all volunteers would get two more shots. Those who had received placebo would get the vaccine; those who got the vaccine would get placebo.
But William Gruber, a Pfizer senior vice president, pushed back on this idea. It was, he pointed out, potentially impractical. “44,000 individuals would have to be brought in for two additional visits,” he noted. That means they would need to sign new consent forms. And, if they already suspected they received the vaccine because they noticed aches or chills, they might decide not to come in for those additional visits. Gruber has said previously that he is worried that volunteers will leave the study if they are not offered the vaccine, and that he will not get data from them at all.
In an email earlier today, a Pfizer spokesperson confirmed the company is not currently planning to use the crossover design.
“The participants in our COVID-19 vaccine clinical trial are courageous volunteers who have made a personal and important choice to help make a difference during this pandemic,” Pfizer said in a statement. “We also believe that we have an ethical duty to create a pathway within the study for interested, eligible participants in the placebo group to have access to the vaccine as regulatory authorities make decisions about authorization or approval of the vaccine candidate around the world.”
Pfizer added: “In turn, we have developed a protocol amendment that is subject to input from and alignment with regulatory authorities but is designed so that all interested participants 16 years and older in the placebo group would have the option to receive the vaccine at scheduled timepoints in the study.”
— Matthew Herper
What do we do about vaccinating people with severe allergies?
4:29 pm: A big question has emerged around the Pfizer-BioNTech vaccine: Two people in the U.K who received the vaccine had severe allergic reactions requiring treatment, leading regulators there to advise that people with severe allergies should not get the vaccine for the time being.
Paul Offit, the noted vaccinologist from Children’s Hospital of Philadelphia and a panelist at today’s meeting, pointed out that this is a potentially big problem. It means that tens of millions of Americans, by his count, could be too afraid to get the vaccine because they have a medical history of severe allergy. Offit was clear that he did not think this should stand in the way of an EUA, but he said that Pfizer and BioNTech needed to do a study in people with a history of common allergies and asked the FDA what it planned to do.
“This issue is not going to die until we have better data,” Offit said.
Marion Gruber, director of the office of vaccines research and review at the FDA, said that the FDA had note of this possibility even before the two cases in the U.K. Weeks ago, she said, language was added to a draft EUA warning that people who had an allergy to any of the vaccine’s components should not get it, and that equipment for dealing with a severe allergic reaction should be available wherever the vaccine is administered.
Gruber also said that an independent analysis by the FDA had pointed to the possibility of some volunteers in the trial potentially having allergic reactions that researchers had not caught, although all of those would have been minor, by definition.
But Offit pointed out that with this vaccine, which he said had one of the longest chemical names he’d ever seen, patients would have trouble identifying potential allergens from the ingredients list. He also clarified that his main worry, perhaps caused by years of discussions with people who were vaccine hesitant, was as much about people’s fears as the vaccine’s characteristics.
“I’m talking about perception more than reality,” Offit said. “With those two statements out there, that people with severe allergic reactions shouldn’t get the vaccine, we just really need to offer people some solace.”
— Matthew Herper
Showtime!
3:50 p.m.: The meeting, which is currently running about 40 minutes behind schedule, is about to get down to brass tacks.
The session in which members will discuss what they’ve heard and vote on whether the FDA should issue an emergency use authorization for Pfizer’s Covid vaccine begins now.
If you want to check the meeting out yourself, it’s streaming
here.
— Helen Branswell
During Pfizer presentation, anxiety and excitement commingle
2:55 p.m.: In a sense, Pfizer’s presentation to the VRBPAC was a victory lap, as Kathrin Jansen, the company’s head of vaccine research, took a moment to explain how an mRNA vaccine mimics the body’s normal immune response. A piece of mRNA is shepherded into a cell by a coating of fat, called a lipid nanoparticle. It does not, likely, get all the way to the nucleus, where the DNA is, so the mRNA is unlikely to ever have a long-term effect. But it makes a protein that is part of the virus, without any risk of viral infection.
Amid all the science, though, Jansen emphasized that vaccines may be “the only way to return to normal lives.”
The presentation conveyed both the tremendous potential and the impressive results that Pfizer and its partner BioNTech have demonstrated so far and some nagging questions. One of these has to do with whether the vaccine prevents severe cases of Covid-19 or hospitalizations. Pfizer simply has fewer of these severe cases in its trial than does Moderna, which is presenting results at an FDA panel meeting in a week. And one case logged as severe disease was in the vaccine group.
Related:
‘How are we going to get on that plane?’: The transatlantic race to deliver CAR-T cancer therapy during the pandemic
William Gruber, the Pfizer executive who presented the company’s data, described lots of alternative ways of cutting these data aimed at calming any nerves. First, he noted, this one case only counted as severe for one reason — a brief drop in blood oxygen levels. And, using different definitions of severe disease from the one favored by the FDA, there were more cases in the placebo group and they did worse.
But at least one panelist seemed to have a different question: Do we even need to use two doses? Juan Gea-Banacloche, a Mayo Clinic epidemiologist, asked how confident Pfizer is that the second dose is even needed. Pfizer replied, basically, that there isn’t enough evidence to conclude a vaccine would give the same long-term protection as two doses.
Pfizer also leaked out some news related to when we’ll have answers to some important vaccine questions. Data on how well the vaccine protects against asymptomatic infection — that is, Covid-19 cases with no symptoms — is expected early next year. And, as Helen noted earlier, preclinical studies aimed at understanding potential development toxicities could deliver preliminary results in mid-December, which could mean within days.
— Matthew Herper
Some news on vaccination during pregnancy or lactation
1:55 p.m.: As Covid-19 vaccine rollout nears, a key question has been: Should pregnant and lactating people be vaccinated? There are no data on which to base an answer, but some may be on the way.
The FDA told vaccine manufacturers they had to do what are called DART studies — that’s short for developmental and reproductive toxicity studies — before they could conduct clinical trials to test if these vaccines are safe to use in pregnancy and during breastfeeding. DART studies are done in animals, looking to see if there are any signs a vaccine might hurt a developing fetus or pose a threat to the pregnancy.
None of the vaccine manufacturers near the front of the vaccine pipeline has completed DART studies. But on Thursday, Pfizer told the VRBPAC meeting it expects preliminary results from its DART studies in Wistar rats by mid-December — in other words, within days.
The company will still have to do trials in people who are pregnant and lactating before the FDA would agree to specifically authorize the vaccine for these populations. But experts on the issue of drug and vaccine testing during pregnancy have urged the agency not to close the door to use in these groups in the meantime. In an
opinion piece published Wednesday in STAT, they argued that the FDA should allow the vaccine to be offered to pregnant and lactating people, and let them decide whether they want to be vaccinated.
Vaccination in the United States could begin within days, and health care workers are at the front of the line. About 75% of health care workers are women and a large portion of them are of child-bearing age. The CDC estimates that at any given time, about 330,000 health care workers are either pregnant or lactating.
— Helen Branswell
Public hearing elevates vaccine hesitancy issue
1:45 pm: Vaccine hesitancy was on full display during the one-hour open public hearing, as multiple speakers raised concerns about the safety of the Pfizer/BioNTech vaccine and the legitimacy of granting early authorization based on limited data.
The skeptical comments, some of which veered uncomfortably close to dangerous conspiracy theories, underscore the challenge facing vaccine makers and public health officials in convincing Americans to get vaccinated against Covid-19.
One speaker, who described herself as a mother of a child who she said was “injured” by routine childhood vaccinations, urged the FDA to disclose all the ingredients that go into the Covid vaccine, including “aborted fetal cells” — a false claim.
Another speaker, a pediatrician from Florida who said he does not require his patients to get routine vaccines, highlighted potential safety risks that some people might experience if they get vaccinated.
Several other speakers voiced concerns that the clinical trial conducted by Pfizer and BioNTech was rushed, or that certain participant groups, particularly people of color, were underrepresented in the clinical database. The 44,000-patient clinical trial enrolled a diverse patient population in terms of race and ethnicity, age, and underlying health conditions. About 26% of participants were identified as Latino and 10% as Black, with the study evenly split between men and women.
To be clear, these panels are not meant to be coronations of clinical data without anyone asking appropriately probing questions. But these days, distinguishing healthy skepticism from damaging anti-vaccine tropes is increasingly difficult. The FDA wants to encourage transparency in the review process to enhance vaccine confidence, but by doing so, it also opens up the possibility of amplifying people with the opposite agenda.
Sidney Wolfe, founder and senior advisor of Public Citizen’s Health Research Group, gave testimony during the open public hearing, expressing his support for the emergency use authorization of the Pfizer/BioNTech Covid vaccine. Wolfe is notorious for opposing almost every new drug that comes in front of the FDA, so his support shows that even perma-skeptics can be convinced that vaccine makers are doing something right.
— Adam Feuerstein
www.latimes.com
