A group of advisers to the Food and Drug Administration met Thursday to review an application from Pfizer and BioNTech for emergency approval of their coronavirus vaccine.
Results from a large study of nearly 44,000 volunteers showed the shot to be 95% effective in preventing COVID-19, a finding that FDA scientists affirmed in largely supportive documents released earlier this week. Thursday's meeting, though, was an important opportunity for independent vaccine and infectious disease experts to publicly vet the data gathered by Pfizer and BioNTech.
Should the committee back the companies' vaccine, an emergency use authorization from the FDA is expected to quickly follow.
BioPharma Dive tracked the nine-hour meeting and reported on the discussion here, with the most recent entries listed first.
The committee voted 17-4, with one abstention, to recommend approval of the vaccine. The vote was not without minor late-day drama, as several committee members objected to the inclusion of 16 and 17 year olds in the recommendation.
The data on that age group was the "thinnest" presented by the FDA and the drugmakers, argued committee member Archana Chatterjee, vice president for medical affairs at Rosalind Franklin University and one of the no votes. In addition, the objectors argued consent for this age group was given by their parents, and noted they don't get sick as often as older people.
On the other hand, 16 and 17 year olds are often more at risk of exposure because of their jobs, or could get exposed to the virus when they go off to college, said the advocates for keeping the recommendation broader.
Joining Chatterjee in voting no was Michael Kurilla of the National Institutes of Health, Oveta Fuller of the University of Michigan, and David Kim of the Department of Health and Human Services' office of infectious diseases and HIV. — Jonathan Gardner
Pfizer and BioNTech are initially seeking clearance to vaccinate people 16 or older. But Bill Gruber, a Pfizer executive in vaccine research and development, provided new details on how the companies aim to gather enough evidence to inoculate children as well.
Gruber said Pfizer already enrolled some 12 to 15 year olds in its Phase 3 trial, and noted the side effect profile it's observed so far "looks quite good" compared to adults. If things continue to go well, Pfizer will begin a study in children aged five to 11 years old by April, and then in children under five afterwards.
Gruber indicated Pfizer may not need to do a "dose-ranging" test in five to 11 year olds — a stepwise, cautious way to test escalating doses of a new drug — given the positive signs it's seen in adolescents. But "we're going to be very judicious," he said, "and work our way down." — Ben Fidler
Questioned by advisory committee member Paul Offit, of the Children's Hospital of Philadelphia, Pfizer revealed more information about the U.K. vaccine recipients who had severe allergic reactions.
A Pfizer representative said one had a history of food allergies, including eggs, and the other a history of drug allergies. Both recovered after treatment in the hospital where they received their shots.
Marion Gruber, director of FDA's vaccines review office, said the draft prescribing information they plan to publish following an emergency approval will include warnings against using the vaccine in people with a history of allergic reactions. The label under consideration would also require that vaccination occur in places where medical personnel can intervene in the case of any reaction.
Offit urged the FDA to conduct a safety study in patients with a history of allergies to learn more about the risk. "There are tens of millions of people who carry EpiPens," Offit said, referring to a leading treatment for acute allergic reaction. — Jonathan Gardner
One day after two allergic reactions prompted the U.K.'s drugs regulator to warn against giving the shot in people with a history of such episodes, the FDA said it's asking Pfizer and BioNTech to add anaphylactic reactions to its plan for safety monitoring.
Anaphylactic reactions are typically a rare side effect of vaccines. But with hundreds of millions of doses soon to go into humans, this side effect, if substantiated, will need to be closely watched.
Allergic reactions are one of three main concerns of Pfizer and BioNTech's "pharmacovigilance" plan, which is designed to address questions that couldn't be fully answered in the two months of safety follow-up they've provided so far.
Vaccine-associated enhanced disease — a condition in which immune proteins stimulated by vaccination can actually make disease worse — has been on the mind of the FDA and its expert advisers. And regulators want more information on vaccine use in pregnant and lactating women as well as adolescents and children, neither of whom were included in the clinical trial. — Jonathan Gardner
Pfizer and BioNTech's vaccine is given as two shots, spaced three weeks apart. Measuring seven days after the second dose, investigators running the companies' Phase 3 trial determined efficacy against COVID-19 was 95%.
But how effective is a single shot? The question is particularly important because of Pfizer and BioNTech's limited supply: Only some 50 million doses are expected to be available globally this month, or enough for 25 million people.
Study data appear to show protection begins about 11 days after the first dose, although determining true one-shot efficacy is impossible because most participants received a second shot at day 21.
Juan Gea-Banacloche, a consultant for the Mayo Clinic and an advisory committee panelist, pressed Pfizer officials on whether one dose is protective
"Protection was most mature, and was highest, after two doses were given," said Pfizer's Kathrin Jansen. "Since we started the study with two doses, we of course cannot predict how a single dose would affect persistence of protection."
Currently, the U.S. is planning to reserve enough doses to ensure everyone who gets their first shot will receive a second 21 days later. — Ned Pagliarulo
We know Pfizer and BioNTech's vaccine, as well as a rival shot from Moderna, are both strongly effective at preventing symptomatic COVID-19. But what about asymptomatic infections, which contribute heavily to the spread of the coronavirus?
Those data are apparently just around the corner. During Pfizer's presentation, Kathrin Jansen, Pfizer's head of vaccine R&D, said that data should be available "very soon in the new year."
Moderna president Stephen Hoge, meanwhile, has told BioPharma Dive the biotech will share data on whether its vaccine can prevent infection as soon as possible, potentially at an advisory panel meeting scheduled for next week.
So far, the only trial data on possible vaccine protection from infection comes from Astrazeneca and the University of Oxford, but the results are complicated by a dosing error. — Ben Fidler
Clinical trials are typically overseen by a group of advisers who, in theory, stand at arm's length from the study sponsor.
Called data monitoring committees, these groups review safety data and decide whether to stop testing for signs of harm or great benefit.
With their Phase 3 trial, Pfizer and BioNTech chose to use their own DMC rather than one organized by the U.S. government under its "Operation Warp Speed" program.
This group was who, on Nov. 9, declared Pfizer and BioNTech's trial a success, having determined the vaccine was "more than 90%" effective in preventing COVID-19.
Pfizer's presentation on Thursday gave us a glimpse at who makes up this panel: four infectious disease experts and one statistician, who met as recently as last week. At no point has the group identified any safety concerns. — Ned Pagliarulo
The public comment period was punctuated by Evan Fein, who participated in the Phase 1 trial of Pfizer and BioNTech's vaccine at New York University. He said he believes he received an active dose, not a placebo, because of mild side effects he had, and praised the clinical trial investigators who checked on his condition.
"Nothing felt rushed and I never felt like a guinea pig," he said.
In the months since, he has returned to normal activities like caring for his parents, exercising in small groups and going to his workplace in person, all of which he was doing prior to getting a shot, without getting COVID-19.
He concluded by invoking the spirit of passengers of Flight 93, who perished on 9/11 while fighting terrorists who had hijacked the plane.
"An EUA must be granted and it must be granted tonight," he said. "As of yesterday, the daily death toll for COVID-19 exceeds the death toll on Sep. 11, 2001. Delays on December 10 will mean more death on January 10. In the words of Todd Beamer, 'Let's roll.'" — Jonathan Gardner
Should trial volunteers who were initially given a placebo receive Pfizer and BioNTech's vaccine? If so, when?
Steven Goodman, a Stanford University professor, went through the many implications of these questions and the thorny ethical issues involved. Among them: Are volunteers who got a placebo, for instance, entitled to get the vaccine earlier than they otherwise would because they enrolled? Can that be done while ensuring Pfizer and BioNTech's trial — and, potentially other coronavirus vaccine studies — aren't compromised?
Pfizer and BioNTech offered one solution. They aim to give their shot to placebo patients who are eligible for vaccination according to CDC guidelines should they ask for it and then, after six months, all placebo patients.
Goodman argued, however, that while "not unreasonable," that plan would unblind all trial participants, change peoples' behavior, and "many of the benefits of randomization would be lost."
Instead, Goodman proposed an alternative, called "blinded crossover. "All placebo participants would get the vaccine, and vice versa, and none would know which they received and when. Doing so, Goodman argued, would help maintain the trial's integrity and the trust between sponsors and study participants.
Panelists had several questions about Goodman's presentation. Expect a lot of discussion on the topic this afternoon. — Ben Fidler
A 30-minute break before the open public hearing portion of the meeting starts at noon.
Pfizer and BioNTech have outlined how they plan to continue the massive clinical trial that got their vaccine to this point. But the CDC is also planning to track people who receive the vaccine outside of the study, too.
Across the U.S. government, there are five passive reporting programs for side effects that will feed into the safety database for the vaccine. On top of that, the CDC is implementing an active, text-based surveillance system called V-Safe, which will look for any adverse reactions experienced by vaccine recipients who opt in, said Nancy Messonnier, director of a CDC center on vaccines and respiratory diseases.
The government also wants to confirm whether the reported 95% vaccine efficacy reported in Pfizer and BioNTech's trial will hold up under real-world conditions, as well as assessing whether the shot can prevent infection.
First up will be a study of healthcare workers that will measure the likelihood of testing positive for coronavirus among those who didn't get a vaccine compared to those who did. The CDC also plans to use government data to study disease in high-risk subpopulations, and will conduct an analysis of viral transmission and mutations as more people are vaccinated. — Jonathan Gardner
The rate of weekly hospitalizations for COVID-19 in the U.S. is higher than at any other point since the pandemic began, Aaron Hall, an epidemiologist from the CDC told the committee.
A sharp rise in hospital visits among adults older than 65 is driving this surge, Hall said, but rates are increasing across all age groups. More than 282,000 Americans had died from COVID-19 through Dec. 8.
Hall's presentation is a reminder of the stakes at Thursday's panel. Pfizer and BioNTech's vaccine, the companies' study data show, can prevent many, if not most, COVID-19 cases, and protect against the disease's worst effects.
An emergency authorization would give public health officials a powerful tool to help curb COVID-19's spread and, likely, save lives. — Ned Pagliarulo
The minute the advisory panel began, the New England Journal of Medicine published the full results of the landmark Phase 3 trial that led to Pfizer and BioNTech's approval application.
The results of the study are potentially world-changing, the first from a large placebo-controlled trial to show a vaccine could strongly protect against COVID-19.
An accompanying editorial from the NEJM's editor-in-chief, Eric Rubin, and deputy editor Dan Longo, noted the trial's limitations and questions ahead for researchers, echoing many of the same points raised by the FDA in its briefing documents. Nonetheless, "the trial results are impressive enough to hold up in any conceivable analysis," they wrote. "This is a triumph."
Rubin's input, in particular, is notable: he's a voting member of the advisory panel. — Ben Fidler
Arnold Monto, the acting chair of the advisory committee, kicked off Thursday's proceedings, which will run through the early evening if the committee keeps to their agenda.
In the morning, Doran Fink, a deputy director in the FDA division that oversees vaccines, will overview the emergency use authorization process, and a Centers for Disease Control and Prevention official will give an update on coronavirus epidemiology.
One morning presentation, from Stanford University School of Medicine Steven Goodman, should be important: He'll be discussing considerations for running a placebo-controlled vaccine trial should one be authorized for emergency use — relevant for Pfizer and BioNTech as well as other developers.
In the afternoon, we'll hear from the companies themselves and then the FDA. A committee discussion starts at 3:10, followed by voting. — Ned Pagliarulo
The advisory panel gathering virtually on Thursday is large, with 13 temporary members joining the ten who typically sit on the committee. Seven regular members, including the chair, who stepped aside because she's overseeing a coronavirus vaccine trial, are not attending.
The panelists are mostly vaccine and infectious disease experts, many of whom are from academic institutions or large medical centers. There will also be a biostatistician, an epidemiologist and industry and consumer representatives.
Several experts who attended an October advisory committee meeting on coronavirus vaccine development generally are missing from Thursday's line-up, however, noted the Project on Government Oversight.
Officials from the FDA and the Centers for Disease Control and Prevention will speak but are not on the committee. — Ned Pagliarulo
The FDA is asking panelists to vote on just one question: whether the benefits of vaccination with Pfizer and BioNTech's vaccine outweighs the risks in people aged 16 years or older.
Support from a majority of panelists, which is widely expected, would almost certainly pave the way for an emergency authorization from the agency. The FDA typically, though not always, sides with its advisory panels.
The FDA is also asking the committee to discuss Pfizer and BioNTech's plans to offer study participants who received placebo the choice to get their vaccine, should an authorization be granted. Doing so might make it harder to track the vaccine's safety and protection over time, a point on which the agency wants the committee's input.
More broadly, the panelists are asked to discuss any gaps in the plans presented to them Thursday for further evaluation of the vaccine. This point is important as responses to the vaccine in the real world could differ from the more monitored environment of a clinical trial.
The FDA analysis posted this week also suggested one vaccine dose may be somewhat effective, although less so than two. Committee members may discuss that evidence, which could be important during early roll-out of the shot. — Ben Fidler
Pfizer and BioNTech have proven that a two-shot regimen of their vaccine is strongly effective at preventing adults from developing symptomatic COVID-19, regardless of age, race or ethnicity. Data from the companies' large Phase 3 trial also indicates the shot can protect against the disease's worst effects, although the evidence is less definitive.
Crucially, vaccination appeared safe, with no serious or unexpected side effects. Most people, though, experienced symptoms like fever, fatigue and headache, particularly after the second dose.
The results are highly encouraging and are very likely enough to secure an emergency approval from the FDA. But there's a lot we still don't know, most importantly how long protection will last and whether vaccination prevents infection or asymptomatic disease.
Pfizer and BioNTech also didn't study their vaccine in many adolescents, and children were excluded from the trial. The shot isn't yet proven safe and effective in women who are pregnant or nursing, or people with weak immune systems.
While the companies' Phase 3 study was large by clinical trial standards, rare or new side effects could still emerge once the shot is given to millions of people. Within the first day of authorization in Britain, for instance, UK regulators warned people with severe allergies not to get vaccinated, after two healthcare workers had anaphylactic reactions. Such reports are likely to be frequent amid mass immunization campaigns, but many may not end up being linked to the vaccine. — Ben Fidler
