The U.S. Food and Drug Administration on Tuesday released a 53-page report summarizing data from Pfizer and BioNTech’s COVID-19 candidate vaccine trial. The data supports earlier findings that the vaccine is safe and will prevent 95% of people from becoming sick with COVID-19.
The companies are asking the FDA for authorization to use the vaccine in people ages 16 and up. They have also begun testing the vaccine in ages 12-15, but have not yet accumulated enough data to request authorization in that age group.
The FDA panel that must review the vaccine before authorization meets all day Thursday, with authorization expected as soon as that evening. Another candidate vaccine, made by Moderna, will be reviewed next week.
Dr. William Schaffner, an infectious disease expert at the Vanderbilt University School of Medicine in Nashville, Tennessee, said he recently received a briefing on the Pfizer/BioNTech data, though he would not say who presented it or who else received it.
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“The group I was with who heard the data arrived interested and left the presentation enthusiastic,” Schaffner said. “The extraordinary thing is that there were no major areas of concern.”
Others also seemed impressed by the results.
“FDA did not note any surprise finding,” said Dr. John Grabenstein, a former Merck executive and former director of US Department of Defense military immunization program. The efficacy and product quality look good, Grabenstein said in an email, and there were few severe cases of COVID-19 in the vaccine group.
The report provides more detail on how certain groups of people fared with the vaccine, called BNT162b2, including people over 65, those with pre-existing medical conditions, like diabetes, and those who are Black and/or Hispanic – all of whom appeared to be as well protected as the general population.
Roughly one-third of participants met the definition of obesity, lower than the general population of the United States, but still high. The average age of participants was 51. They appeared to be as well or better protected than everyone else, countering the concern that the vaccine might not work as well in people who are older or who have conditions that might make them more vulnerable to serious disease.
The report also noted that the first vaccine dose seemed to be 52% protective, although because everyone received a second dose three weeks after the first, there’s no evidence of protection lasting longer than a few weeks.
With other vaccines, a second or booster shot extends the protection they provide.
“We don’t want to just get you through the night,” Schaffner said, adding that he’d rather be pleasantly surprised if the vaccines are shown to work after just one dose than unpleasantly surprised by people getting sick who stopped at their first shot.
Many trial participants endured side effects for a day or two after getting their shots, particularly the second one. The most commonly reported side effect among vaccine recipients under age 55 was a sore arm, followed by fatigue (60% after the second shot); headache (52% after the second shot); other muscle aches (37%); and chills (35%). About 28% took pain medication after the first shot and 45% after the second shot.
There were “no surprises” in terms of safety, Grabenstein noted. Four people in the vaccinated group developed Bell’s palsy – a temporary weakness of muscles in the face that causes one side to droop or stiffen – but that may or may not have been caused by the vaccine, and the FDA referred to the cases as “non-serious.”
Other “serious adverse events” were reported in both groups, including two deaths among those who received the active vaccine and four among placebo recipients, but they were unlikely to be related to the vaccine, the report concluded.
Overall, the FDA report concluded the data “meets the agency’s expectations … The frequency of non-fatal serious adverse events was low (less than .5%), without meaningful imbalances between study arms.”
The study also noted that Pfizer/BioNTech will offer BNT162b2 to anyone who received the placebo if they request it, and to all placebo recipients six months after their second dose.
Pfizer/BioNTech will continue to study these trial participants and will also undertake several new studies to follow people who receive the vaccine after it is authorized, according to the report.
While the vaccine has been shown to be safe among the 22,000 people who received it, rare health complications are likely to arise as it is used in hundreds of thousands and then millions of people.
Despite the thoroughness of the report, there are still unanswered questions.
Among the big ones:
How long will the vaccine last?
FDA will consider “authorizing” this vaccine, but will not issue a full approval because there is no data on how long the vaccine will be protective.
Officials decided that in the midst of a pandemic, it was good enough to ensure that the vaccine was safe and at least transiently effective, rather than withholding it for two years to await the typical long-term results required for a full approval.
Vaccine companies intend to follow trial participants for two years and submit a full application when they have that data.
The FDA noted in the report that Pfizer/BioNTech must periodically review the safety of their vaccine, including breakdowns by age, special populations, such as pregnant women, and serious adverse events.
Does the vaccine prevent infection or just symptoms?
Right now, all we know is that the Pfizer/BioNTech and Moderna candidate vaccines prevent COVID-19 symptoms and serious disease. It’s not clear whether someone could catch the virus that causes COVID-19 and pass it on to someone else, even without becoming ill.
The studies designed to test the candidate vaccines only examined symptomatic infections, not whether vaccinated people could still be contagious.
This means that people who are vaccinated can be pretty sure that they won’t develop COVID-19 themselves, but they could still pass it on to others without knowing they are infected.
Regulatory officials thought it was more important in the middle of a deadly pandemic to prevent sickness and didn’t want to slow down trials by adding extra requirements. Future studies will explore this.
“That’s one of the reasons you’ll still have to keep wearing your masks and social distancing,” said Schaffner, who was not involved in developing any of the COVID-19 candidate vaccines, but has followed the process closely. Proving that vaccines prevent transmission, he said “would have taken much longer, much more money and might have (required a) much larger trial.”
He defended the decision to focus on preventing disease rather than worrying about transmission.
“We would like to keep people out of the hospital, out of the intensive care unit and not subject to the risk of dying,” he said. “I’ll take that.”
Early indications from a study released Tuesday in The Lancet suggest that the AstraZeneca/Oxford University candidate vaccine at least partially prevents a vaccinated person from transmitting the disease.
Could the vaccine make subsequent infections worse?
There has been concern that getting vaccinated against COVID-19 might cause a subsequent COVID-19 infection, as some dengue vaccines have been shown to do for that disease.
The FDA concluded that use of the vaccine has not been widespread enough to know for certain, but that “available data do not indicate a risk of vaccine-enhanced disease, and conversely suggest effectiveness against severe disease within the available follow-up period.”
The risk does remain over time as immunity against the disease wanes, the FDA said, and “needs to be evaluated further in ongoing clinical trials.”
What about children and pregnant women?
The data only included children ages 16 and up, though the study has since been extended to age 12, and will include younger children as soon as the company decides what dose it wants to test in this group.
Pregnant and nursing women were not included in the study, so there is no data to suggest whether they should avoid vaccination. In a meeting last week of a CDC group that determines how vaccines should be allocated, several expert members said they expected the vaccine would be safe for mothers who are nursing because the virus itself does not seem to pass through the mother’s milk.
Overall, Schaffner said, the process of developing and testing the candidate vaccine will look simple in comparison to the challenges of delivering it to a country of 328 million and beyond.
It will be, he said, “a much larger, longer, intensive, expensive effort and will require great commitment, great persistence, great communication.”
Other new studies Pfizer/BioNTech plans to conduct include: a survey of 20,000 U.S. health care workers enrolled in the COVID-19 HERO registry, among others; and a 30-month-long study using data from the Department of Defense Health System electronic health records to examine vaccine results among covered U.S. military and their families. The companies also will look for any adverse events associated with the vaccine using the Veterans Health Administration electronic medical record database.