A Food and Drug Administration advisory panel voted 16-2 Friday to advise the agency against approving a booster dose of the Pfizer-BioNTech Covid-19 vaccine.
The vote is non-binding, but it is an unexpected roadblock for the Biden administration’s plan to begin administering boosters widely as early as next week. Pfizer is seeking approval from FDA to offer the booster to people 16 and older, while Moderna has applied for authorization to market boosters for people 18 and older.
The advisory panel’s unexpected no vote came after an hourslong debate that centered on concerns about the amount and qualify of data available to weigh the booster’s long-term effectiveness and its safety in young people. The independent committee is now debating whether to endorse a more limited use of the Pfizer-BioNTech booster for older people and those who are considered to be at higher risk of severe disease because of their underlying health or occupational exposure.
The meeting comes amid heated debate among federal and outside scientists about whether evidence supports the Biden administration’s plan to begin rolling out boosters widely as early as next week. The FDA panel’s vote is not binding, but the agency normally usually follows the recommendations of its advisory committee. Should the FDA sign off on booster doses, a CDC expert panel will meet next week to iron out the specifics of who should receive boosters and when.
Peter Marks, FDA’s top vaccine regulator, asked committee members to examine “the totality of the evidence in order to make your recommendation for us,” including data from Israel showing that booster doses slashed the risk of severe Covid infections in its older population.
“The decision FDA needs to make is based on complex data evolving in front of our eyes,” he said. “There are different views. Differing opinions are critical to assisting in regulatory determination. It’s no secret here.”
But the panel’s independent members voiced concerns about the lack of data on the safety and efficacy of a booster dose for the general public, especially people younger than 60.
“While I would probably support a three-dose recommendation for those over 60 or 65, I really have trouble supporting this as written for anyone of greater than or equal to 16,” said Paul Offit of the Children’s Hospital of Philadelphia.
Several members raised concerns about the clear lack of data on the booster’s safety profile in young people, especially 16- and 17-year-olds.
“We have no data on the safety for this population at all,” said Archana Chatterjee, a pediatric infectious disease specialist at Rosalind Franklin University.
Such concerns arose early in the daylong meeting, when presenters and panel members alike expressed uncertain about whether there was clear evidence that boosters provide a benefit to younger people as well as to older people, whose immune systems are generally weaker, and whether there is sufficient safety data to move forward with a broad booster launch. Much of the concern centered on relatively rare instances of heart inflammation reported in recipients of the Pfizer-BioNTech and Moderna shots, which both rely on mRNA technology.
Sara Oliver, a doctor with CDC’s National Center for Immunization and Respiratory Diseases, said that vaccines’ efficacy against Covid infections and mild illness has dropped in the last few months. But it remains high against severe disease and hospitalization.
“Reasons for lower effectiveness likely include both waning over time and Delta variant,” which is more than twice as contagious as previous variants, Oliver said.
Pfizer representatives told the FDA panel that maintaining high vaccine effectiveness is integral to containing the pandemic, positing that more instances of severe disease and hospitalization are likely in the U.S. if the country doesn’t begin administering boosters to get ahead of the curve. The company argues that the effectiveness of its vaccine wanes over time, and that the rise of the Delta variant is not a major consideration in decisions on boosters.
Pfizer’s stance leans in large part on data from Israel on booster performance in people over 60; the country has expanded its vaccine campaign to include boosters for people over 30. In a separate presentation, Israeli scientists suggested that their country would have exceeded hospital capacity over the summer had it not begun giving boosters.
But FDA clinical reviewer Joohee Lee said the data from Pfizer’s own clinical trial to support the booster’s effectiveness is limited given the small number of participants and the unknown impact of factors like behavioral changes on the results. The safety data is also limited with respect to reactions by age, she said, noting that just a dozen trial participants between the ages of 65 and 75 got booster doses.
Separately, the CDC published data on Friday showing that all three Covid-19 vaccines available in the United States — from Pfizer-BioNTech, Moderna and Johnson & Johnson — still provide strong protection against hospitalization. The agency’s study, published in its Morbidity and Mortality Weekly Report, included information on more than 3,600 adults hospitalized at 21 U.S. facilities from March to August.
The agency found that the Moderna vaccine’s effectiveness against hospitalization was 93 percent, compared to 88 percent for the Pfizer-BioNTech shot. The effectiveness of the Pfizer-BioNTech vaccine declined significantly after 120 days, the CDC’s report said, although it still provided strong protection against severe disease.
And a Pfizer-sponsored analysis published Wednesday found that the vaccine’s efficacy against severe disease remained stable at nearly 97 percent over six months. The data came from an ongoing trial of more than 45,000 people in six countries who received the company’s two-dose initial vaccination regimen.
Tensions over the booster debate were palpable in opening statements delivered by two senior FDA officials, one of whom signed onto an essay published in The Lancet this week arguing that boosters are not immediately needed for most adults.
Earlier in the day, Marks urged the committee to focus on the science behind the booster application “and not on operational issues related to a booster campaign or on issues related to global vaccine equity” — adding that any forays into those topics would be interrupted.
“We know that there may be differing opinions as to the interpretation of the data regarding the potential need for additional doses, and we strongly encourage all the different viewpoints to be … discussed regarding the data, which is complex and evolving. It also requires near real-time analyses,” he said.
Marion Gruber, the retiring director of FDA’s Office of Vaccines Research and Review, said she looked forward to a “robust and transparent and evidence-based discussion.” The scientists who wrote the Lancet essay argued the existing science doesn’t support boosting the general population just yet, especially when much of the world has yet to receive their initial shots.
“All of my actions and decisions over my 32-year FDA career have been grounded in science and with you in mind and in the best interest of your health and safety, and I will continue to hold fast to these principles moving forward,” she said.
Scientists from FDA and other institutions this week suggested that the Israeli data contained several limitations that could make it difficult to underpin a regulatory decision in the U.S.
“I honestly don’t think there is enough good quality data at this point to make an informed decision,” Brittany Kmush, an epidemiologist at Syracuse University, said of the Israeli study, noting the 12-day follow-up period and the variability of the authors’ estimates.
Walid Gellad, director for the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh, said he hopes FDA and its advisers push Pfizer and others on the safety data from both the company and Israel. He pointed to the lack of direct safety data on additional doses given to 16- and 17-year-olds.
“The question for me is not do the boosters have some effect. The question is how much of an effect they have,” he said. “I’m not sure the Israeli data is giving us enough certainty about that.”
Some Biden health officials have suggested the Israeli data makes a strong case for permitting boosters in the U.S., given that the country is several weeks ahead regarding Covid trends.