The FDA’s vaccine advisory committee voted 17-4 with one abstention Dec. 10 to recommend an emergency use authorization (EUA) for the Pfizer Inc./Biontech SE mRNA vaccine BNT-162b2 to prevent COVID-19 in individuals 16 and older.
The yes vote would have been higher had the indication excluded 16- and 17-year-olds, as some panelists were concerned about the paucity of data for that age group since they were added late to the phase III trial.
Noting that COVID-19 infections aren’t a big problem in that age group, panelist Cody Meissner, director of pediatric infectious disease at Tufts Medical Center, said he was uncomfortable with including 16- and 17-year-olds in the indication because he didn’t think there was enough data to determine whether the benefit of the vaccine outweighed the risks for them.
Archana Chatterjee, a dean at the Chicago Medical School and an expert in pediatrics and infectious diseases, shared his concerns. The data are thinnest for that age group, she said. While she thought the data also were thin for people older than 75, Chatterjee said the potential benefit for older people who are more at risk of serious infections outweighed her concerns about the lack of data for that subpopulation.
However, another pediatrician on the panel, Paul Offit, a professor at the Children’s Hospital of Philadelphia, supported inclusion of 16- and 17-year-olds in the indication, pointing out that they can get COVID-19 and some have developed cardiac anomalies because of the coronavirus. There is clear evidence of benefit for that age group, Offit said, adding that the risks of the vaccine are only theoretical.
Others on the committee noted that young people aren’t in the priority groups that will be among the first to be offered what will be limited supplies of the vaccine, so their inclusion on the label isn’t an issue. Health care workers and residents of long-term living facilities will be first in line.
The debate now goes to the FDA as it makes the decision on granting an EUA. Agency officials speaking at the adcom indicated they were comfortable with extrapolating data for 16- and 17-year-olds.
In expectation of an EUA being granted quickly, the U.S. CDC’s Advisory Committee on Immunization Practices (ACIP) has scheduled two emergency public meetings this weekend to consider the vaccine’s data.
Friday, ACIP will look at the development program, the vaccine profile and post-authorization safety monitoring plan. The group plans to meet again Sunday to discuss clinical considerations for the Pfizer/Biontech vaccine and to vote on recommendations for its administration.
The big question now is how soon the FDA will grant the EUA, as that will determine how quickly the most vulnerable people can begin getting the vaccine. Speaking at an Operation Warp Speed (OWS) briefing a few weeks ago, Health and Human Services Secretary Alex Azar said the vaccine could be distributed throughout the U.S. within 24 hours of FDA authorization, with administration beginning as soon as the product arrives.
In addition, he said CVS Health, one of the private-sector partners involved in the distribution/administration effort, expected to be vaccinating residents of nursing homes within 48 hours after FDA authorization.
Based on the number of vaccine doses manufactured as of mid-November, General Gustave Perna, the chief operating officer for OWS, said he expected about 3 million doses to be distributed within the first week of an EUA.
Citing Pfizer’s current production schedules, Azar said OWS expects to “have enough doses to vaccinate 20 million Americans by the end of the year, 50 million total by the end of January and at least 100 million total by the end of the first quarter.” And by the end of the second quarter of 2021, there should be enough doses to vaccinate any American who wants it.
Meanwhile, Pfizer and Biontech will continue with a hefty clinical program as they expand the populations being studied and do long-term follow-up to gather the data needed to turn the EUA into a biologic license application, which the FDA is expecting to be submitted in the next three or four months.
To get two years’ of follow-up data, Pfizer is proposing to urge participants to stay in the trial as long as possible, while unblinding those on placebo who want the vaccine. The blind would be maintained for others in the trial.
The ethics and feasibility of continuing blinded, placebo-controlled trials once an EUA has been granted was one of the issues the adcom wrestled with Thursday. The FDA had Steven Goodman, associate dean of clinical and translational research at Stanford University School of Medicine, present a blinded crossover design in which trial participants in the vaccine arm would receive a placebo and those in the control arm would get the vaccine – but only when the vaccine would be available for their population group. In other words, it wouldn’t allow them to jump the queue ahead of people with higher risk when vaccine supplies are limited.
William Gruber, senior vice president for vaccine clinical R&D at Pfizer, acknowledged there were some potential advantages with the blinded crossover, but it would require twice as many people to come in for two additional visits – that could be an additional 88,000 visits. It also would require reconsenting all the participants.
In addition, Gruber questioned whether participants would be willing to come back for the additional visits. Because of the high incidence of minor reactions in people who received the vaccine in the trial, those participants likely would know they had received the vaccine and they might not be willing to return twice to get a placebo at a time when COVID-19 is surging.