The FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) held its first COVID-19 vaccine meeting on Oct. 22. The live-streamed event featured presentations and questions from federal advisers, scientists, doctors and multiple medical groups.
As planned, the panel did not weigh in on any particular vaccine. Instead the nine-hour meeting focused on a range of topics, including the FDA’s approach to evaluating safety and efficacy data and an in-depth discussion about Emergency Use Authorization (EUA) designation.
Of the four potential vaccines now in active phase 3 trials in the U.S. — Pfizer/BioNTech, Moderna, J&J and AstraZeneca/University of Oxford — two of them (Pfizer and Moderna) are poised to have adequate data to support an EUA request in November — pushing the topic to the forefront of the discussion.
EUAs were widely discussed, with several panel members challenging the specifics of the FDA criteria for EUAs.
FDA released more robust guidance on Oct. 6, in spite of White House resistance. President Trump has called the new EUA guidance a “political move” and initially said the White House “may or may not approve it.”
During the committee meeting, concerns were noted over the proposal that drugmakers conduct a median two months of follow-up after study participants get their final dose of the vaccine before requesting an EUA. While there was broad agreement that data to support issuance of an EUA for a vaccine should not be less than the standards outlined in the updated guidance, some committee members felt this follow up was not adequate, suggesting four months of data.
A larger concern seemed to be considerations for continuation of blinded phase 3 trials if an EUA is issued for an investigational vaccine. Most agreed that blinded research should continue post-EUA if possible, but if not, follow-up studies are needed.
Office of Vaccines Research and Review (OVRR) Director Dr. Marion Gruber highlighted the issue, mentioining the “risk that use of a vaccine under an EUA would interfere with long-term assessment of safety and efficacy in ongoing trials and potentially even jeopardize product approval.”
Some committee members suggested the possibility that trial participants, fearing they had received a placebo, could drop out of the trial if a vaccine is available through an EUA, thus eliminating the trial’s control arm. Enrollment in trials for other COVID-19 vaccines could slow down if people have the opportunity to get vaccines through an EUA and don’t want to risk ending up in a trial’s placebo group.
But on the flip side, if the trial is unblinded and participants in the placebo group are offered a vaccine, it could skew the results of the study.
Vaccine confidence was also an important part of the meeting discussion, as the pharma industry and health officials continue to grapple with declining public trust.
Gruber emphasized how critical it is to “build trust and confidence in the use of COVID-19 vaccines by the general public and the medical community.” During a presentation discussing the National Institutes of Health activities related to the development of COVID-19 vaccines, NIAID’s Dr. Hilary Marston outlined what is being done to improve confidence in Operation Warp Speed trials, including study safeguards, transparency and communication.
Dr. Peter Lurie, who formerly served as an FDA associate commissioner, testified before the VRBPAC, asking that the committee make its independence from political pressures clear, reiterating a commonly expressed concern about the politicized vaccine approval process. “A vaccine that is not accepted is an ineffective vaccine. The only antidotes to public mistrust are transparency and scientific rigor. I urge this committee to be their staunchest advocate,” said Lurie.
With minority and elderly populations dying at a disproportionate rate throughout the pandemic, diversity has been an important discussion point.
The importance of making sure that minorities are included in clinical studies was brought up frequently during the meeting. But with many trials nearing their endpoints, it may be a concern highlighted too late. Temporary voting member on the committee, Dr. Michael Nelson, president of the American Board of Allergy and Immunology and a physician at Walter Reed National Military Medical Center, asked the FDA to clarify how an EUA would be handled in situations where specific groups of patients, such as minorities or elderly, were not adequately represented in the studies.
Doran Fink, deputy director of FDA’s OVRR pointed out that a “less than desirable” representation would not warrant restricting vaccines in those groups, as historically, the FDA has never mandated a particular demographic composition to support licensure of a vaccine or EUA.
There was also discussion around considerations for pediatric development and data to support use in pediatric populations. The Pfizer study is the only U.S. study enrolling patients younger than 18 years of age, now testing the vaccine in kids as young as 12 years old.
Fink pointed out the need for safety assessments that include careful evaluation for immune-mediated reactions or enhanced disease to support benefit/risk considerations for pediatric enrollment in clinical trials. In the absence of clinical efficacy data, FDA has proposed using immunobridging to infer effectiveness in children, but the idea was met with some skepticism during the meeting