Source : 'The Pink Sheet'
Moderna’s COVID-19 vaccine got a more solid ‘yes’ vote than Pfizer/BioNTech’s, but committee chair cautions against drawing any comparisons between the products from the different tallies. Last-minute bickering over FDA’s phrasing of voting question complicated meeting but resulted in minimal harm.
Moderna, Inc. ’s COVID-19 vaccine got a more resoundingly positive vote from an FDA advisory panel than Pfizer Inc. and BioNTech SE’s candidate achieved the week before, but the difference is unlikely to have much real-world impact.
On 17 December, the US Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee voted 20-0 with 1 abstention that the benefits of Moderna’s vaccine outweighs its risk for use in individuals 18 years of age and older. The agency issued a statement later the same evening saying that it would rapidly work toward finalizing and implementing an emergency use authorization.
Committee Chair Arnold Monto quickly cautioned against reading too much into the vote differences – four panelist voted against the Pfizer vaccine on 10 December and one panelist abstained. While the two panels were not identical, all the committee members who voted no or abstained were on both panels. ("US FDAs Vaccine Advisory Committee Roster Tweaked For Moderna Review" "Pink Sheet" )
“I don’t think that anyone should interpret the difference in the vote being one way or another comparing the two vaccines that we have considered,” Onto said, adding that there is “clear benefit” that outweighs the risks with both vaccines.
Monto noted a primary reason for the nay votes on Pfizer’s vaccine was concern about including 16- and 17-year-olds in the authorized population for that vaccine due to more limited trial data in this population. This was the reason for two “no” votes and one abstention. ("PfizerBioNTech COVID19 Vaccines Positive Advisory Committee Complicated By Pediatric Issues" "Pink Sheet" )
These three panelists, Archana Chatterjee, dean of the Chicago Medical School and VP of Medical Affairs at Rosalind Franklin University; David Kim, director of the vaccine division in the Health and Human Services Office of the Assistant Secretary for Health Infectious Disease and HIV/AIDS Policy Office; and H. Cody Meissner, director of pediatric infectious diseases at Tufts Medical Center, all voted in favor of Moderna’s vaccine, which is not seeking authorization for 16- and 17-year-olds.
But two other panelists voted no on Pfizer’s vaccine for different reasons. A. Oveta Fuller, University of Michigan, voted no because of a preference to have the vaccine rollout done through the expanded access pathway not an EUA, and Michael Kurilla, director of the Division of Clinical Innovation at the National Institutes of Health’s National Center for Advancing Translation Sciences, voted no out of concern the question didn’t clearly distinguish that the vote was for an EUA versus a full biologics license application (BLA).
Fuller voted yes for Moderna’s vaccine, but her explanation of her vote indicated her opinion hadn’t shifted since Pfizer’s meeting, just that Moderna’s got the perk of being up second.
“I did not think an EUA was the way to go. But since the train has left the station, I appreciate that Moderna has given us a very transparent and thorough study that even from the beginning seemed to be very well organized with getting people with underlying conditions, with monitoring activity throughout the study, with even including the serology and nasal swabs, which are not completely analyzed at the moment, but which have great potential to look at important aspects. And then lastly, the care for the study participants throughout including a plan for monitoring adverse effects, as well as what to do with people who now may want to move in from the placebo. So I appreciate the way that they've conducted a much more transparent and clean study,” she said.
Kurilla abstained this time, but for a very similar reason to his no vote on Pfizer’s vaccine.
“I abstained because I'm very uncomfortable with the language. I think in the in the midst of a pandemic and with limited vaccine supply available a blanket statement for individuals 18 years and older is just too broad,” said Kurilla. “I'm not convinced that for all of those age groups, the benefits do actually outweigh the risks. And I would prefer to see it more targeted towards people at high risk of serious and life-threatening COVID disease. And they have that information and we understand to a certain extent those high-risk groups so it could be targeted.”
Like Fuller, Kurilla said he would have preferred using the expanded access program over an EUA to get more vaccine to Americans prior to a full BLA, because he believes expanded access provides greater ability to continue to collect data on the vaccine. ("COVID Vaccines Is Expanded Access A Better Option Than Emergency Use Authorization" "Pink Sheet" )
Figuring out how to fill in the missing knowledge gaps like vaccine durability, long-term safety and any benefits on transmission is a challenge post-EUA as sponsors feel they have an ethical obligation to vaccinate the placebo participants.("PlaceboUnblinding Should Be Uniform Across COVID Vaccine Trials Advisory Committee Says" "Pink Sheet" )
Kurilla pushed for FDA to change the wording of the voting question, saying that while the advisory committee has been discussing granting the vaccine an EUA not a BLA, “the question really doesn’t reflect that. It could easily be seen as full approval.”
“There’s quite a bit of confusion,” among the general public, the media and even among medical professional about whether FDA is currently reviewing vaccines for EUAs or full approvals, Kurilla said.
“I think that the distinction between an EUA product which is still an investigational product, and the full approval of product with a BLA is a distinction we need to maintain. And I think we're losing that simply by looking at this as an age related anyone over the 18 years of age and an older. It doesn't strike me as really addressing the emergency which is severe and serious, life-threatening COVID disease in specific populations,” Kurilla said. “So I have a lot of problems, because this could be interpreted as us actually recommending full approval of the vaccine. And in the minds of the general public that may happen and it may preclude not only adequate evaluation of this vaccine, but other future ongoing COVID vaccines.”
This comment led to about 20 minutes of debate as to whether FDA should modify the voting question to specifically include language referencing the term EUA.
But most VRBPAC members were fine with the question as written and FDA declined to budge.
“I don’t want people to interpret this the same way they would a licensed vaccine,” Meissner said, but then added he was fully comfortable with the wording if the majority of committee members was.
One panelist worried the focus on the wording would confuse the public.
After advising the FDA, “the second reason we’re here is to inspire confidence in the public that we’ve looked carefully at the data,” said Eric Rubin, editor-in-chief of the New England Journal of Medicine. “When we worry about the details of the wording, I’m not sure we’re helping people understand what almost certainly will be … a strong vote in favor.”
By Sarah Karlin-Smith