“I’ve seen nothing like this. I guess the thing that’s most upsetting to me is normally when you get something from the FDA when we have these meetings, you usually get it a few days before you meet. You usually get a couple of hundred pages.
“Here on the other hand, normally you get the EUA [Emergency Use Authorization] submission from the company, which is 85 to 100 pages long, and then you get the FDA’s review of all those data. It’s a very thorough review. Not here though. Here, it was 22 pages from the FDA, which included a half-page on Pfizer’s data and a half-page on Moderna’s data.”
The question vaccine advisors are always asked to consider in the end is whether the benefits outweigh the risks — even if the risks are generally small and sometimes unknown, Offit said. “I didn’t see the benefits.”
“I think this was something that was desired by the Biden administration,” he added.
“I could be wrong but the other thing that was odd about this meeting was that we’re an advisory committee, we’re being asked for our advice,” Offit said. “So normally what happens is that they just present the data. Here’s the data. What’s your advice? And people can ignore our advice.”
Offit said all COVID-19 vaccines are based on the original Wuhan strain before it “mutated and left China,” and now that BA.4 and BA.5 represent a little more than half of the circulating strands in this country.
It’s reasonable the FDA would consider trying to broaden immunity by including omicron or omicron subvariants in a bivalent vaccine, he said. But “both Moderna and Pfizer presented data during the June 28 meeting and it was not compelling.”
“They did the studies the right way. So, they took people who had already received three doses of the ancestral strain and then gotten a fourth dose with the ancestral strain and compared that to three doses of the ancestral strain, plus the fourth dose of the bivalent strain which contains the omicron mRNA vaccine [BA.1] as well as the ancestral vaccine. That’s the right way to do the study.
“Then … they looked at virus-specific neutralizing antibodies against omicron and … found … when you got the omicron boost you had a 1.75-fold increase in neutralizing antibodies against omicron.
“Well, the question is, what does that mean? What does that number mean, and the answer is I think while statistically significant, I don’t think that’s a clinically significant difference.
“The reason I say that is because if you look at the original vaccines when they were authorized back in mid-December 2020, there was a two-fold difference between Moderna and Pfizer regarding neutralizing antibodies. Moderna had a two-fold increase in neutralizing antibodies, but it did not translate into a clinically significant difference in terms of protection against severe disease, which is the goal of this vaccine.”
Offit said his second concern was whether COVID-19 vaccines protect again BA.4 and BA.5 subvariants once Omicron is gone.
“Now both companies interestingly presented data after a fourth dose that showed you what the neutralizing antibody titer was to BA.4/BA.5, but they didn’t show you what the neutralizing antibody titer to BA.4/BA.5 was if your fourth dose was the ancestral strain,” Offit said. “They never showed those data.”
“That’s the obvious thing to do because that’s why you have control groups for your experiment, and I just found it odd that neither presented,” he added. “That bothered me.”
FDA Burden of Proof for COVID-19 Vaccines ‘Is Going Down’“There are potentially billions of dollars at stake to transform a vaccine from the ancestral strain to a new bivalent strain including these Omicron-specific boosters, without clear and compelling evidence that it’s actually going to improve the outcome we care about most which is protection against severe disease,” ZDoggMD told Offit. “And yet it seems like the burden of proof for FDA seems to be going down and down and down instead of being at a level that you’re comfortable with.”
Offit pointed out that a reformulated booster is a new product and it surprised him so many were willing to go forward with such “uncomfortably scant evidence of benefit.”
“No one would have predicted myocarditis associated with mRNA vaccines. I don’t think anybody would have predicted this clotting problem so-called thrombosis with thrombocytopenia syndrome. So humble yourself. … If you clearly have evidence of benefit, great, but if you clearly don’t have evidence of benefit then say no.”