Is the 3rd Moderna vaccine/ booster an emergency for people who have already had 2 doses?
When do we move past EUA and use traditional (BLA) approval?
When it comes to drugs, the FDA has the option of granting accelerated approval. This pathway allows drug products to come to the US market without proving they help people live longer or better, but solely based on augmenting a biomarker thought “reasonably likely” to predict one of those two things.
Accelerated approval is limited to conditions which have “unmet medical need.” But what precisely is an “unmet medical need”? Previously, led by Eric Lu, we found that academics use the term unmet medical need indiscriminately in cancer medicine. Yes, the term referred to conditions that were rare, dire, and had few treatment options, but at other times, the term was used to describe situations that were common, indolent, and had a plethora of options. How can that be an unmet need?
Even “reasonably likely” has been expanded. Recently amyloid levels in the brain have been used to support accelerated approval for Alzheimer’s disease, despite prior FDA guidance saying this endpoint was not reasonably likely to predict improvements in function. The drug in question was aducanumab—it will cost society billions, but is also one where no one has any idea if patients live longer or better by using it.
In short, accelerated approval has been abused.
Now, let’s turn to the COVID19 pandemic. When it comes to granting permission to use vaccine products, the FDA has two options—the traditional approval process, and the Emergency Use Authorization. Here is how the EUA is defined:
FDA may authorize unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when certain criteria are met, including there are no adequate, approved, and available alternatives.
[CRBN stands for chemical, biological, radiological, and nuclear]
Furthermore, FDA notes:
On February 4, 2020, the HHS Secretary determined that there is a public health emergency that has a significant potential to affect national security or the health and security of United States citizens living abroad, and that involves the virus that causes COVID-19.
All that sounds good to me, and I was a vocal supporter of the original vaccine EUAs. Moreover, in these trials the sponsor showed the product reduced symptomatic disease—a higher bar for evidence than showing merely improvement antibody titers. Yet, currently, the FDA is advancing the EUA authority. Specifically, this pathway was used for the Pfizer booster, and is poised, after the advisory vote, to be used for the Moderna booster.
This raises the question: In a world where getting the first dose to all eligible adults remains far from a reality (PS: we must vaccinate all adults who desire vaccination, globally ASAP), is it justified to claim that a 50 microgram booster of Moderna vaccine is warranted for a 24 year old health care worker, who already had two 100 microgram doses of Moderna, under the auspices of an EUA?
COVID19 remains an emergency for the unvaccinated, but is COVID19 an emergency among the vaccinated? Particularly among young people who have already gotten 2 doses of Moderna (the vaccine dose and schedule that continues to retain the highest vaccine effectiveness numbers in real world studies against severe disease)?
Obviously, the same regulatory trade-off is present as with accelerated approval. EUA allows the sponsor to bring the product to market with less certainty about benefits and more uncertainty about harms. In this case, we know with certainty is that a third dose improves antibody titers. But we don’t know about slowing transmission. We don’t know about reducing severe disease.
My last question is this: When will EUA authority end? Will annual boosters attempt to come to market via EUA?
The core question of drug and vaccine products remain: If drugs and vaccines make people live longer or better with side effects that do not offset gains—their approval is a given. I celebrate those products. Moreover, that is a logically defensible bar.
But if we permit products with less and less evidence to come to the market what justifies that? I believe exigent times and desperate circumstances do. The original vaccine series clearly was an emergency. The Moderna booster for a 20 year old health care worker (which is included as the topic of current EUA) pushes EUAs to the limit.