FDA authorizes frequent Covid-19 boosters for the immunocompromised, Spring boosters for ages ≥65, moves to bivalent-only regimens.

Also, an Inside Medicine scoop on the potential for additional boosters during pregnancy.

The FDA has announced major changes in its Covid-19 booster strategy.

Here are four takeaways, my analysis, and some new quotes from emails I just exchanged with Dr. Peter Marks, the Director of the FDA’s Center for Biologics Evaluation and Research, which includes a scoop on some potentially breaking news for the future regarding boosters during pregnancy:

Four key takeaways:

1. An additional bivalent booster (2nd doses) is now authorized for people ages ≥65 who are at least 4 months out from their first bivalent dose.

2. People with immune compromise may now be boosted as frequently as every 2 months. This is a major change which I’ll discuss in depth below. (There are some caveats for children under age 5, depending on individual vaccine history.)

3. The primary series (for the unvaccinated) will now be the bivalent vaccine. A single dose of the bivalent vaccine will now suffice for most people, though for children under age 6, the old multi-dose primary series strategy will remain in place (i.e., two doses for Moderna or three doses of Pfizer-BioNTech).

4. No change regarding pregnancy and additional boosters. This was not mentioned in the FDA announcement. However, I learned today that the FDA will consider authorizing additional booster doses during pregnancy and that’s news I wanted to share and highlight with you right away.

Analysis:

Points 1-2: As I wrote recently, repeat doses for the immunocompromised population makes sense, as well as older people. So this is good news. I’ll add that I’ve been engaged in research with epidemiologists in Israel (Clalit Health Service, the largest healthcare providing organization there). Together, we have been studying this question closely. We believe that for severely immunocompromised people (e.g., patient with cancer on chemotherapy, organ transplant recipients), a routine every-6-month booster cadence likely makes sense, and possibly more often (The same is true for older people too, though the array of risk makes it a bit more situational. The benefit for younger people with milder immune compromise is far less clear.)

Our data do point towards even more frequently boosting severely immunocompromised and even people in oldest age groups with intact immune systems (certainly people over age 80, and likely worth it for anyone over age 60)—which is why I was quoted in the Wall Street Journal about this point. In fact, we preliminarily looked at a 3-month cadence for the highest-risk groups and see signs that such a strategy might be worth it.

So where does the FDA’s new 2-month booster cadence for the immunocompromised come from?

I spoke to Dr. Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research via email today. He told me that, “the data for the immunocompromised are varied” and that “references are noted in our review memo, which will be posted in the next day or so.” He added that the FDA was “asked to provide maximum flexibility, and the benefit risk showed reasonably low risk to the approach with the 2 month interval.”

This is important to untangle.

Basically, Marks is saying that the benefits of a very frequent booster cadence for the immunocompromised are great enough that it would take unexpectedly higher new rates of adverse side effects to require any dialing back. While I’d say we are in uncharted territory here, the rationale is sensical, especially because this small population does not build a strong enough immune response to the vaccines to begin with—which is why we’ve needed to boost them more and why side effects have been lower in this group.

The FDA is probably also recognizing that every situation is unique, and they’re probably going to be unable to address them all. So, they’re basically deciding to stay out of it, with regard to this high-risk, highly variable population. We see this with many products—but not for ones under emergency use authorization. This feels a bit more like the flexibility we see with fully-approved FDA medicine and vaccines (which these vaccine are not). So this is newsy.

That said, I’d like to see safety data for any vaccine cadence that exceeds what we’ve already done (which has been 4-6 months for certain groups at certain times). In the present environment, it would not be hard to do this, and perhaps we’ll see data on that in the FDA’s memo. In sum, while I am convinced of the short-term benefit of frequently boosting the severely immunocompromised, I would like to be certain that all of the risks are accounted for.

Point 3: The move to using the bivalent vaccine for the primary series makes sense to me. The Wuhan virus is not around, so it makes sense to show less of it to our immune system. In fact, the best move would be to eliminate Wuhan components from the vaccine, and I suspect fall 2023 boosters will go in that direction. The reason for this is that the effect of Omicron-only boosts are likely to be stronger (and possibly longer lasting), and would be less likely to cause “imprinting,” which is when our immune system becomes so primed for one version of the virus (Wuhan) that it is actually somewhat less prepared for another (Omicron).

The other reason a move to using only bivalent vaccines makes sense is simplicity. We don’t want multiple vaccines floating around if the effectiveness is not drastically different, vaccine to vaccine. I do expect a fall booster may be monovalent Omicron, and the idea of three vaccines in use seems needlessly complicated.

Some news on boosters and pregnancy?

Point 4 (a scoop?): There was no news on additional boosters during pregnancy in today’s FDA announcement. In my view, not authorizing an additional dose during pregnancy is a missed opportunity to protect the maternal-fetal duo. Pregnancy is a higher risk period and infancy is an extremely high-risk period. As I’ve written, we should allow this—and recently, the WHO agreed.

However, I asked Dr. Marks about any FDA movement on this, and he expressed interest in the idea. “The issue of potentially boosting during pregnancy is a good one to raise and one that we will consider further as things evolve,” he told Inside Medicine. “CDC may also decide to take this up.”

So, did we break a little news here on additional doses possibly being authorized during pregnancy? Maybe!

What are your comments and questions?