Sandra Fryhofer, MD, on the two fully licensed COVID vaccines

Watch the AMA's COVID-19 Update, with insights from AMA leaders and experts about the pandemic.

In today’s COVID-19 Update, AMA Chief Experience Officer Todd Unger dives into new developments from ACIP's emergency meeting on Feb. 4 with Sandra Fryhofer, MD, AMA’s liaison to the Advisory Committee on Immunization Practices (ACIP) and a member of ACIP’s COVID-19 Vaccine Workgroup. Also covering expanded intervals between vaccine doses and not needing to delay vaccine or booster shots after receiving certain COVID treatments.

Learn more at the AMA COVID-19 resource center.

Speaker

• Sandra Fryhofer, MD, physician, chair-elect, AMA Board of Trustees and AMA Liaison to ACIP

Unger: Hello, this is the American Medical Association's COVID-19 Update video and podcast. Today we're discussing the latest news on COVID vaccines from the CDC's Advisory Committee on Immunization Practices, or ACIP.

I'm joined today by Dr. Sandra Fryhofer, AMA's liaison to ACIP and a member of ACIP's COVID-19 vaccine workgroup. Dr. Fryhofer is also the chair-elect of the AMA Board of Trustees. I'm Todd Unger, AMA's chief experience officer in Chicago. Dr. Fryhofer, welcome back. ACIP had an emergency meeting on February 4. Let's talk about what triggered the emergent nature of this particular meeting.

Dr. Fryhofer: Well, it was the announcement that FDA had finally fully licensed Moderna's COVID vaccine. Moderna's mRNA COVID vaccine now has full FDA approval for those 18 and older. It also has a new name, Spikevax. ACIP called this emergency meeting. We reviewed the data, and ACIP voted unanimously to recommend it. Moderna's FDA approval came as a priority review, meaning that the FDA took action within six months, rather than the standard 10 months, but it seemed like it took forever.

January 31 turned out to be a really big day in the fight against COVID. Moderna's vaccine, of course, was approved that day. But that same day, Pfizer submitted data to FDA for its two-dose, baby sized three microgram series for children age six months up to five. And Maryland-based company Novavax submitted data for its protein-based COVID vaccine, which uses nanoparticle technology and contains a proprietary adjuvant, Matrix-M.

Unger: Wow, what a difference a year makes. We now have two fully-licensed COVID vaccines. Will you tell us more about that?

Dr. Fryhofer: Yeah. So first there was Pfizer, now called Comernity, licensed by FDA on August 23, 2021 for those 16 and older. And now Moderna's fully licensed as Spikevax but it's only an option for those 18 and older. Pfizer's still the only game in town for those under age 18. An adult 30-microgram dose of Pfizer is now fully licensed for 16- and 17-year-olds.

The EUA authorizations are still in place for younger children, an adult 30-microgram dose for those 12 to 15 and a 10-microgram kiddie dose version for those age five to 11. The thumbs up for Spikevax was the only ACIP vote at our last meeting. But CDC also announced several EUIs, emergency use indications, mainly for moderately to severely immunocompromised patients.

Unger: Well, that's a new term. I've heard of EUAs and I know what that means. What is EUI, emergency use indication? What's that mean?

Dr. Fryhofer: So FDA issues BLAs, biologic license applications, which means full FDA licensing and approval. As you said, FDA can also issue EUAs, emergency use authorizations, and they've done this so many times during this pandemic. But under the Pandemic and All-Hazards Preparedness Reauthorization Act, CDC is allowed to issue these EUIs, emergency use indications.

CDC has done this twice in the past but both times were during the anthrax attacks in 2001, so more than 20 years ago, for use of Cipro and for use of doxycyline in children for anthrax post-exposure prophylaxis. Emergency use indications apply to emergency use of FDA approved medical products.

These emergency indications can be different from what's in the FDA approved package insert. There's a lot of legalese here and CDC representatives at our ACIP meeting were very clear. These EUIs are being made in close consultation with FDA. The current EUIs only apply to FDA approved Spikevax, made by Moderna for those 18 and older, and for Pfizer's FDA approved Comernity and will apply to those 12 and older.

Unger: That is a lot to take in. When we think about these EUIs, tell me again, what do they exactly apply to?

Dr. Fryhofer: So for now, the EUI includes four updates for people with moderate to severely immunocompromising conditions. For immunocompromised patients who have completed a three-dose mRNA vaccine primary series, their fourth dose, which is their mRNA booster, should come sooner, not later. So they should get their booster now at three months, rather than waiting five. But the boosters only apply to those 12 and older.

For immunocompromised patients who received a Janssen primary series of one Janssen dose, an additional COVID vaccine dose, which should be an mRNA vaccine, is now recommended at least one month later. They then need a boost dose at least two months later but this can be with any age-authorized COVID vaccine. But again, mRNA vaccines are preferred. So the two-month boost interval for Janssen remains the same.

Revised guidance also includes re-vaccination for some, for recipients of hematopoietic cell transplants and CAR T-cell therapy, and other B-cell depleting therapies who received vaccine doses prior to or during their treatment. Consideration for re-vaccination has also been extended to those who were previously vaccinated while receiving chemotherapy or radiation therapy.

The new guidance also gives physicians who care for moderately or severely immunocompromised patients some flexibility. The EUI allows for administering vaccines outside FDA and CDC dosing intervals based on the physician's clinical judgment. And this could help target vaccine administration to times at which immune response is more likely to be successful.

Unger: Well, as you're talking, I'm thinking about the chart that lays all these different folks out and when to do what. Is there any other discussion coming about changing vaccine dose intervals for other groups?

Dr. Fryhofer: Well, there was a fascinating review of international data regarding vaccine intervals. In the U.S., COVID vaccine intervals for a primary series were specified and authorized under EUA by FDA with strict protocols. For Pfizer, three weeks between doses. For Moderna, doses should be spaced four weeks apart.

But this didn't happen in other countries. They were not limited to these specific intervals. Internationally, extended intervals started out of necessity as a way of best using valuable vaccine resources. But studies now show, the longer interval is a win-win for patients. Review of international data reveals extending the interval between doses has double benefits.

The longer interval increases vaccine effectiveness based on data from the U.K. This improved vaccine effectiveness interval benefit seems to level out at eight weeks. An extended interval also lowers rate of myocarditis based on data out of Canada and other countries. These studies were discussed in our COVID vaccine work group. Our work group proceedings were revealed at the ACIP meeting. Our work group was supportive of extending the vaccine interval between doses to at least eight weeks based on the new data.

There's also accumulating international evidence that risk of myocarditis is higher after Moderna as compared to Pfizer vaccines, with the highest myocarditis risk in young males after the second dose. But remember, Moderna vaccination has seemed to be more durable. A CDC recommended change in the interval between doses would probably come as an EUA, emergency use indication. It may not require an ACIP vote but this has not happened yet.

Unger: Well, just turning to a slightly different topic and one that's on a lot of people's minds. Will you tell us more about where we stand with vaccines for children younger than five?

Dr. Fryhofer: Well, as I said earlier, Pfizer has now submitted data for their two-dose baby sized three microgram series for children aged six months up to five years. Now, this dose is 1/10th of the dose for adults. You may recall Pfizer's earlier press announcement that two doses failed to meet criteria for a satisfactory immune response in children age two through age four. But it did mount an adequate immune response and little ones six months up to two- years-old.

Research continues on whether three doses will be more effective than two doses for the two, three and four-year-olds but those data will not be available until late March, probably. Meanwhile, the FDA, the data's been submitted, FDA will start its review of the data. I know many parents are anxious to have a vaccine for these younger children. And even though many young children tend to do well combating the virus, some get very ill.

Unger: Geez, this is a lot to take in. It's just another example of how we are really learning and adapting in real time to this. Dr. Fryhofer, any additional thoughts before we close?

Dr. Fryhofer: Well, there's one more thing I want to tell you about, which is new. You no longer have to delay COVID vaccination or boosters after monoclonal antibodies or convalescent plasma. This change will help more people become up-to-date on vaccinations more quickly. However, administration of the antibody cocktail, Evusheld, should be deferred for at least two weeks after vaccination as per the product EUA.

The Omicron variant is dominant in the U.S. And it now seems that the Omicron we know, which is B.1.1.529, the BA.1 version, has a sister variant virus, BA.2. News reports say BA.2 is now the dominant variant in India, Denmark and several other countries, from South America to the Philippines, to Sweden and the United Kingdom. News reports also suggest it may be more transmissible than BA.1. But fortunately so far, Omicron's BA.2 sister does not seem to cause more severe disease.

There's also some important data that was presented at the February 4 ACIP meeting. In November, unvaccinated adults 18 and older were four times more likely to test positive for COVID, and 15 times more likely to die from COVID compared to those that received a full primary series. Compared to those both fully vaccinated and boosted, unvaccinated people were 13 times more likely to test positive, and 68 times more likely to die from COVID.

More than 900,000 people in the U.S. have already died from COVID since the pandemic began. And even during the Omicron surge, vaccination and boosting continue to protect against severe illness and hospitalization. As of January 25, 26.1% of people 18 and older were still not fully vaccinated. They need to be. The message is clear. Get vaccinated and get boosted.

Unger:

That message is clear and those numbers are very clear and compelling. Dr. Fryhofer, thanks so much for being here and sharing the latest updates. That's it for today's COVID-19 video and podcast. We'll be back with another segment soon. In the meantime, for resources on COVID-19, visit ama-assn.org/COVID-19. Thanks for joining us today and please take care.

Disclaimer: The viewpoints expressed in this video are those of the participants and/or do not necessarily reflect the views and policies of the AMA.