By: Steve E. Bishop, M.D. on October 13th, 2021
COVID-19 Update 10/13: Moderna and J&J Booster Data
The FDA's Vaccine Advisory Committee is meeting Thursday and Friday to discuss boosters for both Moderna and Johnson & Johnson. Ahead of the meeting, the FDA and the companies released data on their trials.
On this week's update, Dr. Bishop discussed the booster data, including:
- Are the Moderna boosters safe and effective?
- Are the Johnson & Johnson boosters safe and effective?
- What should you expect from the meetings this week?
- What happens next?
Watch the full video below and read on for our recap.
Moderna's Booster Data
Here are the documents we will discuss:
We've got a big treasure trove of information that has come out and I'll be the first to admit, I have not read through all of it. Most of it came out yesterday and each of these items is, 50 or 100 pages long, so, unfortunately, I haven't read through all of them quite yet, but I'm going to post some of the links so you guys can see what we're working through here.
The first one is actually the FDA's briefing document on the Moderna EUA extension request for a booster dose.
So what Moderna did, they are actually requesting authorization for a booster dose six months after the second dose with a half dose compared to the first two-dose series. The first two doses were each a hundred micrograms of the effective material. This one is a 50 microgram dose of the immunogenic material.
What they have presented in this document, it goes through a lot of discussion about the rationale behind why they're requesting this, which is because there are concerns that the protection in terms of hospitalizations, deaths, and severe COVID starts to wane somewhat after six months it appears, based on their information.
They have taken that and then developed this whole rationale about why they're requesting the booster dosing. They ran a couple of small trials with a few hundred patients with this booster dose, this 50 microgram dose, and then they tested the antibody responses and some of the other things to indicate that the booster doses were safe, and then they tracked the adverse events.
The good news is what they did show is that if you give the third dose to people, yes, their antibody responses, and their humoral responses — all the immune system stuff — does improve again and gets a little bit better than where it was before.
And it looks like, in terms of the short-term follow-up, there's good safety information for the third dose. There's no worsening side effect profile compared to the first two doses, except maybe some people were experiencing a little bit more lymph nodes swelling pain at the injection site, a little swelling at the injection site, that sort of thing.
But overall, it seems to be just as safe as the initial two doses, at least in the short term. Now what they did not show in this information is any clinical outcomes data. They did not present any data to the FDA showing an actual change in cases and actual change in hospitalizations or an actual change in the death rate of those who got a booster dose, and I think it's primarily just because the follow-up window is too short.
So while they've made a decent case, and I think that the third booster dose is probably safe and reasonable to get, they really haven't made a strong case that the booster dose is strictly necessary in terms of reducing hospitalizations and fatalities, because they just haven't presented that data.
And the FDA pretty much called that out in their document. They essentially say data shows that the existing Moderna vaccine series continues to provide robust protection against hospitalizations and death.
I think you're going to see a similar response from the FDA to the Moderna booster data as we saw with their response with the Pfizer booster data, which is basically to say, hmm, we're not really sure that this data is compelling enough for us to take a stance one way or another. They will clear it through almost certainly because it appears to be safe and there's no compelling reason to keep it off the market based on the safety data that they have.
They will probably pass it on to the CDCs ACIP committee — we have talked about ACIP a lot, the advisory committee on immunization practice — and then they will be the ones who have to debate the utility and the benefits of using the third dose.
(Editor's Note: The CDC's ACIP is scheduled to meet on Oct. 20 and Oct. 21 to discuss booster data).
I suspect we're going to wind up with the same result as with Pfizer. We'll probably get a general strong recommendation for people 65 and up to get it and then a sort of strongly consider if you're 50 and up, and then for everybody else it's available as an option.
So I bet we'll have the same result from CDC as we had with Pfizer. And then remember the Pfizer decision was controversial. ACIP did not grant a wide recommendation to the Pfizer booster dose and that was changed by the CDC director after the fact.
We'll probably have the exact same outcome this time is my guess, because the data is not overwhelming or compelling for the booster dose in terms of the hardest outcomes, meaning cases, hospitalizations, and fatalities, so I suspect ACIP will say kind of the same as with Pfizer — probably good to do for older people, probably good to do for people who have immune system problems, everybody else it's kind of a toss-up.
And the CDC director will probably do the same thing as last time and make it widely available with a strong recommendation for the elderly and the immunocompromised to go ahead and get the third dose.
Again, I think it's fine. I think that's reasonable based on the data. The data is showing the safety information, and if people choose to do that, I think that's okay. But the data is not overly compelling for the third dose in terms of the outcomes information, and I think that's just the reality right now. I think we all just have to be honest about that the data it's just not that compelling.
It doesn't mean it's bad. It doesn't mean you shouldn't get a booster. It's just not overwhelming in terms of what the data is actually showing us at this point. That's sort of where we are with Moderna. Probably safe to get a third dose. Will probably be available within the next couple of weeks for those who want to get one.
Johnson & Johnson Booster Data
Let's move on to J&J. Here are the documents we will discuss.
Our poor J&J people have been left stranded without any updates on what to do for a long time, and I think this is actually going to provide them with some really good, helpful information on what to do next.
Here is a link to the J&J data for their booster shot information, and I think it's actually fairly compelling.
They did actually show some vaccine efficacy in terms of disease — mild, moderate, and severe, and even asymptomatic disease as well — and COVID-related deaths for a booster dose given two months after the first dose.
Again, it was a small trial, to be sure. That being said, it's still compelling information. It was several thousand patients, so it's not a super tiny trial. It's just not as big as the ones we saw back in the fall for the initial approvals.
A booster dose was given 56 days, or basically two months, after the first dose, and they did see a pretty good, robust improvement in the protection that people got for basically all forms of COVID in terms of mild, moderate, severe, asymptomatic infection went down and COVID related deaths they reported went down.
There was one death in the placebo group and zero deaths in the test group, and that was 14 to 70 days after the second dose. So a little tough to piece out the fatality part there, but pretty significant differences in moderate and severe disease reduction after the second dose — 70% and 100% reduction in those things 14 days after the second dose.
If you follow out to day 71, they showed efficacy around 94% after the second dose for the alpha variant and 63% for the mu variant, which is one of the newer ones that's come around of late.
Safety information, there's again, this is a 117-page document, I have not read through the entire 117 pages, but the safety data seems again pretty similar to the initial safety data and the data that we've already known about J&J, which is that:
- There does seem to be a small non-zero risk of blood clots with the J&J vaccine
- Some issues with thrombocytopenia, which is low platelet count, and
- Guillain-Barre syndrome, which is the nervous system disorder
Some of these things are also common with other vaccines. I don't think that the risks are out of line compared to other common vaccines, like the flu shot and things like that. But just based on my initial sort of looking at the information, the rates of these things are pretty low.
Guillain-Barre syndrome, for instance, they're saying seven to eight cases of this per million doses, and the background incidence of geon bray is maybe four or five per million people out in the world.
I have to look at this a little bit more, but basically, it's still pretty low. These problems are pretty uncommon, but it's non-zero, so it is a risk. Those things are there. I don't think they're inordinate risks. I don't think it makes it, for most people, a vaccine not to take.
That being said, if you've had a history of a blood clot or one of these other disorders, I would continue to steer toward the Moderna or the Pfizer vaccines in those cases, just because there does appear to be some elevated risk there, but this is at least some news for people with the J&J vaccine in terms of knowing what to do next.
J&J: Booster vs. Second Dose
I think the FDA will clear this for a booster — or a second dose, they may actually call it a second dose in the series, rather than a booster — meaning they're going to consider the J&J series to actually be a two-shot series, just like the other two.
That's just based on looking at the data. That's how I would interpret it but that's just me. I would say it's probably a two-shot series, you just got to take the second two months later, versus it being really a booster dose per se, because that's more in line with sort of how we think about like hepatitis B vaccinations or hepatitis A vaccinations or the shingles vaccine.
The second and sometimes even the third dose are multiple months down the line. They're not all done in quick succession, like the mRNA vaccines, where it was three weeks or four weeks after.
In my mind, I would consider, if they approve this, it would be like saying, okay, the vaccine series is really to two doses of the vaccine — one at day zero and one at day 60 basically, which is totally fine.
I think that that's very reasonable, and we'll see. I bet FDA will approve that and they may approve it very broadly for anyone who's already gotten the J&J, or who would otherwise be a candidate for J&J to go ahead and get a second dose if you haven't gotten one, or going forward to get the second dose two months after the first dose.
And I suspect ACIP will probably agree just because the data does actually seem to be fairly compelling from Johnson Johnson.
Now what I have not seen now, what I shared with you guys is actually Johnson & Johnson's briefing document, and I have not seen the FDA's version of the briefing document, which includes their commentary and other information about basically what they're thinking, as we have for the Moderna one today.
So we haven't seen what the FDA staff are thinking about this information just yet, maybe it'll be out tomorrow.
(Editor's Note: The FDA's briefing document was released Wednesday evening after Dr. Bishop's update. Here is a report from CNBC summarizing the information.)
Another thing that's supposed to come out as well that we haven't seen yet is — they're supposed to talk about this week and next week the mixing and matching the vaccines in terms of:
- If you've got J&J is it safe to get Pfizer?
- Or if you got Moderna, is it safe to get Pfizer?
- Or any combination
And they're supposed to be talking about that some, but again, I haven't seen any information on that just yet. So that may be an update for next week.
(Editor's Note: A little bit of information summarizing the mix-and-match data was released shortly after Dr. Bishop's update. Here is a report from NBC News.)
And then, of course, next week, we'll talk about whatever the FDA decided from this week and then probably whatever is going to happen with ACIP.
I believe the ACIP meeting actually may be happening next Wednesday as well, so we may be able to talk about what's going on with that as of next Wednesday too, in terms of what the CDC is actually going to decide.
But my guess is if you're looking for a Moderna booster shot, they will probably be available the week after next, so probably the last week of October. This is my guess based on the information we see here and how things went about with the Pfizer vaccine. So probably if you want to get a booster of Moderna, my guess is it'll be available the last week of October.
If you want a booster of J&J? Probably the same. Probably also available last week of October. That's my speculation based on the information and just looking through it here today, because there doesn't seem to be any major safety concerns that would cause the FDA or the CDC to take great pause in offering it.
That's some good news. Good news for everybody who is looking for a booster vaccine. Good news definitely and especially for our older folks 65 and up or anybody who's at heightened risk in that 50 and up crowd, you certainly should probably strongly consider getting booster doses or the second dose of J&J if you had the J&J the first time around.
And I might recommend actually, based on, we'll see what the FDA says in their commentary, but it probably would make very good sense for anybody who got J&J to go ahead and get the second dose at this point and not really consider it a booster per se, but as the second dose in the series, but we'll see what FDA has to say about it tomorrow and Friday.
COVID + Flu + Shingles Vaccine Timing
"I got the flu and a COVID booster Saturday. How long should I wait for the shingles shots?"
I would wait at least a week, maybe two. There's no specific contraindication or any medical safety reason that you have to wait. I just tell people to wait because the COVID booster can make you feel a little crummy and the shingles vaccine can make you feel pretty crummy, too, especially the second dose.
I've been telling people to wait a week or two after your COVID booster to get your shingles vaccine. Or vice versa if you just got shingles vaccine, wait a week or two to get your COVID booster. Just so you're not slammed with both of those at the same time. You're going to feel pretty crummy if you do them close together, so wait a week, maybe two weeks, and then go ahead and get your shingles vaccine. That's been my advice to most folks.
So good question, which kind of brings up something I was talking about with a colleague a little while ago. I'll be really interested to see, I think Moderna will eventually come out with data on a combo COVID + flu vaccine, which I think will be fascinating and we'll make some of this stuff a little bit simpler. I'll be really interested to see how that works, simplify things a little bit.
Waiting Period After a Booster
"Once you get a booster, is it the same waiting period for it to take full effect? I know for the original ones, it was about two weeks after you finished that the vaccine will be fully rocking."
Yes, that's the general rule of thumb for any vaccine. It takes about two weeks for it to really kick in. That's how long it takes for what's called the adaptive immune system to actually go through its whole process of recognizing an antigen, using the B cells to process it, and then to go through a whole series of antibody development sequences.
So when antibodies develop, there's a whole process there. We start developing IgM antibodies at first, and those are like the temporary ones that aren't as good, and then over time they get better and better at detecting and eliminating the pathogen and they switch classes.
There's actually a whole big group of classes of different antibodies, there's IgM, there's IgD, IgE, IgA and there are subclasses of all those as well. What you want is the IgGs, and those take about two weeks to show up.
There's a whole process there, and you have some memory from the first two types, so it might be a little bit faster, but our rule of thumb generally is just to say two weeks. It's simpler. It's an easy rule of thumb to follow. It probably is a little shorter if you really want to get technical about it, but two weeks is a good rule of thumb.
New COVID Treatment Pill from Merck
"Thoughts on the newest COVID treatment pill from Merck?"
Yeah, it's interesting. I am not yet totally convinced about that drug. Molnupiravir is the name of it, a complicated name. I suspect they'll come up with something much easier to say for the marketing of it.
They did a small trial of it. It was only a few hundred patients. It does appear to work in terms of a pretty dramatic reduction in fatalities and hospitalizations. It does appear to work, which is good, so I think probably for patients that are very sick or very high risk, and probably those who are older, it probably makes sense to use it.
My worry, frankly, is the side effect profile seemed to be pretty profound. There were like 30% of people that had a side effect from the drug. Now I haven't seen all the full data yet. I don't know if that side effect was a mild headache or if it was something worse than that.
The other thing that worries me a little bit is the way that the drug works, and I just need to parse into that a little bit more.
It works by incorporating an abnormal nucleotide, or basically, it uses an abnormal RNA molecule building block to basically break the viral replication mechanism, which is fine. The problem is, what concerns me, is does that abnormal building block only get incorporated and used by the viral RNA polymerase?
So an RNA polymerase is the little machinery that actually makes the copies and transcribes and copies out that the viral RNA. Humans have their own RNA polymerases to make RNA. My concern, and the only thing I'm worried about, is does that abnormal building block — which is what the drug is — does that get used also by the human RNA polymerase?
If so, that's a big problem potentially, because then we've got a human RNA polymerase using this abnormal nucleotide, which is designed to cause mutations. That's what its job is, to cause mutations in the RNA that then cause it to break and not work. If it just works on the virus, that's awesome. If it also is picked up by the human RNA polymerase, that may be a real concern in terms of cancer risk and things like that.
So I'm a little worried about that. I need to see more information before I can come to a conclusion on that. And so I think Merck is going to have to really release a lot of data on that to convince folks that that's a safe and reasonable drug to use, especially in younger people.
Now folks in their 70s and their 80s and things like that, where there's maybe not a super-long, multi-decade concern over the risk of cancer, it maybe is not such a big deal.
But if we're talking about 30 or 40 or 50-year-olds, giving them a drug that we don't really fully understand the implications of that mechanism that may be a problem. So we're going to have to see a little bit more information about that.
Flu Season Update
"How is the flu season shaping up so far?"
Yeah, it started early. It started early, and we've seen a slow trickle of cases. It seems to be out there. It's not zero. It's not overwhelming, but it is there more than last year for certain.
I haven't looked at all the data coming out of the VDH on that, but it definitely is being reported in most places around the area here. We see a couple of cases a week here at our practice, so we will see how that goes. It looks like VDH is reporting what's called "regional influenza activity," so that's consistent with what I'm saying. It's out there, but it's not widespread, so we'll see how things go the next few weeks.
Expected Side Effects from J&J Booster?
"Does the data shows side effects from the booster for J&J? I know some people experienced more side effects with the second shot from the other two vaccines. Just wondering if we need to expect that from the J&J booster?"
Yeah, a good question. The side effect profile for the second dose seems to be, from what I'm seeing initially here, pretty similar to the first dose, which is to say not super significant in terms of the acute side effects. It seems to be similar to the others. Maybe some muscle aches, body aches, fever, chills, that sort of thing.
The thing that is a little bit unique for the J&J is the risk of blood clots and things like that. It's the same warnings for the booster as for the first one, so I think most people probably don't need to be too worried about that.
I think that people who have a history of a blood clot, or perhaps if you're in one of the categories that had the recommendation for J&J been a little bit softened in terms of if you're a younger woman, maybe you should consider getting one of the other ones because of the blood clot risk.
I think that those caveats all still apply for the J&J vaccine, but otherwise, the side effect profile seems to be fairly similar to the first dose. I haven't parsed through it all in great detail, but I didn't see anything in my initial overview that really stood out in that way so, yeah, good question.
When is the next update?
We will go ahead and wrap things up. Thank you for reading, and we will see you next Wednesday, October 20, at 1:00 pm on our Facebook page. For those without Facebook, we will post our written recap on Thursday morning.
We will have an update on whatever the FDA decided in terms of these things, and then hopefully we will have imminent decisions, either that day or the next, from the ACIP committee and CDC in terms of what they are actually going to recommend and approve.