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Xavier Becerra, HHS [00:00:10]
This week is going to be pretty eventful for the state of Idaho and I hope that the courage that you and your colleagues on the council display, the courage that providers display, and certainly the courage that patients display will drive so much of what happens moving forward in the future in this country.
President Biden is fully behind what you’re doing. I couldn’t be more emphatic to say to you that the president has said to us, at the Department Health and Human Services, pull out all the stops to make sure that you are giving every American the access to the care that they need, regardless of what that might be, including abortion care. And so that’s what we’re going to do.
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Xavier Becerra, HHS [00:37:21]
The final point again here in Idaho. I don’t know if any of you got the word I got the word because my folks in DC were in touch with me.
There’s apparently a leak. Or report by a newspaper saying what the decision by the Supreme Court was going to be on this decision impacting Idaho and its treatment of emergency medical services.
We don’t– nothing– no one’s confirmed it, so I’m not going to go out there and say what it was.
But what I will say is this. When these decisions by politicians start impacting the way doctors practice or the way patients can exercise reaching out for the care they need, there are consequences.
And We’re probably this week, maybe even today, going to get the decision on whether or not emergency care is still out there for every American.
Certainly the issue that came up in this particular case, and we’re the ones that sued the state of Ohio for denying a woman access to the emergency care that she needed.
But if anyone believes that in losing Roe versus Wade, in the Dobbs decision, that only abortion care was impacted, then now you’re beginning to see whether it’s in vitro fertilization or emergency care, all these decisions.
Politicians don’t make them while they’re voting about whether or not your life is at risk or not. It’s the doctors do and if they have they’re not sure what they can do because they may get prosecuted in court, and find the consequences of not having done the care, as perhaps being labeled as malpractice and then also being in court it puts a really big burden on our doctors throughout the country.
But here’s where I think we have to recognize how important this is.
As much as President Biden has given us the tools to protect your privacy so your information as a patient your information as a provider we’re doing everything we can to make sure that is not shared outside of that relationship.
So some prosecutor in some other state can’t go out there and say, I want that information about what you, what the procedure you got, medical procedure you got in a particular state.
We’re doing everything we can to make sure that we continue to provide access to, for example, contraception care.
There is now over the counter medication that you can take for contraception. We’re going to fight to make sure that it’s protected.
We’re fighting to make sure that medication abortion is protected. And mifepristone, which a couple weeks ago the court decided, it’s going to continue to stay on the market. It’s been safe for over 20 years.
No reason why we should be taking that off. We’re going to continue to do everything we can.
But there’s nothing that replaced the protection we had under Roe versus Wade. And so I hope the more you all are willing to speak and tell your personal stories, maybe people will start to get it, that this has consequences for more than just that woman who needs abortion care.
It has consequences that go well beyond. And we should be trying to include everyone in getting access to care, not exclude people because of our politics.
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Xavier Becerra, HHS [00:42:00]
So I do think it’s important to wait and not speculate much, but I’ll simply repeat what we’ve always said and that is anyone America who is at risk of dying, or losing their health, their health status and needs to go to an emergency room, should be able to go to an emergency room.
That’s always been our position. Whether the care that a professional, a medical professional says you need to stabilize your health or to save your life is an abortion or not, bottom line is none of us wants to be denied access to an emergency room when we need it.
And that’s where we believe the federal law, EMTALA, the emergency medical treatment law, protects all of us in getting medical treatment that we need and why I continue to say when Roe versus Wade was struck down it impacted more than just abortion care. It impacted access to care period.
And so if indeed the Supreme Court upholds the very practiced principle that you are entitled to get the emergency care that you need based on what your medical professional, that doctor says you need, that would be a good thing.
Brendan Jackson, CDC [00:43:25]
So a little bit of learning from last season, was how we already covered a lot about some of the nirsevimab issues. And we’re really looking to see what we can do to mitigate those, continue to mitigate those as much as possible.
I think some of that was related to it being a new immunization. It’s the first time we’ve sort of had a monoclonal, long acting monoclonal like this, in that space.
And there was also the supply limitations that were going on at the time. So we think that those have been resolved. There’s still some leftover supply from this year, more coming in for next season. So knock on wood. Things should be good in terms of that.
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Brendan Jackson, CDC [00:47:45]
In terms of communications last year, we were in a challenging situation overall where basically the remaining COVID funding was largely rescinded as part of a larger congressional budget deal. And so there was a larger campaign that was, that was pulled back and never released.
So CDC pulled together what funding that we could, put together a small campaign that was called the everything campaign.
Many people probably didn’t see it because there, again, there was not a large budget behind us.
We are excited this year that HHS has more funding and is planning a campaign right now. And we’re doing what we can to support that, especially as they are targeting or not, or trying to really drive up coverage in groups at higher risk, like older adults, and including by working with healthcare providers as a core strategy there.
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Brendan Jackson, CDC [00:47:45]
In terms of communications last year, we were in a challenging situation overall where basically the remaining COVID funding was largely rescinded as part of a larger congressional budget deal. And so there was a larger campaign that was, that was pulled back and never released.
So CDC pulled together what funding that we could, put together a small campaign that was called the everything campaign.
Many people probably didn’t see it because there, again, there was not a large budget behind us.
We are excited this year that HHS has more funding and is planning a campaign right now. And we’re doing what we can to support that, especially as they are targeting or not, or trying to really drive up coverage in groups at higher risk, like older adults, and including by working with healthcare providers as a core strategy there.
Jennifer McQuiston, CDC [00:11:53]
Clade II mpox is not over, it continues to circulate among cisgender men, especially those identifying as gay or bisexual.
Most cases continue to be in people who are unvaccinated, meaning they’ve never presented for a vaccine, or maybe people who got one dose of vaccine and haven’t achieved maximum levels of immune protection and could really benefit from getting that second dose, no matter how much time has passed since their first dose.
We know that people with severe immunocompromise continue to have a much higher risk for severe and fatal outcomes. We continue to have deaths due to mpox in people who were infected months ago, but, because of their immune systems being so compromised, they’ve not been able to mount an immune response. And some of them do succumb to those infections, which is always tragic.
There’s a lot of local and regional spread that’s happening. Most of our cases are not reporting international travel. So that suggests that these are homegrown, in the United States.
And we have an emerging trend of some TPOXX resistant cases. We’ve had over 50 that have been detected, including 18 new cases in at least five states in the last couple months. So, monitoring this because TPOXX has been one of our primary investigational drugs that we’ve used to treat severe infections, and we don’t want to really see resistant strains circulating in the United States. So monitoring that.
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Jennifer McQuiston, CDC [00:13:16]
We continue to really recommend two doses of Jynneos, no matter how long it’s been since the first dose. The new commercial availability of Geno, set’s been since April 1st adds some complexity to this.
The supplies that are being sent out through the Strategic National Stockpile are available right now, but projected to be phased out by August, in which case accessibility shifts to commercially available resources. And there is some concern that this could increase access issues, equitability. And so some conversations around that I think are important to have.
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Jennifer McQuiston, CDC [00:13:52]
And then we get this question a lot. No booster is recommended at this time. We don’t see epidemiologic signals of waning immunity, but we’re continuing to monitor this and assess it.
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Agam Rao, CDC [01:04:25]
In these cases, we’ve already had 58 deaths in the United States, the most deaths of any other country in the world.
And these are almost all, I would say all, severely, severely immunocompromised patients, typically with advanced HIV, CD4 counts often in the single digits who are not connected to medical care, did not know they had HIV, did not get vaccinated. Almost all of them have not been vaccinated.
So it is a really important thing that we have to work on because these consultations are just devastating. We get reconsulted and reconsulted. The patients were in the hospital for six months at a time or even longer.
They have very, very severe disease, nothing like– I mean, the typical patient, I understand that they, that there’s issues surrounding like having pigmentation and things like that. But, but these patients, my goodness, like it’s just heartbreaking to see what they’re going through. And so reaching those individuals is really important.
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Agam Rao, CDC [01:12:11]
It’s on the routine immunization schedule now. So that is a pathway for reimbursement from insurance.
And I also know that Bavarian Nordic has been working really closely with various pharmacy chains like CVS and Walgreens, and in states where pharmacists can give vaccines, it’s already available in CVS. So pharmacies where, I mean states where pharmacists can get vaccine, like in New York state, for example, they cannot, but in other states they can, and CVS already has it available. You can book it online, and Walgreens will very soon make it available. There’s also other, other pharmacies that they’ve told us about. They seem to think that a lot of pharmacies will have it available.
I can understand the stigma issue. Our hope is that because it’s part of the routine immunization schedule, that’s similar to other vaccines that are given in STD clinics and at HIV clinics, but also primary care clinics that it will be given.
I led the ACIP work group, and that’s the Advisory Committee on Immunization Practices. I led that work group that reviewed all of the data on this. And we had on our work group, many STD clinicians and HIV providers as well, who all unanimously really said that when we asked, is it going to be difficult for you to administer vaccines in your clinic, once this is commercialized, they all said, no, we routinely are giving vaccines in clinic, including in STD clinics. We are also routinely giving, you know, therapeutics for STDs in STD clinic and HIV clinic. And so this would just be rolled in.
They didn’t seem to think it would be any different for them. And we’re actually looking forward to commercialization.
Even before commercialization, there had been a– there was a trend away from health departments and more towards individual clinics providing the vaccine. And, and our hope also is that just now that it’s on the routine immunization schedule, it’s going to be something that clinicians think of when they have a patient with HIV in their office or a patient who’s presenting for STDs. And they will routinely go through all of the other vaccines on the routine immunization schedule and think about whether their patient qualifies.
Christine Oshansky, ASPR [00:33:52]
CDC monitors disease outbreaks, looking at surveillance across the surveillance in wild animals. And as well as in humans. Risk assessments are performed.
Now concurrently, the WHO collaborating centers are generating candidate vaccine viruses, to make sure that the manufacturers hav those available if needed. And likewise, the WHO essential regulatory laboratories are making sure that potency reagents are ready to go if needed.
And then our partnerships with CSL Seqirus, GSK, and Sanofi, we work with them very closely to develop those seed lots, to manufacture bulk antigen, get those into final containers if we need.
And anything that is manufactured gets placed into stability programs. So they’re always monitored at the manufacturing sites, so that they remain within specification.
Clinical trials are sometimes performed. And any data that is generated gets placed into pre-emergency use authorization living documents. So these are living documents they’re updated periodically, and they’re on file with the FDA so that we can rapidly respond if we need to go.
And with all of these, all the, all of this data in place, we strive for it to lead to faster to first doses and faster to full immunization, if the need arises.
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Lorna Meldrum, CSL Seqirus [00:44:39]
One of the areas that we are really proud of at CSL Seqirus is our partnership with BARDA at Holly Springs.
This has been a very long term partnership, 17 years, gone through several owners, but we have been responsible for that partnership for the past eight years.
The partnership began when the U.S. wanted to move away from its dependence on egg technology and was interested in new technology. So the objective for Holly Springs was to provide cell based vaccine and the adjuvant manufacturing capacity to be able to deliver 150 million doses of the vaccine in the event of a pandemic.
And from the factory being built,or the ground broken in 2006, we are really proud that in May 2022, we were declared pandemic ready.
We had been awarded seven contracts to date by BARDA.
The first and foremost was the manufacturing infrastructure working together to build the facility at Holly Springs, and then subsequently adding to that the viral pilot plant and the small scale filling facilities.
Another really important thing was some contract awarded to improve the yield of the vaccine.
If you think that egg technology has been developed over 70 years, so 70 years of year on year improvements on yield, whereas this is a new technology.
So we had a process called 3.0 that really drove the yield from the facility when we first took over the facility, the yield for the seasonal vaccine was sitting at about 2 million, and now we can produce 60 to 70 million doses of seasonal vaccine.
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Lorna Meldrum, CSL Seqirus [00:47:36]
So we have our cell culture technology at Holly Springs, because we don’t use egg, we can show a greater match to the circulating strains, which leads to greater effectiveness.
It also reduces the dependence on egg-based vaccines, if there’s a, a worry about the flock of chickens that are needed to produce vaccine, then we have the MF59 adjuvant, dose sparing to the antigen. Also adding breadth of protection across different strains.
But also because this adjuvant is used in our seasonal vaccine worldwide, we have a very extensive database to date, over 300 million doses have gone into arms.
And then we look to the future, and this is very much potential, but what we want to show is higher effectiveness, longer durability, which is one of the issues with the current mRNA vaccines, multi pathogen, and of course speed.
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Question [01:06:51]
Should there need to be a vaccination response to the circulating H5N1 in birds or cattle, should we need to vaccinate humans, what impact would that have on the availability of seasonal influenza vaccine? I guess I’m asking if, if both pandemic vaccine and seasonal vaccine can be made at the same time.
Julian Ritchey, Sanofi [01:07:18]
I’m happy to offer perspective on that. So that’s absolutely one of the key decision making factors that we bring forward in the consideration. So many of the points I mentioned in terms of the planning are looking at what impact does this have on manufacture of other products?
And many of these facilities are built in a manner where we can do this in a complementary fashion, but that’s part of the close collaboration we have with our government partners in order to determine the priority and the timing of what’s necessary.
And so fortunately our flu production is very far progressed. So this year, it wouldn’t have that kind of impact. But it’s also something we have to watch very closely in order to ensure anywhere in the process, from early stage down through fill finish, that that’s taken into careful consideration.
Lorna Meldrum, CSL Seqirus [01:08:13]
I would also reiterate what Julian has said. And it’s all to do with dialog with BARDA on when we have manufacturing.
At the moment, the manufacturing window to produce more H5N1 or H5N8 is there because our seasonal production has finished.
But if the demand was such that it was during seasonal production, then that decision would be made by BARDA, and probably based on a WHO pandemic call.
The Centers for Disease Control and Prevention (CDC) is providing technical assistance to the Michigan Department of Health and Human Services (MDHHS) as the department conducts an H5N1 seroprevalence study of individuals exposed to sick cows. The study is completely voluntary for any participants and anonymous. Data collection has been completed for the first phase and we are in laboratory and epidemiology analysis phases. MDHHS looks forward to sharing its findings when those phases are complete.
Eric Deeble, USDA [00:12:37]
We’re pleased to announce the first four states that will be participating in the pilot program, and they are Texas, New Mexico, Nebraska, and Kansas.
The participation of the states in the pilot is an important step forward in USDA’s efforts to further reduce H5N1 virus dissemination, provide further opportunities for farmers to test their herds that are known to be affected with H5N1, improve surveillance and expand our knowledge of the disease, and support an overall national program to reduce the risk of H5N1 in dairy herds.
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Eric Deeble, USDA [00:13:41]
This list of participating states is just the beginning.
And we are in close conversation with about a dozen other states who are very interested in participating as well, but it was important for us to get these four states going so that other states could watch how the program works and gain additional confidence.
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Demetre Daskalakis [00:17:09]
I’m also pleased to announce that CDC is providing technical assistance to the Michigan Department of Health and Human Services, which has launched an H5N1 seroprevalence study of people who are exposed to sick cows. So that means a study that couples surveys along with blood tests to look for exposure to H5N1.
The point of the study is to determine if there is asymptomatic infection with H5N1 among people who have worked with cows who had HPAI or H5N1 infection.
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Don Prater, FDA [00:22:55]
Last week, the agency began a second sampling survey of dairy products available at retail locations nationwide to expand our knowledge of HPAI H5N1.
This retail sampling effort is intended to address remaining geographic and product gaps from the initial sampling of the commercial milk supply that FDA conducted between April and May of this year.
The FDA’s second sampling survey is testing an expanded list of dairy products for H5N1 including products such as aged raw milk cheese, cream cheese, butter, and ice cream.
Importantly, additional samples are being taken from areas included in our previous survey to help provide a more representative picture based on the level of dairy products production that occurs in certain regions.
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Eric Deeble, USDA [00:36:57]
USDA’s Ag Research Service is conducting a study to investigate the ability to infect dairy cattle with HPAI, clade 2.3.4.4b in that experimental setting, in its labs in in Ames Iowa.
The goal of the study is to evaluate the ability to mimic clinical signs observed in naturally infected animals in a laboratory setting so that we can conduct further epidemiological study of the virus.
This initial study evaluated two routes of infection. One was an aerosol route, with yearling Holstein, and intramammary route with lactating Holstein cows.
Preliminary data shows that clinical signs observed in the field can be replicated in lactating Holsteins, utilizing an intrammammary route.
The ARS scientists are conducting the study are going to publish the findings, when the studies are completed. And I think that we may have some additional data coming out in the not distant future.
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Don Prater, FDA [00:39:03]
FDA included in our next round of retail sampling, we are including aged raw milk cheese, because that is a product that’s in interstate commerce. So that’s the one that we’re focused on in that particular survey.
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Robert Johnson, ASPR [00:42:31]
So the first question, was around kind of really a policy decision at– you know, at this point, from the ASPR perspective, we’re in agreement with the CDC’s assessment that H5N1 is currently a low public health risk. So any decision to change that would be, at a policy level, jointly across HHS and most likely with others.
And also, I will just note, that would also be a regulatory decision of course, because we wouldn’t be able to distribute product without the regulatory approval to do so.
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Eric Deeble, USDA [00:45:16]
USDA considers a single infection of a cow in a herd to be an infection for the entirety of the herd.
The testing that we have been doing has been geared towards identifying those herds that have active H5N1 infections.
The way in which we do testing, which often involves pooled samples, can make it challenging to know the number of individual animals within a herd that is infected.
However, we do know from the epidemiological work that we have accomplished that it seems that about 10% of the animals in any particular herd that is encountering this disease become infected.
And of course, as we all know, go on to recover and generally reenter lactation after a few weeks of transient illness.
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Rosemary Sifford, USDA [00:46:41]
We have been working with some collaborators to look at serology in some of those herds, but we do not have final data from that work at this time.
We are expecting that in the near future, and we’ll be sure to share information from that work is available.
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Demetre Daskalakis, CDC [00:47:55]
I think that we are definitely exploring all possibilities, like many options, in terms of testing from the perspective of H5N1.
I think, the main focus of attention currently is really working toward identifying commercial routes where we can make testing more available, especially as we approach the traditional flu season.
In terms of rapid tests, again, all on the table. But, the main focus right now is really on lab-based testing, specifically to increase access beyond public health labs as we approach the regular flu season.
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Don Prater, FDA [00:50:01]
I’m not aware of any herds that have reported that, but they would probably– I’ll defer to USDA on that.
Eric Deeble, USDA [00:50:13]
We don’t have any herds that are known to be infected that are contributing to raw milk supply off farm.
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Robert Johnson, ASPR [00:50:32]
In regards to the regulatory, I really have to defer to the FDA on that.
In general, they do the risk benefit analysis. And so it’s a standard regulatory proces.
From an ASPR perspective, we don’t influence that decision in any way. We just support the developers in terms of generating the data.
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Eric Deeble, USDA [00:51:11]
USDA issued two RFIs, one for feasibility and one for interest, to gauge sort of the technical capacity of the vaccine development community.
We got very robust participation there. And we know that a number of folks are speaking directly with the research scientists at USDA as they continue to consider the development of this.
This is going to take some time. I think I may have mentioned that there is a challenge study underway, and hopefully will be sharing out results with that, as soon as that study is completed.
And the development of a vaccine, particularly one that we know well, but find in a new species, is challenging. And so we’re working on the fundamental science and we believe that this will be an important tool for producers when it is available.
We hope that through enhanced biosecurity and additional testing that will be undertaken as you know, subsequent to the implementation of the herd status verification program, as well as ELAP, that we will be able to eliminate this disease from the dairy herd in the absence of a vaccine, although that we believe that they may be helpful down the line.
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Don Prater, FDA [00:56:58]
We do plan to sample approximately 155 dairy products as part of this next round of sampling.
I don’t have the specific number of states, but these samples will include some different products than what we had sampled previously and also some different geographic regions.
So hope that’s helpful.
Question [00:57:20]
And how– and the timeline for the results?
Don Prater, FDA [00:57:24]
I think it’s probably still gonna be several weeks away for the results to be published. I don’t have a precise time.
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Eric Deeble, USDA [01:02:49]
While it is H5N1 does appear to operate very differently in dairy cattle than it does in poultry. We have no evidence of respiratory transmission in any case involving dairy cattle.
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Rosemary Sifford, USDA [01:01:22]
I would just reiterate that point that in all of the herds that we have found to be affected, we have found epidemiological links to other herds, whether that be movement of people or equipment or vehicles, that there have been movements between these herds and other affected herds.
Has CDC identified any differences in severity from KP.3 or LB.1 infections?
There is currently no evidence that KP.3 or LB.1 cause more severe disease. CDC will continue to track SARS-CoV-2 variants and is working to better understand the potential impact on public health.
Is it accurate to describe KP.3 and LB.1 as closely related?
KP.3 and LB.1 variants can be described as closely related as they both are sublineages of JN.1
Robert Califf, FDA [00:09:00]
It’s a great time to be FDA commissioner, because everywhere in the world I go, people say the U.S. is leading the world in technology, development, innovation, new gadgets of all types, new drugs, you name it, yet these advantages unfortunately are not resulting in superior health and outcomes for the U.S. population or for most individuals in the U.S. In fact, U.S. health outcomes are currently deteriorating.
The intersection of biomedical science, technology, and communication have handled with a different strategy, with good policies, investment, and collaboration and communication could usher in a new era.
There’s an exception for type one diabetes, which I believe is on the verge of a major breakthrough in terms of the biology and biological therapies that could make an enormous difference for this special population of people with diabetes.
But on the other hand for the larger epidemic of type two diabetes, we’re failing right now. And I don’t say that lightly. I’ll show you data, which I think supports that view and we need to change our strategy to do better.
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Robert Califf, FDA [00:12:20]
I don’t need to tell you this. And Dr. Bob told me not to bother with these slides, but I sort of have to show them to build a case I want to make, we got a lot of people with with both diagnosed and undiagnosed diabetes in the United States.
The maps that you are all used to looking at are striking and continue to get darker and darker as more and more states develop very high rates of obesity and diabetes over time.
You have now, at least according to some sources, surpassed cancer as the leading economic cost of healthcare in the United States. This is an honor I’m not sure I would want to have, but it does give you a lot of power to do things to make this better.
And of course you’re dealing with a chronic disease, which has all the same issues related to different outcomes in this country related to a number of factors, including race being an important factor, urban-rural status is one that’s particularly advancing right now where people that live in rural areas are doing worse and worse relative to urban counterparts for a whole variety of reasons. And it’s very much reflected in the data about diabetes.
And income does turn out to be an important factor. It’s said that money can’t make you happy, but not having enough money to subsist and to pay for your medicines definitely is a factor in the outcomes of chronic disease and in the incidence of diabetes in particular.
And of course, this is not just a problem of people my age. It’s a problem that’s brewing around our society.
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Robert Califf, FDA [00:29:15]
I think still underused in clinical care for the most part, with some add-on benefits shown at the bottom, but of course, the big new thing would be the GLP-1 receptor agonist and similar drugs, which are now approved for type two diabetes, weight management and cardiovascular risk reduction. And again, I think vastly underused.
But the amazing thing is the additional indications for which there’s preliminary data. And we do have a saying at the FDA, in God we trust, all others must bring high quality evidence.
So for these other indications, like alcohol, smoking, gambling, Parkinson’s, Nash, and Alzheimer’s get those trials done as quickly as you can. We need to know for which indications these drugs are beneficial and which are just a hope, which is not going to turn out to be true, once we have the data.
And it’s amazing. Once there’s a hit in an area like this, the pipeline is enormous, with many variations on the theme. As I’ve said, it’s not the FDA’s job to figure out which one of these is best. That’s something we really need you all to focus on and help figure out for your patients.
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Robert Califf, FDA [00:30:33]
Now a slight diversion to type one diabetes. And mostly all I want to say here is to express the enthusiasm that we have about type one diabetes and the verge of success that we hope we’re on, in terms of the advent of highly effective cell and tissue therapies and other approaches to type one diabetes.
It is so a very complicated field with a lot of opportunity for people who think their treatments are effective to make mistakes. And so this balance of promoting innovation and protecting the safety is something that we’re going to have to work on together.
And I’d also point out that the short-term outcomes are crucial and very important, and we have to make a lot of our decisions based on short-term outcomes, but we’re going to need systems driven by the clinical community of long term follow up of people.
If we have a highly effective treatment, doesn’t necessarily mean we know what’s going to happen 10 to 20 years from now in this particular area.
So we’re back to in God we trust, all others bring high quality evidence.
This is just some examples of what we’re seeing now at the FDA. These are just examples, not meant to signal out any as being particularly effective at this point, but very much worth keeping an eye on.
Then we get to type two diabetes and, I’m also enthusiastic, but it’s a whole different game in my view of figuring out how we get technology to the right people and solutions to the right people at the right time.
One of my favorite sayings was from Ed Yong in The Atlantic. It was about the pandemic, but he pointed out that technological solutions tend to rise in the society’s penthouses and epidemics seep into its cracks.
And the point here is that if you look at all the technology being developed in diabetes, and I saw this very much when I was working at Google or Alphabet, despite all the efforts, there was a great tendency for the best things to be taken up by people with PhDs and living in urban areas. Most of our people were left out and haven’t caught on as much.
So this is a thing that we really need to work on, uh, and figure out how to get effective technologies and interventions to people in rural areas and the underserved. And it’s not going to be easy.
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Question [00:45:05]
You shared with me, you have this little bit of a nightmare, that I think involved like your grandchildren coming to you and asking you about something–
Robert Califf, FDA [00:45:15]
Oh yeah, well, yeah. It’s– it goes something like this.
My great grandchildren are reading a history book and they read about this country called the United States that had a commissioner that was in charge of food and drugs called Dr. Califf.
And he allowed the country to eat so much that they gained a pound per year on average as a country, and then encouraged people to develop a drug that costs $20,000 a year to reverse it. And the great grandchildren are saying what kind of idiot would do that?
So I hope we can deal with this proximal end. I’m all– I love the GLP-1. You mentioned, the saliva story, and I was very involved in one of the first outcome trials in GLP-1s as an academic. I love it.
But we got to do something about what’s happening to our children and teenagers.
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Robert Califf, FDA [01:08:47]
Obviously this is a critical area. Our levers are actually limited. I introduced a couple of these things, which I think are sort of like the baseline state, like putting the label on the front of the pack. How can we not do that? But, there are a lot of people opposed to it. I got to tell you.
Giving people, like if it says healthy on the package and it actually means a constituent food groups that are actually healthy, if you eat them in combination, simple things that people can do.
But we got to really depend on the professional community because we sort of stop at the point at which there’s a consensus in the professional community of things that Congress has given us authority to do. And beyond that, it’s a matter of how you integrate all this.
Tim Uyeki, CDC [00:12:37]
Now, the virus infects the respiratory tract of cows, but is very much concentrated in the mammary, in raw cow milk, it infects the mammary tissues.
So if one were to get exposed to respiratory secretions being up very, very close, for example, giving oral gastric tube fluid resuscitation to a cow, you’re right in the cow’s face close with nasal secretions, or if you were to get splashed by raw cow milk, or to get cow milk contaminated on your hands and then touch your mucus membranes, that could lead to infection.
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Tim Uyeki, CDC [00:19:42]
So in the U.S., as I mentioned, we’ve had three human cases associated with dairy cow exposures this year, one in Texas, that person, you saw the figure on the other slide. It was bilateral conjunctivitis only. We had a case in Michigan only had unilateral conjunctivitis.
And then the most recent case in Michigan had upper respiratory tract symptoms without fever. Did report, about 10 days into the illness, some watery eyes for a couple of days. I think that was actually due to allergies. And the household contact also had seasonal allergies.
So none of these individuals were hospitalized. They were all recommended for home isolation to be away from their household.
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Tim Uyeki, CDC [00:24:47]
So influenza tests that are available in clinical settings cannot specifically identify H5N1 virus. There are many, many different kinds of influenza tests available in the outpatient setting, in emergency departments and also, for hospitalized patients, but they they’re either detect influenza A or influenza B. And they can’t tell you that a positive result for influenza A is H5N1 virus.
So if you get a positive result for influenza A, it could be seasonal influenza A virus infection, right?
So right now seasonal influenza A and B virus activity in the U.S. is low, but it’s not zero. And we do have cases of seasonal influenza during the summer months. And occasionally there are people who are hospitalized with pneumonia due to seasonal influenza.
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Tim Uyeki, CDC [00:50:50]
In terms of respiratory protection, the recommendation is an N95 respirator, not a surgical face mask. Definitely the recommendation is for eye protection. And, as I mentioned, we’ve had two cases of workers with conjunctivitis and so goggles or a face shield.
But as Dr Maderas recommended, this may not necessarily be practical given the environmental conditions. So throughout the U.S., every day, it’s only getting warmer and more humid. And Dr Maderas mentioned even for healthcare personnel, the challenges of wearing goggles or face shield and fogging up and so forth.
So, what we can say is what the recommendations are. We can post all of the PPE that are recommended. We can post the guidance from CDC and NIOSH in there.
But we also realize the reality is that workers may not comply. And so I think that we all have to work closely together, including with farm workers and farm owners and the dairy industry to see what might actually be possible, and who are those at most highest risk of exposure to this virus and infection.
And it may be that it’s people who are definitely working with cows that are symptomatic, that are sick, and that those who are working with– who are doing milking in the milking parlor. And the reason is, again, we’ve had two cases of conjunctivitis. One of those cases was splashed in the eye with raw cow milk. And that resulted in conjunctivitis. We believe that was sort of the– how transmission occurred.
And so, I think we can make these recommendations, but I think all of us realize that this may be a bit challenging for workers to comply with that.
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Tim Uyeki, CDC [01:01:39]
I think that that’s getting at the practical issues. Now, ideally for healthcare personnel, the recommendation is you want to be fit tested, and actually it’s annual fit testing, right, for N95 because there are many, many different models of N95 respirators, there are many different sizes, and one model and one size does not fit all.
However, the reality is that we’ve never made this recommendation for workers at dairy farms before. And my understanding is that typically on these dairy farms, nobody wears any kind of personal protective equipment, at least that’s recommended until very recently.
So when you implement that, that raises a good question. Now I think most people in the U.S. are pretty familiar with the last four years of the COVID 19 pandemic and many of could purchase or actually could receive these KN95 respirators, right? So it’s not formal fit testing, but you mold it to your face and you get a proper fit. And so that is much better.
You get a proper fit, some kind of fit. Maybe it’s not formal fit testing, compared to using no mask or using a surgical mask that maybe is not so well fitting. It’s a very good question because formal fit testing is not done in the farm setting. It’s not done with a portable fit testing equipment.
So I don’t have the answer. And, that’s another thing where NIOSH can make these recommendations, but the practical implications of the reality at the farm setting level may not be actually be conducive to doing the formal fit testing.
And so some kind of good approximate seal I think is going to be better than none.
Sonja Olsen, CDC [00:18:20]
There’s the wastewater data. So this we recently started showing on our website. As I said, it is several hundred sites, it depends on who’s reporting each week and the quality of the data, but right now we’ve set up an analytic tool to compare the levels we’re currently seeing and those to the flu data that we were seeing during the influenza season in 2023 to 2024. And then we’re flagging those that are at the 80th or higher percentile.
Once a state flags or a site, a wastewater site, flags, we do outreach to state and local partners in these high areas. And we also notify others in the interagency space, including USDA and FDA.
So current wastewater methods in this system detect influenza A viruses, but don’t distinguish the subtype or source of the influenza A. So it could be seasonal flu circulation in humans, or it could also reflect H5N1 in animals.
We know that many different sources of waste often feed into these systems and we’re learning more and more, as we work with states to understand some of the results. There are also groups that are currently testing directly for H5 in wastewater that you may have heard about, including one that I think now has a public dashboard.
And I’ll just mention that CDC is in the process to begin to validate an H5 assay that could be used more broadly as part of wastewater surveillance throughout the United States.
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Sonja Olsen, CDC [00:21:13]
So in addition to all those surveillance activities, we’re also working with health and agricultural partners at the local, state and federal level, as well as the affected farms to conduct some epidemiologic studies. And why do we want to do this?
Well there’s still a lot of important public health questions we want to answer. And those include, is there evidence of infection with these viruses in the exposed populations more broadly? If we find infections what’s the spectrum of illness or the rate of asymptomatic infections? What are the types of exposure specific exposures on these farms that could help us more better tailor our guidance to workers? And specifically, are there behaviors associated with these infections, or protection from the virus, that we can learn.
So to do this, we do an assess– we’re going to do an assessment for risk for both symptomatic and asymptomatic. And this is going to be done through collecting specimens, including serum, from populations of farm workers who have been exposed to infected cattle, and do that in conjunction with a survey to assess what are the specific exposures.
So these will take a while to do, but I think will be very helpful for us to learn more about how best to really protect workers and what is the extent of the infection, if any.
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Sonja Olsen, CDC [00:51:28]
I think that this is still an avian virus and so it’s not well adapted to the receptors that we have in our respiratory tract. And, so that’s a good thing. And I think the one or so adaptations we’re seeing probably are more likely to do with the clinical course than the transmission.
I think if we started to see mutations in the virus that were more associated with receptor binding, and ability to transmit, that would be concerning.
But I think, it goes without saying, that any novel flu virus is a concern and we treat it as if it might be the next pandemic, which is why we take it seriously and sort of ramp up a response.
I mean, this is still largely a disease in cattle. It’s an animal problem. And, but we can’t – we don’t have the luxury of letting our guard down. So I think that’s why we’re doing everything we’re doing.
Kimberly Armstrong, ASPR [00:23:20]
On the smallpox vaccine front, the vaccine continues to be made available to jurisdictions for the ongoing mpox response. And this is expected to continue through August 2024.
And Bavarian Nordic is now making the vaccine available commercially. The SNS or the Strategic National Stockpile will continue to make the Jynneos vaccine available for uninsured and underinsured individuals in the United States.
Question [00:24:07]
Mr. Secretary, two questions on EMTALA.
I’m wondering first, if you could give us a sense of how busy that work is keeping CMS, I mean, give us a sense of the scope of their investigations.
And then second, I’m wondering if you can talk just a bit to us on how it relates to the other tools in your toolbox. What’s at stake? Thanks.
Xavier Becerra, HHS [00:24:26]
And I’ll answer that. And I will invite the senators to answer, because I know they’ve been doing work to try to ensure rights, regardless of whatever the Supreme Court does, with regard to EMTALA.
CMS continues to request information from individuals who think they may have been deprived of their rights as they sought emergency healthcare. CMS will continue to follow up on any reports that we receive of people being discriminated against when it comes to receiving the healthcare they need in emergency circumstances. And we will take action where we can.
Obviously, the Supreme Court case was based on a report that we received and then acted on and the deprivation of access to healthcare, by a woman in Idaho. And so we’ll continue to do that.
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Xavier Becerra, HHS [00:25:47]
It used to be that you wouldn’t have to think twice.
If you were facing an emergency or someone you loved was facing an emergency, 9-1-1 you call, and you know that they’re going to get access to the care that they need, likely in an emergency room, regardless of what your circumstance was.
If you were in an emergency circumstance, a doctor would decide what your care would be to keep you alive or to stabilize you, not a politician, not even a judge, because in the moment of your need, that politician and judge are far away from you, it’s the doctor who’s in front of you.
And we want to keep it that way, that doctors will decide the care you need, including in emergency circumstances.
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Xavier Becerra, HHS [00:00:05]
It is a contract that runs one year and that can be renewed every year for up to nine years.
And what we’re simply doing is going through a process to make sure we have a contract that protects the interests of the tens of millions of Americans who rely on those call centers to get the information they need for Medicare, ACA health insurance coverage.
We went through a request for information where we solicited information. We then submitted the request for proposals, and now we’ll see if we received proposals, CMS will work through the process the way it’s typically done, and they will see if there are bids and then hopefully by some point next year, we’ll find out if we have a new contractor or we may remain with the same contractor.
Either way, what we want to do is make sure there’s continuity in the operations at these call centers. So no American, whether for Medicare or for the ACA insurance coverage, finds disruption in accessing the care that they need.
Dollar Tree is committed to selling quality food and products, maintaining a safe environment for associates and customers, and complying with all laws and regulations. Under our new management team, we are on a journey to transform our business and continue to take steps to significantly enhance and strengthen our compliance and safety programs and capabilities, including our process for quickly and effectively executing product recalls. We are building and enhancing our efforts to prevent and detect violations, and when a compliance issue does occur, we work to remediate it promptly and fully. As previously disclosed, in October 2023 Dollar Tree took immediate action and began executing a recall of WanaBana’s Apple Cinnamon Fruit Puree Pouch upon being notified of the issue with the product. We continue to cooperate with FDA on this matter.
Todd Davis, CDC [00:18:12]
This also includes making sure that commercial laboratories that are receiving and testing specimens are also able to subtype those viruses.
So a routine part of the process with commercial laboratories of course, is anytime a sample tests influenza A positive, but as subtype negative, that those samples are quickly submitted to a state public health laboratory for additional subtyping, or if they get an interesting result, for example, if they detect influenza A(H1) but not (H1N1)pdm09 in their assays, that those are also subtyped or characterized with additional testing, to be sure that we’re picking up those potential novel influenza A infections.
So that’s fairly routine procedures that are coordinated between commercial laboratories and state public health laboratories. And that includes submission of samples that can also be tested using CDC’s H5 assay, upper respiratory specimens, lower respiratory tract specimens, and now paired nasopharyngeal and conjunctival specimens. I’ll talk a little bit more about that in a minute.
But in addition to that routine processing, we’re also asking commercial laboratories to submit influenza A and influenza B positive specimens that have not undergone influenza subtyping, to be sure that we’re not missing any novel influenza A infections in those types of samples. So CDC’s currently working with commercial laboratories to determine what the appropriate number of samples would be for them to submit those to state public health laboratories, NIRCs or ISCs for additional characterization, making sure that those samples meet established cutoffs for our testing algorithm and making sure that those are done in a timely manner so that we can get subtyping results on those samples.
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Todd Davis, CDC [00:20:07]
One of the more recent things we have been able to do with FDA is to request and receive enforcement discretion to now allow state public health laboratories to use conjunctival swabs for a diagnostic test using CDC’s H5 assay.
These have to be paired with the nasopharyngeal swab, per the criteria of the enforcement discretion. And there also has to be in-house verification performance studies, per CMS guidelines, at the state public health laboratories that are performing this testing.
But that’s given us a number of additional samples, and a sample type, that previously was not permitted for testing using CDC’s H5 assay.
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Todd Davis, CDC [00:22:46]
We’ve had some requests from quite a few public health departments to provide recommendations and specific protocols on actually collecting conjunctival samples from individuals. And so working on some graphics and a specific SOP that we hope to be able to distribute very soon.
And last but not least, also working with FDA to consider adding universal transport media as a sample collection matrix, as opposed to only virus transport media in order to use a broader subset of media for use use in CDCs H5 assay.
So something that’s in the works. And hope to be able to provide some more details on that soon.
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Question [00:23:52]
You spoke about it earlier with the 2022 outbreak, and you mentioned monitoring cases out to 10 days. What’s– how long do you monitor for this outbreak? How long are the cases being monitored for this outbreak?
Todd Davis, CDC [00:24:07]
Yeah, we follow the same monitoring strategy for 10 days. I think, keep in mind, in the case of poultry outbreaks, poultry flocks are culled, after they are detected. And so we have really a day one for those individuals that have been exposed to those flocks, after the culling has taken place.
It’s a different scenario with the infected dairy cattle, where they’re allowed to recover. And so it’s a little bit harder to gauge exactly when that monitoring period begins.
Topline:
To date, the totality of evidence continues to indicate that the commercial milk supply is safe. The FDA recognizes the importance of ensuring the continued safety of the commercial milk supply and remains committed to providing updates of its scientific findings. The FDA will continue to evaluate ongoing studies related to H5N1 in milk as part of our risk management decisions for public health.
While laboratory benchtop studies provide important, useful information, it is challenging to simulate real world commercial processing conditions on the benchtop. This is why the FDA is conducting a pasteurization study designed to better replicate real-world conditions testing of milk that is more representative of conditions encountered in actual processing facilities. Results from the FDA’s study will help further the agency’s understanding of pasteurization efficacy against anticipated concentrations of virus under real-world processing conditions.
Additional Background:
To be clear, the NIH has not confirmed the presence of active H5N1 virus in pasteurized milk but rather has released some preliminary data using benchtop equipment to approximate pasteurization conditions. The study reflected experimental conditions, and should not be used to draw any conclusions about the safety of the U.S. milk supply.
The FDA is using multiple data sources and research studies to build a strong body of evidence regarding the effectiveness of the milk safety system. The FDA conducted an initial survey of 297 retail dairy products collected at retail locations in 17 states that represented products produced at 132 processing locations in 38 states. All of the samples were found to be negative for viable H5N1 virus. These results underscore the opportunity to conduct additional studies that closely replicate real world conditions. The FDA, in partnership with USDA, is conducting pasteurization validation studies – including the use of a homogenizer and continuous flow pasteurizer.
Generally, benchtop thermal inactivation studies provide data and information that help us understand the thermal stability of different pathogens. But there are numerous considerations that affect how results of these studies should be interpreted because laboratory equipment and commercial pasteurization systems can differ in important ways.
· Laboratory benchtop equipment used in these thermal inactivation studies, such as thermal blocks in PCR machines, can be difficult to heat milk consistently and thoroughly to the process temperature.
· The sample types used can vary between studies and may not be representative of the milk typically entering pasteurization as part of commercial milk processing.
To better understand relationships between viable viral loads over different times and temperatures, some benchtop studies start with very high viral loads, which may not be representative of what we expect to see in the real world.
Because benchtop studies have limits in their ability to validate real-world pasteurization, the FDA is conducting a pasteurization validation study in a pilot scale system, utilizing a continuous flow pasteurizer and a homogenizer, as appropriate, to reproduce real-world processing conditions.
At this time, the FDA has prioritized research using continuous flow pasteurization equipment because it is representative of a common industry system, rapidly heating milk to process temperatures and measuring the thermal inactivation that occurs in the holding tube. This work is currently underway, and we think it is the best way to model thermal inactivation that will be directly applicable to commercial scale pasteurization processes.
Furthermore, a critical step in the scientific confirmation process includes testing of milk that is more representative of conditions encountered in actual processing facilities. Milk routed to commercial use is typically pooled in large amounts from numerous healthy cows and comingled from numerous farms before pasteurizing and processing. The FDA is continuing to test samples of pooled raw milk from individual farms. This information will be used as a basis to characterize potential virus levels that pasteurization may encounter – and will inform studies to further validate pasteurization efficacy.
For the latest updates from the FDA visit: https://www.fda.gov/food/alerts-advisories-safety-information/updates-highly-pathogenic-avian-influenza-hpai#additionalresources
Questions:
1) Why hasn’t FDA required longer or hotter pasteurization, to reduce the risk of H5N1 infection?
All of the testing data available to the FDA indicates that the pasteurization processes currently used by commercial milk producers in the United States are effective at inactivating H5N1. Many processors use temperatures that are greater, often much greater than the minimum standards. However, excessive thermal processing can affect the quality of the product, such as resulting in fluid milk with a cooked flavor. Given the technical specifications of current manufacturing equipment in use by processors and the potential negative impact on the production of products such as cheese where higher temperatures may alter key components like proteins, the United States would hesitate to change pasteurization parameters without data to demonstrate a public health need.
2) Why has FDA delayed releasing results from its pasteurization validation study?
As previously communicated, the U.S. government partners have been working with deliberate speed on a wide range of studies looking at milk along all stages of production – on the farm, during processing and on shelves - with well- established methodologies used previously to confirm pasteurization effectiveness for known pathogens. The FDA is committed to sharing further analyses and results from additional sampling and other surveillance activities in the near future. The results when available will be posted here: Updates on Highly Pathogenic Avian Influenza (HPAI) FDA.
It is important to reiterate that this work is a top priority for the agency and we are proceeding in an efficient, methodical, stepwise, and scientific fashion to ensure the continued effectiveness of the federal-state milk safety system and reinforce our current assessment that the commercial milk supply is safe. Sound science is critical to informing public health decisions like those made by the FDA related to food safety and we take this current situation and the safety of the milk supply very seriously. We recognize the importance of releasing further, actionable information.
Mark Lyons, USDA [00:15:38]
As far as knowing where we are in this outbreak, I don’t know that we know that at this point, I think, again, as we have more of these programs come into play and everything, ultimately that’ll help us kind of better understand kind of the full scope, the full extent, of what this outbreak is. As you do see as the numbers to kind of increase in some of these states.
So we’ve seen increases in Michigan, Idaho, as disease does become present in these states. We do see it as kind of a naive population where we see those numbers go up that’s expected. That’s not necessarily alarming in the sense of we understand how this disease spreads.
However, to get really further ahead in this space. Again, it goes back to the biosecurity we’re really wanting all industries all to really up their biosecurity, have those enhanced biosecurity plans. We do have through our funding mechanisms, again, options for unaffected, as well as affected herds to both be able to increase biosecurity plans on site to one, keep disease out of their herds. And two, to keep disease limited if it would get into their herds.
So ultimately that’s gonna be the thing that gets us through and gets this kind of out of this disease outbreak.
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Nirav Shah, CDC [00:19:43]
I’m hesitant to attribute the high CT value to anything on the collection side. It’s just as possible that it was an individual who was, whose symptoms were so mild, such that there just wasn’t much virus circulating, but we’ll get back to you with additional details and discussion on that.
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Question [00:20:02]
I saw in the Michigan report, it talked about shared workers being that only transmission link between dairy and poultry. I mean, have you looked into the possibility that infected workers were the vector? Or is there a reason that you think contaminated clothing is more likely? Thanks.
Kammy Johnson, APHIS [00:20:22]
That’s a great question. And thank you for bringing that up.
When we look at those genetic sequences, we do see that there are relationships and between those viruses, and we are relying on our public health colleagues to tell us and have some indicator on whether or not people are infected.
We do know from previous scientific work that shared workers, acting as inadvertent carriers, on clothing and boots, have been identified in outbreaks in prior outbreaks of this virus on poultry farms.
So we just were relying again on inferring from previous experiences to know to know that that is an identified risk factor.
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David Boucher, ASPR [00:23:54]
We announced a few weeks ago that we’re moving forward with fill of about 4.8 million dose equivalents of bulk antigen. That is moving along well.
I think when we had announced that, we had talked about a three to four month timeline, we’ve been able to pull that into the left, and doses manufacturing should be complete starting mid-July, and then going through first couple of weeks of August. So on track there.
No plans at this time to manufacture, procure more doses. More to follow though, if that changes.
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Mark Lyons, USDA [00:34:07]
So 11 herds have signed up and are participating in the financial support mechanisms for affected herds. So of the 94 affected herds, 11 of them have now signed up for that financial support mechanism.
There are conversations happening with about 20 states. I think it is right now, where we’ve had conversations with states, conversations with herds, on enrolling in the voluntary HPAI dairy status program that was announced, and the pilot began on June 3rd.
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Kammy Johnson, APHIS [00:37:39]
I’ll try to give you the nuances of what we know and don’t know about the cats.
We don’t have any evidence that they are involved in spreading the virus further. And again, we lean on the genomic sequencing of the viruses to help us make that interpretation.
But with that said, we do not fully understand whether or not they are capable of transmitting. They can obviously be very effective carriers on their fur and their feet, so they can act as fomites. So that is one possibility, of helping, if they’re doing within herd spread.
But again, most of these cats are, have very serious neurologic symptoms and very serious health outcomes because of that. So again, they don’t, you know, unfortunately they a bit of a canary in a coal mine for some instances, and because of their early onset and their very serious outcomes.
So I hope that’s a long way of saying, we still don’t have a very clear picture, but we don’t have any evidence that they are capable of transmitting it.
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Mark Lyons, USDA [00:40:46]
I don’t know that I have those numbers either. I know it’s a high percent, we’ve had a very high percentage that we’re able to actually like get into sequencing and get good analyses out of.
So, I like we have the best people possible in that space work and high confidence in their ability to kind of get those sequences pulled from the, a very large majority of all samples.
And I would echo what Dr. Johnson said, as far as kind of the numbers again, with these programs, we’re seeing increases in testing. That’s what we’re wanting to see. That’s really working well.
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Kammy Johnson, APHIS [00:44:02]
I would like to remind folks that while we have seen spillover into those wild birds and peri-domestics, the rest of that story, that what you’re seeing is the numerator side of that, right? The number that were positive. What we haven’t put in this report specifically is the denominator and that those were of the, there was a significantly higher number of animals tested, in the hundreds on some of those farms when those animals were found.
So again, small numbers, but significant, but not cause for alarm. So I think that’s another way to put that in context of, you know, and again, we’re not seeing that we don’t have any evidence that they are going on and transmitting. It doesn’t mean it isn’t possible, but again, that’s part of why we’re why we’re capturing the information.
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Nirav Shah, CDC [00:45:27]
That is one reason why we’d like to continue the ongoing work to study what you’re referring to as the carriage or the likelihood of just having the virus somewhere in your body, but not actually having it be causing any type of illness. And so that’s one of the aims of the studies that you’ve heard us here at CDC talk about that we’d like to really do and understand.
And that gets to the heart of your question. It’s not that there’s a limitation on the amount of testing that we can be doing. We have ample amount and supply of testing, but we want to know what those tests mean. And if by testing somebody you’re happening just to pick up a stray amount of virus from their nasal passage, but not actually detecting someone who’s clinically ill who requires medication, who could pass it on to somebody else, then we’ve got to really kind of evaluate what we’re doing or accomplishing by that testing.
To date, the data that we’ve seen suggests that testing gives us actionable data when it is not just someone who’s been exposed, but rather someone who’s exposed, but symptomatic. We are always looking to evaluate that view though.
And if we were to generate data, to suggest that testing individuals who have just been exposed leads to a high number of positives, that we would then take subsequent clinical or public health action on, that’s a discussion that would then cause a change in our testing approach, but thus far, the data that we’ve seen over the past few decades with influenza suggests that testing both for exposed and symptomatic folks gets us right in that sweet spot.
This report discusses the concerns about a multicountry detection of influenza viruses named A(H1N1)pdm09. This virus has two mutations in the neuraminidase that occurred naturally and have not been seen together previously. In laboratory tests, these viruses were found to be about 13 to 16 times less sensitive to oseltamivir, than those without this combination of mutations. There are no established criteria for determining clinically relevant oseltamivir resistance based on laboratory testing. For perspective, another mutation called H275Y makes the virus 500 to 1000 times less sensitive to oseltamivir in the laboratory test.
These mutated viruses retained sensitivity to other anti-influenza medications, including a newer one, baloxavir marboxil. There are no immediate implications to change decisions for clinical care. Also, getting vaccinated against the flu can offer protection from illness caused by viruses with or without these mutations.
It is unknown how widely these mutated viruses will circulate in the upcoming season. It is important to continue monitoring the spread of these viruses and the evolution of these viruses as they may acquire other mutations that could further impact the usefulness of oseltamivir or other antiviral medications.
The Colorado Department of Public Health and Environment received the letter from the FDA last week and shared it with the Colorado Department of Agriculture. Our two agencies have been working together closely to respond to cases of avian flu, and we will continue to do so. We are currently collaborating to implement USDA’s voluntary testing program and working to develop a voluntary testing program for producers.
Kevin Hall, NIH [01:16:53]
I find myself in this very interesting position where I am very much an advocate of understanding mechanisms, because if we have 60 to 70% of the food supply is being categorized in this way, if we don’t understand what the potential mechanisms are by which foods in this broad category might lead to positive health outcomes, negative health outcomes, neutral health outcomes, then I think we’re gonna make very limited progress.
At the same time, I also hear that, you know, we can’t avoid this question and we can’t avoid this terminology, given the mountain of epidemiological data that are out there. We have to answer the question. And I think if we purposely just try to let this play its course, we’re going to run into the idea that we’re just dodging it, right? We’re not really trying to tackle this issue. And my view is we need to tackle the issue and we need to capitalize on this public awareness and this interest to generate the kinds of data that we actually need to make actionable changes.
If it turns out at the end of the day that this concept adds nothing beyond what we already know about what makes up a healthy diet, we need the data to show that. And that would be, I think, a really important outcome of research in this area. If it turns out we’re surprised and we find something is actually happening, that’s beyond what we normally think about–
I mean, energy density is the stupidest example of that, right? It’s something that’s been out there forever, but it’s not captured by the healthy eating index, right. It’s below the radar, but it’s a really simple idea that has been studied for a very, very long period of time. If it turns out in our study that we can create a diet that is 80% of calories from ultra processed food that has low energy density, that results in the similar degree of weight loss as the minimally processed diet, that’s I think a super important piece of information that will go a long way to driving what it is about ultra processed foods that is in– is not associated with some outcome, in this case energy intake.
But yeah, I just don’t want to be accused of dodging the question, which is, I think a lot of what the public pushback is and public health pushback is when you argue about definitions.
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Julie Hess, USDA [01;21;47]
I’ll echo a lot of what Dr. Hall has said already.
I think one thing that we can benefit from this research on ultra processed foods, while I’m not personally convinced that it’s a useful construct, I think if we get useful research on energy density, if we get useful research on eating rate and texture of foods, because we’re investigating ultra processed foods, that’s a win for public health.
So insofar as we could see benefits to public health from this research, I think it’s worthwhile. Is there something to ultra processed foods? I think we will know hopefully soon enough.
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Kevin Hall, NIH [01;23;04]
I’ll certainly say that there’s a lot of resistance to the idea, especially among the team of folks who developed the Nova system, who seemed intentionally, even before a lot of the mountain of epidemiological data was in, was that the idea of a healthy ultra processed food was an oxymoron.
I don’t think it is.
And the question is, you know, is there something beyond the dietary guidelines, healthy eating index, what factors beyond that might be driving some of the issues with some categories of ultra processed foods and not others?
And obviously as Julie’s study nicely showed, you can create a very highly ultra processed diet that’s meeting the Dietary Guidelines for Americans. I guess that open question is, is that just mean that the Dietary Guidelines for Americans has a, a gaping hole in it? I think that’s what a lot of the folks who push the ultra processed food narrative would say.
But I think that until we understand the mechanisms by which these epidemiological associations are being, seeming to mount every day, that we just don’t know the answer to that question. And so only by doing the kinds of trials that have started to occur will we have answers to those questions.
We have received the letter and are looking at their recommendations, and raw milk sales for human consumption is not allowed in North Carolina. Here is a link to the General Statute. https://www.ncleg.net/enactedlegislation/statutes/html/bysection/chapter_106/gs_106-266.35.html
No. There are no plans to conduct surveillance of raw milk for H5N1 and there are no plans for restrictions on raw milk sales due to the outbreak. In Wyoming, raw milk is a product that is able to be sold under the Wyoming Food Freedom Act. Under that statute, there is no regulation of certain products (like raw milk) sold from producers directly to the informed end consumers. Because of this, foods sold under the Wyoming Food Freedom Act are not licensed or regulated by the WDA so there is no structure in place to conduct surveillance or place restrictions on sales.
Iowa’s raw milk law explicitly precludes the Iowa Department of Agriculture and Land Stewardship from licensing and regulating raw milk dairies.
However, if dairy cattle within Iowa are experiencing clinical symptoms consistent with HPAI, they should contact the Iowa Department of Agriculture and Land Stewardship and we can work with them to collect samples for testing.
1)How have states responded to FDA’s letter?
The FDA is actively and regularly meeting with its regulatory partners throughout the HPAI H5N1 virus response and has had multiple engagements with them on the topic of the intrastate sale of raw milk for human consumption. The agency has ensured that our state regulatory partners are aware of our concerns and recommendations, including by sharing and communicating directly, and by making this letter available on our website.
The FDA will provide support to our regulatory partners that request assistance with the recommendations outlined in the letter. The FDA appreciates the close coordination it continues to have with our state partners on the HPAI H5N1 virus response.
2) Does FDA plan to do any surveillance or restrictions for raw milk derived products that are sold interstate, like cheese?
Any raw milk cheeses sold in interstate commerce for human consumption must comply with FDA requirements, including certain types of raw milk cheese must be aged at least 60 days in accordance with FDA regulations (21 CFR 133). The FDA is continuing to gather data, conduct testing, and support research related to the safety of dairy products and H5N1 HPAIV, including aged raw milk cheeses.
The FDA has also recommended on our HPAI website that industry does not manufacture or sell raw milk or raw milk cheese products made with milk from cows showing symptoms of illness, including those infected with avian influenza viruses or exposed to those infected with avian influenza viruses. By exposure, we generally mean cattle located on a premises with cattle with suspected or confirmed HPAI A (H5N1). Given the variety of premises sizes and the potential for state requirements, the FDA recommends producers consult with state regulatory officials and their veterinarian for further guidance. The FDA also recommends that milk from exposed, asymptomatic cattle only be used for pasteurized milk and milk products whether for human or animal feed channels. The FDA recommends that premises test for HPAI viruses in pooled milk prior to resuming commerce in unpasteurized dairy products following apparent resolution of illnesses on the premises.
There are 53 licensed retail raw dairies in Texas and the majority are small herds. DSHS conducts routine testing of the raw milk for somatic cell count, standard plate count, coliform, antibiotics, added water and six common pathogens every three months. We have started testing raw milk from retail raw dairies that are near (in the same county or in a county adjacent to) a known outbreak of avian flu in commercial producer dairies. We are following USDA’s surveillance plan, which entails testing the retail raw milk three weeks in a row to confirm HPAI is not present. DSHS is also looking into the state lab’s ability to do additional testing if it becomes necessary in the future.
There have been no confirmed cases of H5N1 in dairy cattle in Utah. Currently, there are no restrictions on the sale of raw milk in Utah related to H5N1. UDAF will maintain our existing testing requirements for all dairy products, including raw milk. Though UDAF doesn’t specifically test for H5N1 in raw milk, if somatic cell counts exceed 400k, samples will be sent to a lab at Utah State University for additional testing. UDAF supports the FDA’s recommendations and continues to advise individuals who choose to consume raw milk and raw milk products to heat these products to 165° for at least 15 seconds before consuming to reduce health risks associated with raw milk and raw milk products.
“The Minnesota Department of Agriculture (MDA) is working with our partners at the Minnesota Board of Animal Health, Minnesota Department of Health, University of Minnesota Extension, and the dairy industry regarding a Minnesota dairy herd testing positive for H5N1 highly pathogenic avian influenza, and is providing any needed assistance to our dairy producers and workers.
While producers routinely isolate sick cows and divert milk away from the food chain, we know pasteurized milk products are safe to consume, and pasteurization effectively inactivates bacteria and viruses in milk.
Because state law allows consumers to purchase raw or unpasteurized milk in limited circumstances, the MDA advises dairy producers to follow state and federal protocols for sick animals and encourages producers to test sick cows. Consumers who choose to purchase unpasteurized milk should discuss biosecurity and testing measures with the dairy farmer.”
Dr. Nicole Neeser, MDA’s director of our Dairy and Meat Inspection Division:
“Minnesota law restricts sales of raw milk direct to consumers from farms on an occasional basis. Herds affected with the virus are not allowed to sell raw milk direct to consumers because that milk is likely to contain harmful pathogens. The MDA also continues to advise dairy producers to follow state and federal protocols for sick animals and encourages producers to test sick cows. Consumers who choose to purchase unpasteurized milk from unaffected farms should discuss biosecurity and testing measures with the dairy farmer.”
The New Mexico Department of Agriculture continues to be in communication with the state’s retail raw milk producers and their veterinarians to monitor herd health.
The sale of raw milk to the consumer is illegal in the state of Ohio. Any raw milk leaving Ohio licensed dairy farms goes for further processing to regulated facilities with proper pasteurization, proved to effectively inactivate the virus.
The New Hampshire Department of Health and Human Services (DHHS) does not recommend the consumption of raw milk. However, there are no current plans to restrict the sale of raw milk in New Hampshire, which is permitted under state law.
Pasteurization, which kills harmful germs that can cause illness, is crucial for milk safety. FDA testing has confirmed that pasteurization inactivates the H5N1 virus, and pasteurized dairy products remain the safest way for consumers to enjoy the benefits of milk. While DHHS is working with partners to assess the feasibility of testing raw milk samples, there are no immediate plans to do so.
DHHS continues to closely monitor for any H5N1-related developments that may impact public health in partnership with state agencies, including the Department of Agriculture, Markets, and Food, and federal agencies.
“The Massachusetts Department of Agricultural Resources is proactively monitoring the situation for Highly Pathogenic Avian Influenza in dairy cattle, urging local farmers to implement strict biosecurity measures. Working in collaboration with the Department of Public Health, we are conducting voluntary testing among dairy farmers to detect the virus and ensure the safety and confidence in the milk supply. While there are no current plans for the Department to impose restrictions on the sale of raw milk, we will continue to align our decisions with scientific evidence, data, and the guidance provided by the FDA and USDA.”
Retail sales of raw milk in Michigan is illegal. It is not sold in stores or other commercial settings. Consumers may currently only obtain raw milk if they are members of a herd-share agreement and they go directly to the farm to pick them up.
The Michigan departments of Agriculture and Rural Development and Health and Human Services continue to highlight the importance of only consuming pasteurized milk products.
There were no interstate movements for that Benton County, Minnesota herd.
Connecticut Department of Agriculture is working closely with local, state, and federal partners to monitor the emerging H5N1 in dairy cattle issue to ensure the health of animals and the public, safeguard the state’s milk supply, and protect the wellbeing of farmworkers. Intrastate sales of raw milk are allowed in Connecticut. Producers of raw milk and raw milk cheese must register with Connecticut Department of Agriculture to obtain a permit to operate and undergo routine testing. We will continue to monitor the H5N1 situation and adjust as needed.
No, the testing methods USDA has implemented in response to the detection of H5N1 in dairy cattle are not ineffective. As USDA has previously iterated since the implementation of the Federal Order, and as it underscored during its recent announcement on next steps to ensure the health and safety of the nation’s livestock and poultry: as additional testing measures take place, USDA anticipates that it will see an increase in testing and positive test results, which will add to our knowledge of the disease and how it may spread between herds. USDA is encouraging testing in every way possible and is providing more ways to do so, in addition to the Federal Order; this has led to an increase in producer confidence and the recognition of the importance of testing symptomatic herds and consequentially, the occurrence of more testing and therefore more positive cases. This shows that, in fact, our testing methods are working. More pertinently to your question: we are still conducting epidemiological work on the new detections in new states, but at this time we do not believe those cases are a result of interstate cattle movements.
In addition to testing, biosecurity is the key to containing this virus, and ultimately ensuring that it is eradicated so that producers do not have to deal with this virus in dairy cattle permanently. Good biosecurity – including cleaning and disinfection of vehicle and equipment – is critical to minimizing the risk of disease spread. USDA works closely with state animal health official, producers, and industry organizations to provide guidance and resources for cleaning and disinfection not only on affected farms but for all livestock producers as a part of practicing good biosecurity. APHIS has made available a number of biosecurity documents on its landing page: https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/livestock.
Todd Davis, CDC [00:22:26]
The second human case that was identified from Michigan did have a relatively high CT value in the nasopharyngeal specimen that was collected from this individual. We were not able to isolate virus from that specimen. And we were only able to generate a partial HA, a full length neuraminidase, nd no internal gene sequences, from this case to date.
So we’ve just recently, in fact, Monday of this week, posted the partial HA and full length neuraminidase sequences in both the GISAID and NCBI databases. So that data is now available publicly.
But I’ll mention that, you know, we also saw no amino acid changes in the HA of the second case from Michigan, relative to the first case from Michigan and the Texas virus. And so we see no changes that have been associated with receptor binding domain mutations that would impact infectivity or transmissibility among humans. We see no changes in angenic sites that would be expected to impact the candidate vaccine virus cross protection.
So still no changes of note in the hemagglutinin gene of these viruses. And in addition, the neuraminidase sequence also confirmed that there were no changes associated with reduced susceptibility.
Thanks for reaching out. Raw milk sales for human consumption are illegal in Nevada. For questions on raw milk, I recommend you reach out to California, Idaho, or Arizona agriculture departments, as they allow its sale. The NDA is testing dairy cattle according to the requirements for cattle movement. There have been no reported cases of H5N1 in Nevada.
Are there any plans to conduct surveillance of raw milk for H5N1?
DHEC’s Dairy program is working closely with the State Veterinarian at Clemson Animal Health to determine what, if any, surveillance may be necessary. Currently there have been no indications of any dairy cattle illness in South Carolina and no cattle from infected herds in other states have been imported into South Carolina.
Are there any plans for restrictions on raw milk sales due to the outbreak?
No; however, the Raw Milk for Human Consumption regulation requires that raw milk from ill cattle may not be sold, so if H5N1 was diagnosed in a milking cow at a permitted farm, that farm would be restricted from selling raw milk until then herd was cleared by the State Veterinarian.
People who work with or consume raw milk should be aware that there are potential health risks associated with the raw milk, including H5N1. All labels on raw milk for human consumption products in South Carolina are required to feature the following consumer advisory: “This is a raw milk product that is not pasteurized. Consuming raw milk products increases your risk of food borne illness.”
From: Tin, Alex
Is it known if the infected dairy herd had received cattle from other farms or out of state recently?
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From: Crusan, Michael (BAH)
Great question! A little too early to answer. Whenever we detect a disease we conduct an epidemiological interview with the producer to determine recent animal movements or risk factors for disease to have been introduced. That is in process at the moment and our field veterinarians are meeting with the affected herd this afternoon.
Jay Butler, CDC [00:10:01]
Very recently, a second case was identified in Michigan associated again with exposure to cattle on a different farm than the first first case in Michigan.
This case was a little different because in addition to reporting burning eyes, this individual reported runny nose, sore throat, and a bit of cough. Again, the recovery was fairly rapid.
And I wanted to stress that in each of these instances, there has been no documentation of human to human transmission.
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Jay Butler, CDC [00:11:40]
So working with state and local health departments, we’ve been monitoring people who’ve been exposed to cattle for 10 days after exposure. I will be upfront to say the amount of follow up has been variable among the states that have been involved.
But so far, nearly 400 people have been monitored from the affected farms. People who develop any symptoms are tested, and we have the three cases that have been confirmed.
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Jay Butler, CDC [00:13:59]
This involves increasing the number of influenza virus specimens that are tested and subtyped to determine if they’re H5N1 in public health laboratories across the U.S. We want to increase outreach to healthcare providers, which is one of the reasons we’re having this discussion today to raise awareness so that patients with conjunctivitis or respiratory illness are screened and tested for novel influenza, if indicated.
And finally the approach will maintain increased level of testing during the summer months when seasonal influenza activity is typically low and therefore testing decreases.
What will happen in the fall when we begin to see seasonal influenza? That’s still a few months off and it’ll depend on how things evolve over the next couple of months.
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Jay Butler, CDC [00:16:54]
We’ve sequenced the influenza virus from the conjunctival specimen collected from the first case in Michigan.
Attempts to sequence the virus in the clinical specimen from the second case in Michigan are underway, but are challenging because the CT values are high, suggesting a low viral load.
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Jay Butler, CDC [00:59:48]
A rapid influenza test likely would be positive. There is some evidence though that sensitivity is reduced with H5N1.
And the important context for that is to realize that the rapid tests sometimes struggle with sensitivity to begin with. So if there is a high index of suspicion, getting a specimen that can get to a lab to perform nucleic acid testing, I think is an important step in making the diagnosis.
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Jay Butler, CDC [01:03:19]
I think it comes down to the relationship that we have between health and the workers, particularly government public health, or really any government agency. A number of the workers are immigrants. I can’t say how many are documented, how many are undocumented, but there’s certainly some resistance to having any kind of intervention that might potentially cause problems for the individuals that are being asked to participate in studies or in investigations.
I think just like in clinical medicine, having a relationship with the patient is critical, same thing in public health. Having a relationship with the population is really critical.
Some states have been able to really move forward in establishing that relationship. Real shout out to my public health colleagues in Michigan who have been able to be more aggressive in testing individuals that have been exposed to infected cattle.
The dairy reached out to us earlier this week reporting symptomatic cattle. We helped to coordinate testing. Iowa State Veterinary Diagnostic Laboratory detected the virus. NVSL has since confirmed them.
On February 20, 2024, the PA Dept. of Agriculture’s Bureau of Food Safety received a consumer complaint that “apricot kernels” were available for sale at Sonnewald Natural Foods in Spring Grove, York County Pennsylvania. Apricot kernels are known to contain amygdalin, which converts to cyanide in the body.
Department food safety inspectors visited the store on February 22 and photographed products on the store shelves, forwarding photos to the FDA and also alerting the Texas Department of Agriculture. Since the manufacturer is located in Texas, the investigation and testing that resulted in the FDA warning were led by Texas.
FDA officials indicated that the product was mislabeled, and PA officials had the products removed from the shelves, in advance of the test results.
The department is not aware of any other Pennsylvania locations carrying the products or of any consumers who have been sickened by the products.
Cody Meissner, VRBPAC [09:30:10]
If the composition of the vaccine differs between the recommendation from, for example, the WHO and our recommendation today, what, how complex a problem is that for the pharmaceutical manufacturers and can they, could they deal with such a situation? It may not be a question to answer right now, but hopefully the manufacturers can address that as we move forward. Thank you.
Jerry Weir, FDA
So I will give you the short answer, but you’re right. The manufacturers are best suited to answer it specifically.
What you will hear though later today is most manufacturers have already done some at risk work, to try to be prepared for various choices. Obviously no one can be prepared for all the possible choices, but you’ll hear that.
And you’ll hear from each of the manufacturers about how the choice affects their particular timeline. And it’s true that different manufacturing technologies may be affected more than other ones, depending on the choice.
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Peter Marks, FDA [09:32:02]
The manufacturers, we have seen the issue of having a potential JN.1 versus KP.2, discussion or KP variants now, other KP subvariants, coming for a while.
The manufacturers think are very well prepared to speak to their ability to address this. I would just encourage again, the committee today to focus on what makes the most sense from a scientific point of view. Because I think that as you’ll hear from the manufacturers themselves, they have done the pre-work to ensure that they are most able to follow what is most appropriate from the scientific and medical standpoint.
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Natalie Thornburg, CDC [09:44:32]
So we saw XBB.1.5 lineage viruses circulate through the summer last year and into November. And then in December much like December of 2022, we saw a strain replacement. This time the string replacement was JN.1 lik.
So again, like when we saw BA.5 to XBB.1.5, that was a shift, it was from a different phylogenetic lineage, the same thing occurred this winter, with that shift in JN.1-like viruses, and then much like last year, we have seen a parental lineage circulating in the early winter, and then we start to see diversification in the spring, which is what we’re seeing now.
And so you can see pink, some gray, some KQ.1 like, some KP.2 like, that is, some diversification that we are currently observing much like we did last late spring, early summer.
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Natalie Thornburg, CDC [00:46:44]
There’s a particular amount of uncertainty right now because we have a lower number of sequences in the weighted estimates than we have historically. And that’s due to a combination of factors: testing practices, availability of specimens, because there’s not a lot of community transmission, there just aren’t lot of specimens to then sequence, and just, you know, limited laboratory capacities throughout the entire country, um, to maintain the level of sequencing that was maintained two or three years ago.
But we still feel we still feel fairly confident in lineages that are increasing and decreasing. The biggest might sort of ride one edge of those confidence intervals.
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Natalie Thornburg, CDC [00:23:46]
So, KP.2 and similar viruses are currently the most prevalent viruses in the United States. So there are several groups of viruses that actually have the same spike sequence. So I’m calling them KP.2 like viruses, and that includes KP.2, JN.1.16.1, and a few more. So those are the most prevalent circulating viruses, KP.2 and KP.2 like viruses.
And the second most prevalent viruses that we’re predicting our KP.3 lineage viruses. Both of those sets of lineages are descendants from JN.1 and are very similar to JN.1. And I will show you that in a moment. But KP.2 and KP.3 lineages have evolved independently of each other, but both from JN.1.
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Natalie Thornburg, CDC [00:25:52]
So, this is a summary of substitutions that are in the receptor binding domain for the most important part of this spike protein in comparison to XBB.1.5, the current vaccine formulation. I want you to look mostly on the bottom half of this table, where you see the most sort of substitutions pop up is the JN.1, that strain substitution. There were quite a lot of substitutions in the receptor binding domain and throughout the rest of spike protein in comparison to the vaccine strain.
But then if you look at the bottom two rows, KP.2 like viruses, those, the lineages that all have the same spike protein, the different names, and KP.3, the bolded lineages means that right now we are predicting that they’re increasing in proportion.
And what I want you to notice is they’re very, very similar to JN.1. There’s not a lot of differences. We’re really talking about two differences in receptor binding domain. And when you look at KP.2 and KP.3, they’re nearly identical to each other with really one difference between the two of them.
So it’s two differences for each of those in comparison to JN.1, and one difference between KP.2 and KP.3.
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Natalie Thornburg, CDC [00:28:15]
So the take home method I want you to see in this one is that the JN.1 viruses they’re kinda all clustered together, on the right side, kind of a quarter of of the way or a third way up, up the Y axis.
So, and JN.1, KP.2 like viruses, they’re really, really on top of each other. And KP.3 is very close by not absolutely on top of it, but very, very close by. And they cluster away from XBB.1.5 viruses. And that is sort of like down into the left a little bit, those are the XBB.1.5 cluster viruses.
So JN.1 descendant viruses, including KP.2 and KP.3 are antigenically technically similar, using this particular mouse model.
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Natalie Thornburg, CDC [00:30:04]
So the current circulation of SARS-CoV-2 is relatively low. JN lineages have replaced XBB.1.5 lineages during the winter of 2023 and 2024.
The severity of JN.1 infections do not appear to be worse than earlier XBB.1.5 infections. JN.1 lineages are currently undergoing phylogenetic diversification. We’re seeing convergent evolution of the spike occurring. So we’re seeing similar substitutions in the spike, similar substitutions in different lineages of viruses, and KP.2 like lineages and KP.3 like lineages are currently predicted to increasing in proportion.
Both of these lineages only have two substitution in the spike receptor binding domain in comparison to JN.1. And preliminary data indicate that JN.1 lineages are antigenically similar.
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David Wentworth, CDC [10:48:11]
It’s really challenging, right? Because I think the key is to have antisera to those viruses. And ideally you want human antisera to those viruses to better understand exactly what would happen.
And as Dr Perlman mentioned, really the vast majority of the response is driven by cross reactive B cell memory responses that are to the new antigen. They’re not all to the old antigen. There are things that cross-react with the new antigen.
And JN.1, we do have data for that from both animal models and humans. Whereas as a committee, we didn’t have any data on KP.2. And what I was trying to get at with that fake cartography was, KP.2 may be better, but it could also be worse, right?
And the reason it could be worse is multifactorial. It couldn’t– it could not create as high a titer when you immunize that’s one of the issues, right? Or it creates a very mono specific titer where it really neutralizes KP.2 well, but it doesn’t neutralize other variants as well. And this we saw with XBB.1.5 had a broader cross reactivity pattern than XBB.1, for example, last year. And part of the reason XBB.1.5 was kind of narrowed down as the monovalent recommended by the WHO committee.
So kind of looking at the prior history, the limited history we have, that’s the challenge.
And whether or not you have artificial intelligence, there are efforts in that space, but you really need the data to help inform either the human intelligence or the artificial intelligence, which is antisera to those newest variants, which when you have a variant like KP.3, that just popped up, it takes a month to make antisera.
So we’re always going to be in that situation of only knowing what we know now. And I would just finalize by saying we’ve really seen KP.3 increase a lot. And that 493 substitution from a glutamine to a glutamic acid is probably more impactful than the 456L substitution.
So that would– I would want to make sure we could the serum neutralizes within fourfold the variants that I know are important, which are KP.2 and KP.3
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Darin Edwards, Moderna [11:15:04]
In summary, our preclinical results suggest that both a JN.1 and a KP.2 new variant vaccine cross neutralizes JN.1, KP.2, KP.3, and other currently circulating JN sub variants.
Based on the FDA’s recommendation, Moderna is prepared to submit a JN.1 or KP.2 new variant vaccine dossier for approval and is ready to supply the U.S. market with either vaccine composition by mid-August.
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Sarah Meyer, CDC [11:19:38]
It looks like the antibody titers after JN.1 are a little bit higher than after KP.2 vaccination, but they’re very similar. So I just want to confirm, is your interpretation of the data that they equally perform, or do you think that they, there is some slight advantage to the JN.1 vaccine? So that’s my first question.
Darin Edwards, Moderna [11:20:01]
Yeah, no, thank you for that question. I’m actually showing back the JN.1 data and then in just a second, I’ll share the KP.2 once again. That is our interpretation. It’s very difficult to see significant differences in the performance of either the JN.1 or the KP.2 vaccine in this type of model, this boosting model, this model of boosting with these updated vaccines. So yes, I do confirm that’s our interpretation.
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Sarah Meyer, CDC [11:20:40]
My question for that is the kind of volume or doses available at the start, because I think from a program perspective, it’s helpful to have as much supply available at the start. I mean, people are seeking the vaccination versus like a trickle out over time. So my question is for either of those vaccines, would you expect a difference in terms of the amount of vaccine available in mid-August, and kind of, if there’s any differences, what would be the magnitude of that?
Darin Edwards, Moderna [11:21:09]
So we are still in negotiations with some key retailers and pharmacy chains, for contracts for the fall. That said our projections are that either vaccine, we will have sufficient supply to supply, not only at the initiation of vaccination campaigns, but throughout the season for either vaccine composition.
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Kayvon Modjarrad, Pfizer [11:38:09]
The KP.2 vaccine, like the JN.1 vaccine, elicited a similar breath of neutralizing activity against all JN.1 sub lineages. We compared the magnitude of responses of the JN.1 and KP.2 vaccines relative to the XBB.1.5 vaccine.
Whereas the JN.1 vaccine elicited two to fold higher responses than the XBB.1.5 vaccine, similar to that observed in the prior vaccine experience study, the KP.2 vaccine elicited between three and sevenfold higher responses against this broadly representative panel of JN.1 sub lineages.
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Kayvon Modjarrad, Pfizer [11:39:20]
JN.1 and KP.2 adaptive vaccines confer improved neutralizing responses over XBB.1.5 vaccine against a broad panel of emerging variants.
Finally, we are prepared to initiate supply of either JN.1 vaccine or KP.2 vaccine immediately upon approval, and we continue to work to meet public health needs in protecting against COVID 19 as per the committee’s recommendation.
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Robert Walker, Novavax [12:00:09]
Selecting a vaccine strain that is antigenically similar to a broad range of circulating strains, and not necessarily the currently dominating strain, may be an approach to de-risk the selection process.
Our vaccine also induces a conserved polyfunctional TH one biased T-cell response against JN.1 lineage sub variant viruses. Our data support a JN.1 lineage vaccine update for the 2024 2025 season aligned with WHO and EMA recommendations.
Our recommendation from this committee for a JN.1 vaccine will enable a protein based based vaccine option to be available to the U.S. population this fall. If the recommendation precludes use of a JN.1 vaccine, then a protein based option will not be available in the U.S. for the fall vaccination effort.
Finally, commercial manufacturing is ongoing and initial shipments of JN.1 vaccine are on track to be in U.S. warehouses in August.
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Robert Walker, Novavax [12:04:33]
We are currently manufacturing JN.1 vaccine. That’s correct.
So, in order to have a protein vaccine ready to go, September 1, we’re prepared to provide the JN.1 vaccine. We think, based on the data I’ve shown you today, that the JN.1 vaccine is appropriate and has good cross neutralizing activity against all the subvariants that are currently circulating.
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Jerry Weir, FDA [12:28:45]
A couple obsewrvations about the future directions of this process.
I think we’ve all resigned ourself to the fact that updating the SARS-CoV-2 strain composition for vaccines is going to be a continuous process. But I think we’ve also, it’s becoming clear that the ideal timing for a vaccine composition decision remains elusive.
The virus continues to evolve without a well defined seasonality, vaccine production timelines differ depending on the manufacturing technology, and there is still uncertainty regarding the optimal timing for vaccine administration.
In other words, trade offs are inevitable in the timing of the vaccine composition decision.
And finally, I want to mention that this process, there’s still many challenges that remain. And I think Dr. Wentworth mentioned some of these too, but I’ll highlight them again.
At the time we make these decisions, there is a limited amount of critical nonclinical and clinical data available at the time we must make the recommendation.
We still poorly understand how the differences in neutralization titer relate to clinical outcomes. The current non-clinical models, the animal models that we’re using imperfectly reflect the human populations receiving the vaccine. And human post vaccination and post-infection serology panels are simply not available for distinct populations, such as pediatric adults, elderly who may respond differently to vaccination or infection.
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Bill Falstich, Pfizer [01:58:38]
We have modeled demand based on our prior experience, based on our negotiations with customers and discussions with customers. And then based on analogs, such as flu uptake.
We project that based on the demand we have modeled, we’ll be able to supply in all periods, starting as early as August or upon approval. We’re preparing for an August approval, but of course that’s subject to regulatory review and timelines.
And we would maintain that supply for as long as it’s needed. So through the end of the year and then into the 2025 season as well, is what we would anticipate doing.
Arnold Monto, VRBPAC
And Novavax? Please, go ahead.
Robert Walker, Novavax
As mentioned during the presentation, we are manufacturing JN.1 vaccine.
We anticipate no constraints, that we would be able to meet to projected demand. And, we are projecting to have that available, as mentioned, September 1.
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Ruth Link Gelles, CDC [02:11:37]
It’s very difficult to talk about timing COVID 19 vaccines for the respiratory virus season.
For flu and for RSV, we have years and years of data with very similar trends over time. So, you know, you can’t quite set your watch by when those seasons are gonna start, but you can do– you can get close.
For COVID, that’s not true at all. We’ve seen surges in the summer, in August, the last few years. And so I think it becomes a little bit of a difficult game to try to play to time COVID vaccine introduction at the same time, right before a surge.
I think the other important point to keep in mind is that when we’ve seen COVID surges before, they’re often, you know, with quite a peak, rather than sort of a large span of time. And so to put in place a recommendation of roll out vaccine and get people vaccinated in time, and then they need about a week to two weeks to really have the full benefit of the vaccine, we would risk kind of missing that peak.
And so I, for those two reasons, I think it’s very difficult to try to time COVID vaccine before an oncoming surge. And so I think what we’re left with is trying to time it with a respiratory virus season, and think about uptake at the same time as folks are getting their flu vaccines.
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Jerry Weir, FDA [02:15:13]
Our ability to review and act on it will depend on when all of the necessary data is submitted and the manufacturers may or may not be able to submit the same amount and quality of data for one variant as another, at exactly the same time.
That’s what I meant about, you might have to ask them when they would be able to submit data to the FDA, but that would be the only limiting factor, but it would be relatively minor in the scheme of things as far as timing.
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Designated Federal Officer [02:49:39]
So out of these 16 total voting members for today’s meeting, we have 16 yes votes and zero no votes.
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Peter Marks, FDA [02:57:07]
I’m just a little concerned that perhaps the committee doesn’t understand that if they choose to recommend or to make any comments about a KP.2 vaccine, that does not mean that there will not be availability of a JN.1 Novavax vaccine necessarily. It just may mean that there will be two different formulations available.
Now you might say, how could that be? But that’s precisely what happened two years ago, when Novavax had their original vaccine available, when we had bivalent available, and yes, there was some preference given towards an updated vaccine.
I guess we could consider how we would word this now, but I do– I would ask for the committee to comment a little bit on this concept. We’re saying we will settle for JN.1. But I’d just kind of like to understand from a scientific standpoint, do we think there’s some possibility that that KP.2 or KP.3 are potentially going to evolve back closer to JN.1, because all of the data seem to show that neutralization, and granted we’re not saying that that’s a big deal here except perhaps, in newly vaccinated individuals, if you look closely at that, do we really think that that we’re– are we really okay with this?
And if this evolves further in the fall, will we regret not having been a little bit closer? I guess the point here being that, yes, we shouldn’t be chasing– we always say we shouldn’t be chasing strains, but we’re paying an incredibly high premium for mRNA vaccines to be able to have the freshest vaccines.
The analogy that I would make here is that, at least for me, when I go to the milk case to buy milk, despite the fact that all the milk I buy is ultra pasturized and it’s never going to go bad before I use it, I always tend to buy the most recent dating rather than an older dating. And that’s just in case.
So the question, I just would love the committee to comment a little bit more about this, knowing the full well that we might have a solution for the Novavax issue that we’re not going to, our intention is not to take away choice, but it’s to just accept that this is the nature of mRNA versus protein based vaccines over.
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Arnold Monto, VRBPAC [03:01:38]
One of the things that may be troubling a single choice is the schematic, which showed JN.1 in the middle, and KP.2 in one direction and KP.3 in the other direction.
So, it becomes a little bit of a problem trying to come up with a unitary choice.
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Peter Marks, FDA [03:25:39]
Thanks to all the members. Really appreciate the feedback today. It actually was very helpful.
This was a good check.
We wanted to make sure that we gave people the option to potentially make a choice of a KP.2 vaccine. We hear loud and clear from all of the members that they don’t feel like that is necessary at this time. That a JN.1 vaccine for all is acceptable. We take that back.
We really appreciate your feedback in that regard.
Today was an important day as the FDA Advisory Committee panel discussed MDMA-assisted therapy for PTSD. This meeting was unprecedented in many ways including that it is atypical for an Advisory Committee to review an application that combines a drug and psychological intervention. In addition, this would be the first psychedelic-assisted therapy, if approved. While we are disappointed in the vote, we are committed to continuing to collaborate with the FDA with their ongoing review of our NDA over the coming weeks. It is important to note that the FDA is not bound by PDAC’s guidance but takes its advice into consideration. Today’s discussion made clear that there is an urgent need for new, effective and accessible therapies to address this unmet need for those living with PTSD. We are in ongoing discussions with the FDA about a risk evaluation and mitigation strategy (REMS) program, however, that has not yet been fully defined. Part of the purpose of the meeting today was to help inform this REMS program so we can continue to collaborate with the FDA to define the key elements. We will also work with the FDA to determine the most appropriate post-marketing plans to address the outstanding questions raised today, including how best to support the responsible integration of MDMA-assisted therapy into the healthcare system. If FDA-approved, prescription MDMA-assisted therapy will be launched with careful consideration of its potential benefits and risks, in accordance with established medical guidelines, protocols and quality standards.
Amy Laverdiere, Lykos Therapeutics [09:24:54]
MDMA is not a new drug, and while it can misunderstood due to its illicit counterpart, it actually has a well documented history in the psychiatric field.
In the 1970s and early 1980s, MDMA was used in conjunction with talk therapy by mental health providers since research suggested MDMA allowed patients with psychiatric disorders to access, process and communicate difficult emotions and experiences.
It’s been documented about 4,000 people have been administered MDMA in earlier clinical practice. In addition, about 2,000 participants have been included in more recent research studies. This historical experience along with an extensive library of published literature, informs the design of our clinical program.
MDMA-AT has been studied across 17 clinical trials. Throughout clinical development, we’ve worked in collaboration with the FDA. A special protocol assessment for our two nearly identical pivotal studies, MAPP 1 and MAPP 2, was agreed in 2017.
Due to the seriousness of PTSD and the encouraging preliminary phase two data, MDMA-AT received breakthrough therapy drug designation that same year and the NDA was submitted in 2023 and granted priorly review.
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Amy Laverdiere, Lykos Therapeutics [09:13:40]
MDMA is entactogen that has the potential to be a powerful disease modifier. While the specific mechanisms are not completely understood, this in the brain, MDMA is thought to be monoamine reuptake inhibitor and releaser.
We know psychotherapy can be effective, but only if patients are able to tolerate the treatment. The available data and mechanism of action suggest that MDMA catalyzes the effectiveness of psychotherapy by facilitating memory recollection and extending the patient’s window of tolerance for revisiting distressing thoughts or experiences.
Studies with MDMA show improved self awareness and prosocial effects that enhance the therapeutic alliance between the patient and their therapist. By leveraging the effects of MDMA, individuals are more open to the potential benefits of psychotherapy. This psychological intervention includes aspects of established therapeutic approaches.
This combination of MDMA plus psychological intervention provides patients with an acute treatment to reduce the symptoms associated with PTSD.
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Dr Alia Lilienstein, Lykos Therapeutics [09:36:54]
MDMA has a moderately high potential for abuse. Importantly, however, illicit MDMA use is known to be primarily episodic and rarely results in substance use disorders.
That is likely because MDMA is primarily serotonergic in action and it’s unlikely produce physical dependence or withdrawal syndrome. This distinguishes it from typical psychostimulants, which primarily activates the dopamine system.
The morbidity and mortality associated with illicit MDMA is considerably lower than methamphetamines, similar to amphetamines, and higher than methylphenidate.
While use of illicit MDMA cannot be completely prevented, approval of a controlled product provides the opportunity to regulate and monitor the field to a greater extent than what is currently possible.
We’re working with FDA to develop a REMS program, to evaluate and mitigate the risk of serious harm resulting from patient impairment. According to the proposed REMS, MDMA will only be dispensed in certified healthcare settings, and only with evidence of safe use conditions.
This includes training for prescribers, pharmacists and therapists, and patients will be counseled to support safe use.
Patients will be monitored during and after the session and will be required to be enrolled in midomefetamine drug registry.
Beyond the REMS, we’re working with agency to develop a comprehensive plan to mitigate risk and translate the positive benefit risk of MDMA assisted therapy observed in the clinical trial setting to clinical care post approval.
The mitigation efforts address each of the identified or potential risks. They include patient monitoring, appropriate labeling, prescriber educating, including appropriate selection of patients, and therapist training on patient monitoring for these risks.
We also have additional efforts to support use in clinical practice. We plan to initially work with a limited number of sites that take specific steps to put the staff and processes in place to effectively and safely deliver MDMA assisted therapy.
The basic premise of this treatment approach is that the psychological component is important. To support MDMA use in clinical practice, we will provide training for therapists on the treatment approach used in the phase three clinical trials.
Furthermore, the medication for this acute treatment will be supplied in single dose packaging, further limiting nonmedical use and medication errors.
To conclude, overall, three total doses of MDMA were well tolerated. The adverse events were consistent with the known safety profile of MDMA, with mostly mild to moderate and transient adverse events. No patients assigned MDMA died or experienced a serious adverse event in our pivotal studies.
In addition, the risk can be appropriately managed and mitigated with proposed labeling and REMS.
The favorable safety profile observed in the clinical program will translate to practice if approved due the inherent safeguards of an acute treatment with controlled distribution.
Lastly, we agree with the agency that additional postmarketing studies such as laboratory safety data collection can further inform patients and providers while the benefit risk of this treatment is well characterized our clinical development program.
We recognize more can be learned in a real world setting. We acknowledge the need to move forward with care and caution to bring this new tool to patients suffering from this serious and life-threatening condition.
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Dr Kelley O’Donnell, NYU Langone (for Lykos Therapeutics) [09:41:39]
This treatment is under a lot scrutiny right now. PTSD patients are a genuinely vulnerable population and some of the strengths of MDMA may also represent challenges moving forward.
Careful screening, education, and monitoring patients and rigorous training of licensed providers will be essential for mitigating those risks.
But the complexity of this treatment, like the complexity of the PTSD population, should not preclude approval because it’s clear that MDMA assisted therapy would be a welcome addition to the available options.
I’ve seen first hand how the intensive treatment can be lifesaving for some, including some who haven’t benefited from conventional approaches at all.
This need is, of course, all the more urgent, because despite the seriousness of this disease, we haven’t seen a new pharmacologic intervention for PTSD in decades.
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Question [10:30:31]
So there was a recent, fairly high profile ICER review, with claims that there was a misconduct during the clinical trials. Lykos responded really quickly to that, with a public letter.
My question is number one, when was Lykos first made aware of these allegations and number two, what steps did Lykos take to investigate and rule out these occurred? Because your letter indicated there was any denial of such conduct.
Did you do an internal investigation? Did you hire a third party often to come into investigate? Can you can speak to that?
Dr Alia Lilienstein, Lykos Therapeutics
The company was initially made aware of this event in late 2018. And an investigation was undertaken internally in the company, to both understand what had happened and improve any processes within the company to prevent this in the future.
It’s never okay for a care provider to cross boundaries. It’s unethical behavior, and it’s malpractice.
We work with licensed healthcare providers now, only, and they’re trained, in addition through our therapy training program, to understand how the drug may impact boundary setting for patients and to reinforce upholding boundaries on their part as well.
Question
So in addition to the boundary violations, I think that is going to be a big part of the conversation later on, but there were these allegations that some folks, subjects, were discouraged from participating in MPLONG, and based on your briefing document, it appears that patients either were enrolled in MPLONG or by themselves decided not to.
There was no suggestion that they were excluded by the principal investigators, but again, allegations from the ICER review, suggesting again, unsubstantiated claims of subjects stating that they were discouraged from participating in MPLONG study.
Were those things investigated?
Dr Alia Lilienstein, Lykos Therapeutics
Yes, those were investigated as well.
And all participants who were interested in participating were given the opportunity to review consent and some chose not to participate, after reviewing consent, but otherwise everyone was given the opportunity.
Question
Okay. So my understanding is that no subjects were excluded based off of one of the second criteria, which was, if there were any problems that the principal investigator identified, that would make participation in MPLONG problematic?
Dr Alia Lilienstein, Lykos Therapeutics
There was at least one participant I’m aware of who, because they were doing so poorly, felt like that participation in the study would be really negatively impacting for them, but they were– a conversation was had.
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Question [09:55:15]
The first is related to the controlled distribution pathway, and I think I want a little bit more detail on if I’m a patient, how am I obtaining the medicine or controlled substance, and then how is it being administered? So that’s the first question walking me through that controlled distribution pathway.
And then the second is under the mitigation strategies. There was a mention of limited rollout. And so can you walk me through what limited rollout means and what metrics of success you would use to then expand access, please? Thank you.
Amy Laverdiere, Lykos Therapeutics
Based on the parameters of the proposed REMS, which we’re still developing with input from FDA, the dispensation would only take place in certified healthcare settings that also have demonstrated evidence of safe use conditions.
So by controlled distribution, what we mean is that there would be a limited number of pharmacies. They would either have to be on site at the certified healthcare setting, or similar type of distribution approach.
There are additional restrictions on compounds that are dependent on their ultimate scheduling by DEA. So there’s still some details that need to be worked out in terms of what is completely compliant with both FDA expectations and DEA regulations, and that’s something we’re actively engaged on working on with both FDA and DEA.
So it’s something that will follow all the requirements that apply, depending on how the scheduling goes.
In terms of how the product is administered, this would only be administered in these certified healthcare settings that have the appropriate personnel and plans in place to conduct the patient monitoring, deliver the psychological intervention, and also have plans in place for medical escalation.
And, in terms of the limited rollout, what we intended is that we would start out with a smaller number of commercial sites that were able to meet the requirements of this certified healthcare setting, safety conditions, in order to essentially pilot what our risk mitigation procedures are able to detect and submit reports to the agency for those REMS assessments on the required schedule.
The metrics for how we would expand on patient access are something that we’re also still developing. However, we strongly believe that patient access is very important. And as a result, we’re envisioning this as a staged rollout.
So although we may start with limited number of sites initially, after demonstration of appropriate risk mitigation, we would plan to expand from there.
Question
Thank you. So just as a follow up and knowing that the REMS program and logistics still need to be worked out a little bit, but it would be feasible or possible, in the sponsor’s mind that you go to one of these pharmacies, be dispensed one dose, and then take that with you to the therapy session. Is that correct?
Amy Laverdiere, Lykos Therapeutics
The dispensation would have to happen at the certified healthcare setting.
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Dr David Millis, FDA [11:28:25]
However, in reviewing the clinical study reports submitted with the application, we noticed a striking lack of abuse related adverse events.
When we followed up with the applicant about their abuse potential assessment methodology, they clarified that they did not systematically collect abuse related adverse events, as advised in the guidance. Rather, they only documented events characterized as unfavorable. Next slide.
This lack of systematic collection of positive events is a major concern because this is key data that would help us characterize the central nervous system effects of the drug. As a result of not having this data, our ability to properly describe the expected frequency and severity of these events in product labeling is affected.
For instance, although we may be able to include a general description and warnings and precautions of known effects of midomafetamine based on literature, we have no verbatim adverse event terms, so no descriptions of the midomafetamine experience in participant’s own words.
This information could have helped us to determine the best language to describe these effects in the prescribing information. Further, there is no data to quantify the frequency of euphoria or other abuse related events in the adverse reaction section of the labeling.
We also don’t know when participants began to feel the effects of midomafetamine, nor when those effects resolved. This data could help inform recommendations related to appropriate monitoring duration and assessment of discharge readiness after medication sessions.
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Dr David Millis, FDA [11:31:18]
Finally, during our last few meetings with the applicant, we noticed some additional review concerns.
During a breakthrough therapy advice meeting in September 2022, we noted that the safety database for the development program would be considered inadequate if the drug required chronic or chronic intermittent administration to maintain a treatment effect.
This question of durability is relevant here because PTSD is a chronic condition. Any proposed treatment for PTSD should take this factor into account.
The applicant proposed to address this question by providing the results of their exploratory follow up observational study MPLONG, which consisted of a single follow up assessment of participants from MAPP1 and MAPP2, at least six months after the last dosing session.
During the meeting with the applicant, we noted that MPLONG was likely inadequate to fully address the question of durability of effect, but the agency would review the results with an NDA submission. At the pre NDA meeting, the agency noted that a risk evaluation and strategy or REMS would likely be required if this drug were to be approved, but that the specific risks to be mitigated by any proposed REMS would be a matter of review.
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Dr David Millis, FDA [11:34:51]
The three medication sessions lasted at least eight hours a piece. The psychological intervention during the medication sessions consisted of general psychological support, as well as observation for safety purposes. Direct therapy was minimal.
After each dosing session, there were three integrative sessions for a total of nine integrative sessions over the course of the study. The purpose of the integrative sessions was to help the participants describe their experience of the medication sessions, particularly the experience of remembering trauma.
These were the main sessions with a more primary psychotherapeutic interaction occurred.
However, the content or approach of these integrated sessions was not standardized in the treatment manuals, and was mainly left up to the individual therapist. The manual provided general guidelines, orienting the therapist to an appropriate therapeutic stance towards the participants in setting, but not being directive or specific in terms of the content or approach of those therapy sessions.
The approach to therapy was not standardized and could vary considerably, from therapists to therapists. Next slide.
Overall, we know that is difficult then to assess how the psychological intervention provided by the applicant in the studies contributed to the overall treatment effect and results.
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Dr David Millis, FDA [11:36:49]
And as noted already, we do not regulate therapy as a rule, in terms of its specific content or details.
Labeling regulations allow for specification that a drug should be used only in conjunction with another mode of therapy, but that generally requires evidence that the other mode of therapy is necessary to achieve a treatment effect.
Under a REMS, we can require monitoring to ensure a patient’s safety, but a REMS cannot dictate that a patient is offered or engages in psychotherapy.
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Olivia Morgan, FDA [11:50:00]
One limitation of the study is the variable timing of the long term follow up visit one. The visit occurred at least six months, but up to two years, after the last dose in the parent study.
MAPP1 was conducted before MAPP2, and there was a longer lag time between MAPP1 and MPLONG, so the long term follow up assessment was generally later for those participants. Next slide.
Another limitation of MPLONG is that some participants reported using non study drug interventions in the interim period between the parent study and MPLONG. Participants from MAPP 1 and MAPP 2 reported using ketamine, the psychedelic MEO DMT, or illicit MDMA.
The number of participants entering MPLONG from MAPP 1 and MAPP 2 who reported use of these psychoactive substances in the interim period between parent study and MPLONG is shown in this table. There were 17 participants in the drug arm and 13 participants in the placebo arm who reported the use of at least one of these psychoactive substances. It is also possible that there may be additional unreported nonstudy drug use in the interim period.
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Dr David Millis, FDA [11:54:19]
Although we do have two positive studies, these results are in the context of dramatic functional unblinding. We know that it is difficult to control the impact of functional unblinding in psychedelic clinical trials. And the applicant did use blinded central raters to attempt to mitigate the impact of unblinding.
Nonetheless, based on the results of the unblinding questionnaire in MAPP 2, it is clear that participants were aware of their treatment assignment, and that could impact their report of symptom control.
As Dr. Farchione noted in her opening comments, a study that is functionally unblinded may still be able to be considered as an adequate and well controlled study. However, the potential influence of bias needs to be factored into the interpretation of the study results.
It is important to consider if there were adequate methods to minimize bias, the magnitude of the treatment effects, the robustness of the study results, and what is known about the natural history of the condition. We also have some exploratory data suggesting that the effects of midomafetamine may be durable, but this is based on a single follow up assessment with a high degree of variability and time to visit.
Further because the applicants who enrolled in MPLONG had fared better in the parent study than those who did not enroll, we have concerns about selection bias. There also remains an unresolved question of the impact of non study drug use between the parent studies and MPLONG.
Finally, the applicant has presented midomafetamine as an aid to psychotherapy. However, the role of psychotherapy and its contribution to the observed treatment response has not been formally evaluated. Also given the inherent flexibility in the therapy manual, there may have been considerable variability in therapeutic approach. However, there were no evaluations comparing whether these changes in therapeutic approach had any influence on efficacy.
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Dr David Millis, FDA [12:08:36]
Our assessment of the rate of abuse potential adverse events remains limited. Thus, although we have enough information based on a review of the published literature and epidemiological data to craft warning language related to abuse potential, and prepare a scheduling recommendation for the DEA, we do not have information about the incidence of particular events that occurred in the clinical trials and will not be able to include those events in the adverse reaction section of labeling.
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Dr David Millis, FDA [12:10:15]
Overall, the safety profile for midomafetamine observed in the development program is consistent with its known effects.
However, certain risks cannot be fully characterized based on the safety data from this program. The assessment of cardiovascular risk, hepatotoxicity and abuse related adverse events did not adequately address these potential risks.
In addition, because abuse related adverse events were not captured, if they were considered positive, favorable, or neutral, we do not have qualitative or quantitative information about the nature of the acute drug effects in this program, or about when those effects resolve.
As a result, we have limited information to determine appropriate discharge criteria for after the medication sessions.
Finally, we have a relatively small safety database in this program. This may be acceptable if we agree that the proposed three dose time limited treatment is effective for the treatment of PTSD and that the treatment effect is durable. But if we determine that additional courses of treatment are needed, the safety database may not be adequate to characterize the risk of chronic or chronic intermittent use.
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Dr Tiffany Farchione, FDA [12:25:47]
There isn’t a lot that I can say with regard to specific details of what we’re looking into related to the ICER report versus just our usual standard inspections.
We’re certainly, I think we’re all aware of the report. We certainly take those allegations very seriously and are quite concerned by them. We do have inspections ongoing at this point, but can’t really speak to the details because those are ongoing.
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Dr Tiffany Farchione, FDA [12:34:23]
Well, I mean, the difficult thing and something that you’ve just hit on very well is that we don’t regulate psychotherapy and also, we don’t really have any say in the design or the implementation of the particular therapy that is going to be used.
We can say generally that this is something that would need to be administered in conjunction with a psychological intervention, but that’s really the extent of what any labeling language would suggest.
And even when it comes to the parameters of the REMS, those are focused on safety and monitoring, not on the intervention that would occur at at the time.
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Question [12:35:48] You mentioned earlier that inspections were ongoing into some of the claims about data manipulation and such. Is it possible if things were to be approved today that it could come out to market before those inspections are completed?
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Dr Tiffany Farchione, FDA [12:36:08]
We would complete the inspections before taking action.
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Dr Tiffany Farchione, FDA [12:41:57]
This is something unprecedented. So we certainly want to get as many opinions and as much input as we can on this product and on our decision making.
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Dr Tiffany Farchione, FDA [12:46:07]
There is not a great answer to that question because again, even if there was a study looking specifically at the psychotherapy itself, that’s not something that would fall under our purview.
So in terms of approving a particular psychotherapy, that’s not something that we would do.
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Dr Tiffany Farchione, FDA [12:49:30]
In the clinical trials, we’ve only required one of the two monitors to have a license. What we have asked for, for the second monitor is, at least a bachelor’s level degree and some experience in a mental health setting and so on. It primarily has to do with the concerns of balancing access as well.
Walter Dunn, PADAC [12:49:59]
So again, reminding folks that that transgression happened with the unlicensed therapist, in the phase two trial, and again, thinking about clinical rollout, I know the sponsor mentioned that they would allow therapists who are in training. But again, thinking about, how should I put this delicately, for profit operations, which may misrepresent the training status of people who are unlicensed that they’re potentially in training when they’re actually not just to use the least resourced intensive personnel for their treatment, but it may, perhaps there needs to be, or can be more delineated guidelines as far as what that second therapist can be.
My personal feeling is that both should be licensed. But that’s for further discussions, but thank you.
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Elizabeth Joniak-Grant, PDAC [12:51:02]
I actually wanted to comment as well on the licensure. I think it’s for FDA and people to remember that oftentimes if you have one person who’s licensed and another person who is not a patient, will tend to see it as that person is sort of their advocate.
So if something is going wrong or awry, well, someone would speak up on my behalf. It’s, person A is doing something wrong. Person B would speak up on my behalf.
When you don’t have people of equal status in that relationship that can cause all kinds of problems when you get power imbalances and hierarchy. I’m thinking about what if you have, a senior professor and you have somebody who’s a graduate student who’s, you know, in the process, they’re going to call them out.
And there’s tons of instances of residents and fellows calling out bad behavior by clinicians all over the U.S., and nothing being done and nothing being investigated for years and years and years.
So I think we have to really think long and hard about that. I definitely hear what everyone is saying in terms of access, but we have to, you know, it is a balance.
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Dr Teresa Buracchio, FDA [12:57:26]
So we know that there is expectation bias and functional unblinding in this study. And it was something that we anticipated at the time of the review of these protocols. It was something that we actively discussed with the applicant during the special protocol assessment.
And so, we are not surprised by the results of the functional unblinding study. It is something that was anticipated. So we have to consider, when we think about how to handle this, we know that there is bias to these studies. We have to consider, factor that into our consideration of the results and how we tend to think about the bias about how to handle bias when we’re looking at the results is some of the things that were mentioned in the comments.
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Dr Teresa Buracchio, FDA [08:54:51]
I just wanted to make a general comment, not specific to this discussion, that I’ve heard some comments during our discussions about references to outside reports of potential misconduct in the studies.
And I just want to note that we, although we are aware of those reports, we consider them to be unverified at this point until we do our own inspections. So the discussions and voting should be based on what is contained within our briefing documents, as well as what you may have heard during the open public hearing, is also fair, but it should be limited to that data.
Due to privacy concerns, USDA does not have information about which affected herd is associated with the reported human case. However, USDA continues to sequence all confirmed positive samples, posting sequences on NCBI.
Anthony Fauci [00:57:18]
Another issue is that of Dr. David Morens, who has the title of senior advisor to the NIAID director, and who recently began, has been investigated for conduct unbecoming of a government official. Naturally, given his title, a connection is made to me.
With respect to his recent testimony before this subcommittee, I knew nothing of Dr Morens’ actions regarding Dr. Daszak, EcoHealth, or his emails.
It is important to point out for the record that despite his title, and even though he was helpful to me in writing scientific papers, Dr. Morens was not an advisor to me on institute policy or other substantive issues.
At NIAID we had weekly executive committee meetings of the institute leadership and daily morning meetings of my immediate staff. And to the best of my recollection, he attended neither of these.
Furthermore, his office is located in a different building from that of the NIAID director.
Finally, in a majority staff memorandum of May 22nd, 2024, there is a statement quote, Dr. Fauci may have conducted official business via personal email.
Let me state for the record that, to the best of my knowledge, I have never conducted official business using my personal email.
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Rep James Comer [01:14:12]
Dr. Morens testified that he could walk into your office anytime he wanted to. Is that true?
Anthony Fauci [01:14:17]
No, that’s not true. You don’t just walk into the office. I mean, he’s there, I mean, it’s conceivable–
Rep James Comer [01:14:22]
Did he ever walk into your office?
Anthony Fauci [01:14:24]
I would say he did occasionally, but the idea– can I finish the answer to you, sir?
Rep James Comer [01:14:29]
No, because I’ve got a lot of questions.
Anthony Fauci [01:14:30]
Okay.
Rep James Comer [01:14:31]
Dr. Fauci, did you ever delete an official record?
Anthony Fauci [01:14:34]
No.
Rep James Comer [01:14:35]
Dr. Fauci, did you ever conduct official business via email
Anthony Fauci [01:14:39]
To the best of my recollection and knowledge, I have never conducted official business via my private email.
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Rep James Comer [01:16:07]
On October 25th, 2021, Dr. Morens provided Dr. Daszak with advice regarding how to mislead NIH on EcoHealth’s late progress report. Does that violate policy?
Anthony Fauci [01:16:19]
That was wrong and inappropriate and violated policy.
Rep James Comer [01:16:23]
On December 7th, 2021, Dr. Morens wrote to the chair of EcoHealth’s board of directors to quote, put in a word for Dr. Daszak, does that violate policy?
Anthony Fauci [01:16:35]
He should not have done that, that was wrong.
Rep James Comer [01:16:38]
And that violates policy?
Anthony Fauci [01:16:39]
Well, I’m not sure of a specific policy, but I imagine it does violate policy. He should not have been doing that.
Rep James Comer [01:16:44]
In addition to all those actions, Dr. Morens wrote to Dr. Daszak quote, Peter from Tony’s numerous recent comments to me, they are trying to protect you, end quote. Did you ever talk to Dr. Morens about Dr. Daszak or EcoHealth Alliance?
Anthony Fauci [01:17:02]
I can tell you regard you what you said, I never spoke about protecting him. I mean, obviously we knew that Daszak was a grantee. So I may have mentioned and discussed Dr. Daszak because he’s a grantee, but I never spoke that–
Rep James Comer [01:17:17]
You’re testifying that he just made that up?
Anthony Fauci [01:17:19]
Excuse me?
Rep James Comer [01:17:20]
You’re testifying that, Dr Morens just made that up?
Anthony Fauci [01:17:24]
I don’t know where he got that, but that’s not true.
…
Rep Nicole Malliotakis [01:35:57]
Dr. Fauci, did you delete any emails or records related to the Wuhan lab or the origins of the virus?
Anthony Fauci [01:36:04]
No, I did not.
Rep Nicole Malliotakis [01:36:05]
Okay. Dr. Morens said in a May 2021 email, he indicated that he was connecting people to you in a quote secret back channel. Do you know what he was referring to?
Anthony Fauci [01:36:20]
I don’t have any idea what he’s talking about. There is no back channel at NIAID.
Rep Nicole Malliotakis [01:36:25]
Okay. There is, uh, he also sent another email that there is no worry about freedom of information act, I can send stuff to Tony on his private email. Did you communicate with anyone relating to anything regarding NIH or with Dr. Morens on a private email?
Anthony Fauci [01:36:44]
I do not do government business on my private email.
Rep Nicole Malliotakis [01:36:48]
Okay. So was there– so have you communicated with Dr. Morens via private email, even if it was not necessarily your definition of government business?
Anthony Fauci [01:36:57]
It might have been because as I mentioned in my opening statement, one of his functions is to write chapters, medical scientific chapters with me. So it is conceivable that I communicated with him on my private email when we were writing a chapter. And that was not official business.
CDC is aware of a flight from Vancouver, British Columbia, that arrived at Houston’s George Bush Intercontinental Airport on Friday, May 31. Public health officers from CDC’s Houston Port Health Station worked with EMS to evaluate ill passengers on board. Most of the ill passengers reported mild GI symptoms. No passengers were noted to have a fever during the flight or upon public health assessment at landing. No passengers met CDC criteria for further public health follow-up. Passengers from the flight continued with their travel plans.