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ASHISH JHA, WHITE HOUSE [00:08:08]
But one last point on this, Andy, because this administration obviously cares a lot about poor people who are uninsured, people who have been previously on Medicaid. We’ve been pushing hard to make sure that people can get enrolled in health insurance. And we have developing a plan. And I can be very confident about this. We are going to have a plan to make sure that uninsured Americans continue to get access to vaccines and treatments for free. Like that is a really important goal and we have set aside money to make sure that we can meet that goal.
ANDY SLAVITT [00:08:39]
Can you talk about that at all?
ASHISH JHA, WHITE HOUSE [00:08:42]
Yeah. Look, there are some parts of it I can talk about and some parts I can’t, only because we don’t know the details and we may not know for a while.
So, for instance, let’s talk about vaccines. The good news is if you have health insurance in America, you’re going to get vaccines for free. That’s not because of the largesse of any drug company or any insurance company. It’s because of the Affordable Care Act. The ACA makes sure that people who have who are insured, which is 92% of Americans, will get preventive services for free. But what about that other 8%? So we are working through there a couple of different mechanisms.
You know, obviously, it’ll depend on when there’s new vaccines. The current vaccines, we have plenty. So if an uninsured person walks into a CVS on on June 1st of this year, they’re going to get a free vaccine. At some point down the road, we may get an updated vaccine. And we are setting aside dollars to make sure that we have a plan to buy some for the uninsured. We’re working through what the distribution channels would be. Where can uninsured people get it? That is just being worked out. And obviously it’s hard to work out all those details now when that vaccine doesn’t even exist yet.
Similarly for treatments, we have plenty of treatments right now, and down the road we are going to make sure that there are treatment options available for the uninsured, that they can go get their Paxlovid if they’re eligible and not have to pay substantial money.
ANDY SLAVITT [00:10:03]
Well, that would certainly be great news.
ASHISH JHA, WHITE HOUSE [00:10:05]
I can tell you, Andy, this is not an aspiration. This is something we are going to get done.
…
ASHISH JHA, WHITE HOUSE [00:21:00]
Now, more specifically to your question around the White House, that second part of it, you may know this, I think you do, actually, I know you do, in the omnibus that was passed in December, Congress put in for the creation of a new office inside the White House, inside the EOP, the executive office of the president, called the Office of Pandemic Preparedness and Response, OPPR. They laid out a series of things that they thought the office should do. We think it’s a good idea to get this office together. And so obviously Congress legislated it. We are working on developing that office.
And there’s a lot of questions to be sorted out. Where exactly in the EOP does it sit? How is it going to get staffed? Who’s going to run it? All of those issues are being worked out right now, but that office will have a very important role in continuing to coordinate around COVID, coordinate around mpox, other diseases, other disease outbreaks that happen. And that is going to be an office dedicated to these issues inside the executive office of the president. And that’s going to be really, really important part of the federal government’s response.
ROCHELLE WALENSKY, CDC [00:10:17]
Well, let me just say, in that Health Affairs article, I was pretty pleased to see that CDC was on top of the other federal agencies.
So, I do want to say, like, I think that trust, we have work to do. And I don’t think it’s CDC alone. I think all of us have work to do. Science and academia has work to do and how we demonstrate and regain that trust because it has been so politicized.
One of the things that was the case when I came to CDC is our science was moving slowly. Has anybody ever tried to put a paper out with CDC co-authors? I hear people laughing. I was a co-author at the time. I started at CDC. And so I knew that.
And I said to the agency kind of the day I walked in the door, science gets out too slowly here. We have decreased our clearance time by 50% since the day I walked in the door. That’s still too slow as far as I’m concerned. And in fact, some of the things in terms of credibility is to be accountable and to say if you think your science gets out too fast, or too slowly, prove to me it’s going to get out faster.
So one of the things I think I’m really proud of is mpox vaccine performance. We were the first in the world to put it out. And we put it out via a technical brief on our website before it, when we were pretty sure as to what the data were showing, and when it was going through peer review, so we had every intent of putting it through peer review, but people needed to know how that vaccine was working.
We just last week, two weeks ago, put out a technical report on where we are with avian influenza. So so these technical reports, getting our science out faster. I fully believe in the peer review process and we still need to continue that peer review process because it makes it better. But often time to be action oriented in public health, we actually need to give information in real time before the ink is dry on the publication.
…
ROCHELLE WALENSKY, CDC [00:22:08]
So there’s just a lot of work in public health. It’s every week, I make unsung hero calls of people within the agency who may or may not have had their name in the news, or recognized for their work, but who are doing incredible work every day.
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ROCHELLE WALENSKY, CDC [00:27:04]
I think there’s this regulatory piece that is really EPA’s space. So we offer sort of the assessment of chemical exposure. But the regulatory piece is EPA space.
Interestingly, in East Palestine, there’s HHS, there’s EPA, and CDC, there’s HHS, and it bridged two regions, because Pennsylvania. And so there are a lot of players there in terms of both regulatory and health outcomes.
So CDC’s role, for the most part, is to assess the chemical exposure and to sort of do long term follow up. I think many people don’t recognize that oftentimes in many of these we have to be invited in order to be able to do that assessment.
So we have been on the ground in Ohio, and what we really like to do is especially provide community information that they need to do the assessment of chemical exposure to understand what those long term impacts are, and then also to understand and do the sort of science behind what is the potential impact of those exposures before and after they happen.
…
ROCHELLE WALENSKY, CDC [00:30:29]
Well, I was just saying ahead of this, it’s been raining infectious diseases since I got to CDC. And I don’t think that’s going to change.
Everybody thought that the next pandemic would be an influenza pandemic, and it wasn’t. And just because we had a COVID pandemic does not mean we are protected against an influenza pandemic. Our emergency operations center has been continually activated since I’ve started and had already been.
And so I think that we will continue to see infectious disease threats and we need to be ready for the next pandemic because we, I think, we had a frail public health infrastructure coming in and we’re doing a lot of work to bolster it, but it’s not where it needs to be.
All of that having been said, the people who are most impacted by infectious disease threats are those with chronic conditions. And it’s the intersection of those chronic conditions. And until we bridge that equity gap between the the people who are dying of chronic conditions and most threatened by infectious disease threats because of those chronic conditions, we will not be ready.
DAWN O’CONNELL, ASPR [00:15:34]
The previous administration, we needed that relationship with DOD very quickly, not only for those things that everybody knows about, the Operation Warp Speed effort when they came in and ran logistics and operations for that, but we also needed DOD to do our acquisitions. At HHS, we were not fast enough in our contracting and we had all of those contracts that needed to be executed immediately for the vaccines, for the therapeutics, and for the testing. And so what we ended up doing was entering into an MOU with DOD. And DOD has been doing assisted acquisitions for us since the very beginning of COVID. And our relationship with DOD in this space is going to end at the end of FY 23.
So one of the things I’m looking for is I’m thinking about PAHPA and in communication with Congress about what should go in that is what authorities does DOD have, did DOD have, that we did not? What made DOD capable of doing this so quickly and HHS couldn’t? And can I get those authorities for HHS?
It’s really important in this complex geopolitical landscape that we’re currently looking across that DOD be allowed to do DOD things and that HHS do HHS things. So we’ll be seeking some authorities that will help make our contracting and acquisitions efforts go a lot smoother and a lot quicker so we can stand up ourselves, should we hopefully not, but be faced with a similar outbreak that becomes a pandemic.
Likewise, we also saw very early in the response that FEMA came in and FEMA was able to surge staff in a way that HHS was not able to, and we needed their help to be able to meet the moment as it was happening to us. But what authorities does FEMA have, how can FEMA do their direct hire and their flexible pay in ways that HHS hasn’t been able to? Those are the other sets of questions I’m asking as I’m having conversations with Congress about what PAHPA should look like this time. Can HHS have those authorities? And in this world of complex disasters, can we let FEMA do what FEMA needs to do and let HHS do what HHS needs to do?
So those are the things I’m thinking about, is how we take the transformation that’s happened in these last three years that’s had to happen and make sure that it’s consistent with the authorities we have in PAHPA for now and moving forward.
…
DAWN O’CONNELL, ASPR [00:37:55]
We’re seeing a lot of changes because of climate change. We’re seeing a lot of more common disasters happen more frequently. I was at a FEMA conference recently where they were talking about the poly disaster, where there’s just disaster after disaster, whether it’s the fires, the winds, the storms and ASPR we do, in addition to our work on pandemics and other countermeasures through BARDA, and our distribution networks, we also have the NDMS teams. These are teams of clinicians that get deployed to help in a disaster or help a community respond to a disaster. And making sure that they are strengthened, I think is going to be really important for PAHPA making sure that we continue to have this resource.
They were exhausted after three years of COVID plus plus hurricanes, plus plus wildfires, plus plus all the things that they’ve had to respond to. So making sure that they have the strength and support in this next one, I think, is going to help in the all hazards.
The other thing I’ll say about BARDA that’s been, I think, right ,in addition to what Tom was describing with Disease X, which is we don’t know what’s coming next, is they’re looking at threat agnostic countermeasures. You know, we were one bug, one drug. We are now looking at taking care of whatever the symptoms are, whatever the after effects are, no matter what the cause is, and making sure that we have countermeasures available to treat the people that are injured, whatever that– whatever caused the injury, make sure that we can get to to the source of their pain and provide some protection.
So we’re going to continue to look for ways to do that and strengthen that.
TEDROS ADHANOM GHEBREYESUS, WHO [00:03:42]
In Tanzania, the number of confirmed cases remains at eight with five deaths. Three people are currently being treated in a health facility. Two health workers are among the confirmed cases, including one death. So far, all of the reported cases are in one region.
WHO and partners, including UNICEF, the U.S. CDC, and MSF have offered support to the government to bridge any gaps in the response.
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MIKE RYAN, WHO [00:15:32]
And just to confirm that our country representatives in both Equatorial Guinea and Tanzania have been engaging with the ministry of health and have offered this assistance in terms of setting up these trials. And again, under the leadership, as was the case in Uganda, of the ministry of health and principal investigators from scientific institutions within those two countries.
Obviously, we would like, in the longer term, to be in a position to set up a stockpile like we have for Ebola Zaire vaccine, which is maintained by ourselves, with our colleagues in GAVI and our colleagues within UNICEF, and others, who maintain a global stockpile of registered vaccine now that is available free of charge to countries on the basis of need. So we have a global capacity to support those countries affected by Ebola Zaire.
We don’t have that solution yet for Ebola Sudan, nor for the Marburg virus. These kinds of investigations and trials would offer us the opportunity to advance our knowledge and the clinical evidence around the use of these products would accelerate us towards registration of these products and then the possibility of being able to stockpile those products on behalf of all of the countries, and in this case, the countries most at risk from both Sudan virus disease and from Marburg virus, are African countries.
So we would hope through the process, working with AVAREF and others, working with other partners on the continent, and working with the international partners. And I have to say that the international partners who have worked with us on this, both in terms of our colleagues at GAVI, our colleagues at CEPI, our colleagues at UNICEF, and our colleagues in BARDA, our colleagues in many other– Ana Maria will probably come back with a list of all those, because I actually think we are making progress. We’re making progress in aligning international support, international innovation, but to support regional innovation, regional application, national intervention.
And I think, if we can– the products are ready, the process is ready. We now need to get those vaccines on the ground and be able to gather the clinical evidence that will allow us to progress these vital products further towards registration and stockpiling.
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ABDI MAHAMUD, WHO [00:21:29]
When we have an outbreak there, we encourage countries to increase the sensitivity of the surveillance. And thanks to the Burundi government for reacting to that and establishing a very sensitive surveillance.
In Burundi, we are aware of nine alerts and three of them have been already dead and the samples were taken. Initial samples taken when they were alive showed negative for Marburg, for Ebola, and dengue. But the team is working closely with our regional office, sending that sample to the neighboring country of Uganda, and to the WHO regional office, regional collaborating centers for further confirmation. But all the countries at this stage, since it’s the subregional, we encouraged to have a very sensitive surveillance to pick all alerts and more alerts to be picked up. So at this stage, later investigation is going on, and will share when we have more.
Once again, thanking Burundi authority and all the countries in the region for establishing a very sensitive surveillance that’s able to pick up cases. As of now, the initial tests are negative, but we know very well there’s a long differential diagnosis. And until we have confirmation from the UVRI lab in Uganda and the WHO collaborating centers, all the diagnoses are still in play. So establishing contact tracing, community engagement, all the pillars of the response needs to be strengthened, all the countries neighboring Tanzania.
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ANA MARIA RESTREPO, WHO [00:30:41]
So what I am telling you is that we don’t need thousands of doses because this is not a population level vaccination. But our experience suggest that vaccinating around the contacts of each case that is a handful of people at higher risk, it is possible to document whether or not the vaccines are effective and to contribute to stop transmission with the other measures.
Now to the numbers. As we mentioned last time, the Sabin ChAd3 vaccine Marburg has 750 doses available. 750 doses and 8,000 in bulk. Going back to my example, this is like having doses for about 200 rings, 200 cases of Marburg. Keep that in mind.
Now let’s talk about IAVI and the VSV vaccine they have. They have several hundred doses frozen GMP material that they are putting into vials. So they are not ready yet, but they will be available.
Let’s go to Auro and Emergent. They have lots of, thousands of doses available, in late 2023. And the University of Oxford, they have doses, 1,000 doses. So it’s equal to about another 200 cases with the rings around. If we go to the Public Health vaccines, another VSV vaccine, they also have several hundred doses ready to be used.
So when Dr. Tedros tells you that we have the doses of vaccines ready, is not that because we are saying there are millions of doses out there. But, because based on our experience, we have sufficient doses to make rings of cases around all the contacts of these cases of Marburg. Finally, my last statement is, typically, the Marburg outbreaks are small. The largest was about 300 cases. So that concludes our assessment of that.
And remember that in the background of these numbers, there are all these developers working to put the bulk vaccines into vials and to increase their capacity.
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ABDI MAHAMUD, WHO [00:33:38]
As I explained in the previous press conference, in Equatorial system– Equatorial Guinea has two way of committees. We have the technical committee where WHO is active member with our teams, as director general mentioned, in the field providing clinical management, together with CDC, supporting the lab. So sometimes we get advanced information that have to be reviewed by the political committee, and then reported to WHO through IHR.
But the worrisome part is what DG said. These are to sight of the widespread of the transmission that making us worrisome. And we have been offering, through director general’s letters, offer to the government, because this outbreak, as it stands, is larger and we may be seeing in more provinces and that more than the case count, the number, is the extent and the geographical spread.
So we’ve been requesting the government of Equatorial Guinea and there have been opening, giving experts, 20 experts from WHO visa on arrival. So expediting that will really help the country as they don’t have experience in dealing with that.
So answer your questions. So those those cases are lab confirmed, but is going through the– from technical committee to the political committee, and then it’s reported to the WHO. Every country has a unique way of clearance process, but we get sometimes advanced information, as our team are out there providing clinical care, case management in the field.
So we, hopefully, within the next day, today or tomorrow, will be able to get their final certified information through the IHR.
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MIKE RYAN, WHO [00:35:30]
There’s always a slight delay between the case when confirmed on the ground and having an official report. That’s not my concern.
The concern I have is that all governments, when we’re in the middle of an outbreak, and we have new and significant information, particularly related to lab confirmed cases of dangerous pathogens, is that communities need to be made aware, communities need to be put on the alert, and communities need to be able to take action. Any delay in releasing information related to lab confirmed cases, especially when it relates to newly affected areas, prevents the process of alerting communities, and having them take action to protect themselves and their families.
So this is not just a legal requirement in some international law. This is a sovereign and solemn requirement of all states to inform their own people of what is going on in their country, to the best of their knowledge. And yes, there have to be checks done, and yes, results have to be validated. And it’s a very important process that governments have time to be able to do that.
But what we can’t have is unnecessary delays in reporting disease to one’s own people. The international requirements are clear, but the primary responsibility is to one’s own people.
HANNA NOHYNEK, SAGE [00:18:04]
Actually, if we look at the big picture, we say 12 months in the high priority use group, but then there is a subgroup of, like you mentioned, older adults or older adults with multiple significant comorbidities. And for those people, one could go down as low as six months. So there is a subpopulation.
But the kind of overall recommendation is that the most efficient use of the COVID vaccines in these older adults and young adults with significant comorbidities or severe obesity would be the 12 months.
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KATE O’BRIEN, WHO [00:22:42]
We’ve used this term not routinely recommended, and I think it would be relevant and important to describe what it is we mean by that. When the text comes out, you will see the text. But what is intended by the term from SAGE of not routinely recommended? It means that a vaccine in that category is not recommended for inclusion in the routine program that would be recommended for all people within that category because of minimal public health impact and low cost effectiveness in most settings.
But the vaccine could be offered, as, as Dr. Nohynek said, in individual circumstances, where there would be an added benefit to be expected for a particular circumstance, recognizing that there are no known additional safety issues associated with giving additional booster doses.
And we do acknowledge that some countries may elect to offer such doses in the routine program based on their own specific population risk or the disease epidemiology or other programmatic priorities.
Of course, SAGE is in the business of having to provide global recommendations, and we’re really at a point in the pandemic now where the sort of country context and the country programmatic prioritization is starting to play a bigger and bigger role.
And so what SAGE is trying to do is to provide a broad global guidance around what the evidence is. And we do recognize that there may be specific countries where the specific context of the country may deviate from the overarching recommendations, so that that notation for country specificity is important.
…
HELEN BRANSWELL, STAT [00:27:30]
Did the SAGE discuss the process for updating vaccines? Or is that solely the responsibility of the committee that Kanta Subbarao chairs, I think, that’s the committee?
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KATE O’BRIEN, WHO [00:28:07]
Helen. Yes, you’re correct. Within WHO, we have expert committees that advise the director general on different elements of the health emergencies. For COVID, we have the emergency committee, which is the committee that is advising around IHR issues. And that committee is the committee that also is advising around the determination of public health emergency of international concern.
The second committee is the technical advisory group on the composition of vaccines, the TAG CO VAC. That’s the one that you referenced, that Dr. Kanta Subbarao is the external expert chair. That committee has also met recently and will be releasing a statement soon.
So the third committee is the SAGE, which is around the policies of the vaccines that are authorized for use. And SAGE has already made statements about the variant containing vaccines. And the use of those vaccines, either in primary series, parts of the schedule, or as booster doses. The evidence has been reviewed around the performance of the bivalent vaccines relative to the, let’s call them, the ancestral strain vaccines, the monovalent vaccines. And this is the same evidence that has been reviewed by TAG CO VAC as well.
And at SAGE, at this particular meeting that we just held, again, we reviewed the evidence. And that evidence does show that, first of all, I would note, that it’s very difficult to find studies that compare the use of monovalent vaccine with the use of bivalent vaccine for the same dose. What is often in the literature is evidence around using the bivalent vaccine and just what its absolute benefit is for a particular dose, but not in comparison to whether or not the same benefit would have been accrued if that dose had been given with the monovalent vaccine. So it’s important, as anybody is looking at the evidence, if the question is, does the bivalent vaccine work? That’s one question. And yes, it it works. If the question is, does it work better than the monovalent vaccine, given that about 70% of the world’s population is using vaccines that are not the mRNA vaccines, and it’s only the mRNA vaccines that have these bivalent products.
So when the question is asked, is a bivalent product better than getting a monovalent product? What we see is that, first of all, there’s very minimal evidence on this question. Secondly, there is some additional benefit for symptomatic disease by giving the bivalent compared with the monovalent. But for severe disease, we have no evidence that that the bivalent product is better than the monovalent product. So that’s just a quick summary of where the evidence from clinical use of the vaccines comes from.
And it is the TAG CO VAC that advises in an ongoing way about the composition of the vaccines.
As you know, GISAID regularly assists data contributors with their efforts to improve their data. This includes researchers from the China CDC who recently completed their updates. Therefore, these data are once again visible to all users.
Nothing revised. It is GISAID internal issue.
The chart presented in the video is from a presentation that was shared during a meeting between CDC and WHO in January of this year. Poliovirus wastewater surveillance is ongoing in New York State and New York City. For the most up to date data, please see the New York State reports, which are updated regularly and linked to from this page: Polio Wastewater Surveillance (ny.gov). There are no additional data for the other jurisdictions that appear in the chart.
Other than the single paralytic polio case identified in NY last summer, there are no known cases of paralytic polio in the United States or Canada right now. The risk to the public is low because most people are vaccinated against poliovirus during childhood. Access to clean water, good hand hygiene habits and modern sewage systems also help prevent viruses like poliovirus from spreading.
Widespread wastewater testing for poliovirus is not routinely recommended at this time. The best way to protect everyone from polio is to maintain high immunity against poliovirus in the population through vaccination.
At this time, there are no additional confirmed cases of measles connected with the exposure at Asbury University.
STEPHANE BANCEL, MODERNA [10:53:06]
I care deeply about access and protecting people. That’s why we say the company is to help protect people. We will advertise it and communicate about it as we get into the fall. As you know, as of today, the government is still in charge of vaccine distribution. So we don’t want to confuse things for the U.S. consumer.
But as we get closer to the fall, we’ll make sure we get the word out. As I mentioned, we want to work with rural hospitals, community hospital, homeless shelters, because I really believe there is a better way to give access to people that are uninsured. We have heard loud and clear that the system set up by big companies is too complicated, too much paperwork, takes too much time.
SEN SHELLEY MOORE CAPITO [01:55:14]
The last question I have is the budget includes a proposal for 20 billion dollars in new mandatory funding for pandemic preparedness and response. So I want to be clear here. I am supportive of efforts to bolster our nation’s pandemic preparedness and response, but I am concerned that this is sending mixed messages, because HHS came to us last year for 82 billion dollars, so now it’s down to 20 billion dollars.
What’s the difference in this request? Because it wasn’t granted, because it was– just for a lot of reasons. I’ll leave it like that.
XAVIER BECERRA, HHS [01:55:55]
Honest truth. We could use the 80 billion. We don’t expect that you all will give us the 80 billion. We hope that you would at least give us the 20 to 30 billion, because in order to prepare, let’s put it this way, to prepare, it takes a lot of work. We saw how much we had to spend once we were in the pandemic. We could absolutely use that money to prepare, to get states better prepared.
But we want to be realistic. What will you move with? We think that 20 to 30 billion dollars is a good place to go. That gets us at least in a place where we’re preparing.
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XAVIER BECERRA, HHS [02:00:39]
I would love to have Administrator Dawn O’Connell speak to you and your staff directly or to any members of the staff, because we have depleted the stockpile. And we we need to get back to, for example, when we did mpox monkeypox, we used a lot of the smallpox vaccines that we are storing in the event smallpox should ever hit this country, because that vaccine also worked against the monkeypox, against mpox, we started using some of that vaccine.
We need to replenish that. We’ve got no money to address mpox. And so we took that out of the stockpile. To replenish those smallpox vaccines will cost money. But we need to. And so I absolutely want you to have sight, because neither you nor I wants to be caught flat footed if we find that our stockpile is depleted. So we will follow up.
WILLIAM SCHAFFNER, NFID [00:18:35]
You tell me about a vaccine, another bivalent vaccine that may be available this fall. But what about right now? Should I get a second bivalent booster to, in effect, carry me through the summer? Are there such recommendations?
JESSICA MACNEIL, CDC [00:18:58]
This is another thing that the workgroup is looking at, particularly for certain groups that are at higher risk of severe outcomes from COVID. And so, thinking about the older adults and immunocompromised individuals. And so I don’t think that there’s anything immediately on the horizon, but it’s certainly something the work group is looking at the data and thinking very carefully about.
I think for COVID vaccines, we have the added challenge of things have to be approved by FDA before ACIP can consider it. So I think that there is– I think it’s definitely on people’s radars and people are thinking about it, but it’s not imminent, as far as I know.
QUESTION [00:03:15]
Will we be getting a new booster? You know, it’s been six months since most of us got the bivalent that might cover every kind of variant, but we’re not seeing it right now. And infectious disease expert Peter Hotez recently tweeted he would keep his opinion on whether there should be another booster to himself, in order not to undermine the CDC. And that kind of implied that he thought another one was needed. Put all that aside, what’s your thoughts? Should we have another booster?
ASHISH JHA, WHITE HOUSE [00:03:41]
So from the beginning of this pandemic, you know, one of the things I’ve said before I came to the administration, we’ve got to be guided by evidence and data. So on the question of whether there should be a second booster, let’s say, for high risk individuals, right now, the FDA scientists are looking at the evidence that’s out there, looking at the data.
They have not made a determination. And when they do, of course, we’ll all know about it and we’ll share that widely. But FDA is looking at this actively and is going to make a decision based on what their assessment of the data is.
We continue to closely monitor the emerging data in the United States and globally, and we will base any decision on additional updated boosters upon those data. Importantly, individuals who have not yet received an updated (bivalent) booster are encouraged to speak with their health care provider and consider receiving one.
As discussed during the January VRBPAC, we hope that simplifying the COVID-19 vaccine regimen in the not too distant future will lead to the vaccination of more individuals in the coming years as we learn to live alongside SARS-CoV-2 – potentially reducing serious outcomes, including hospitalization and death.
We are focused on our supplemental biologics licensing application. However, ultimately the cadence will be determined by FDA and ACIP for recommended timing.
We submitted our sBLA, it is only under EUA right now, so the sBLA will be to request for a formal approval. Based on if and when the FDA makes that decision, the ACIP will provide recommendations on timing.
The 3 deaths are deaths within 30 days of the VIM-P aeruginosa specimen collection. Two patients had confirmed use of EzriCare and one patient is not known to have used EzriCare, but is epidemiologically linked to patients who did. Pseudomonas was a contributing case of death for one patient; for other two patients the role of Pseudomonas in the death is unknown.
UNOS supports initiatives to strengthen the system
UNOS supports HRSA’s plan to introduce additional reforms into the nation’s organ donation and transplantation system. We also stand united with HRSA in our shared goal to get as many donor organs as possible to the patients in need while increasing accountability, transparency and oversight.
We welcome a competitive and open bidding process for the next OPTN contract to advance our efforts to save as many lives as possible, as equitably as possible. We believe we have the experience and expertise required to best serve the nation’s patients and to help implement HRSA’s proposed initiatives. Numerous components of HRSA’s plan also align with our new action agenda, which is a list of specific proposals we outlined earlier this year aimed at driving improvement across the system.
We are committed to working with HRSA, HHS, Congress and others who care about this system so deeply to assist in carrying out these reforms and to do our part to improve how we serve America’s organ donors, transplant patients and their families.
We’ve not treated any patients up until now. We have received three bacterial isolates from the CDC repository that are associated with this outbreak and our laboratory group has identified at least one phage with activity against the isolates. We and other collaborators are continuing to screen for additional active phages.
The approach we take is that we respond to inquiries from physicians about patients they feel might benefit from phage therapy and, if it appears that phages might be beneficial in a particular patient, we work with the physician to see if we can identify active phage(s) and we then help them with some of the intricacies of obtaining and using them. Up until this point we have not had any patient or physician inquiries.
NATALIE THORNBURG, CDC [00:09:50]
So XBB.1.5, which is a BA.2 lineage virus, has been the predominant circulating viruses nationally for quite a while now. It is sitting at about 90% of circulating viruses nationally. It has been diversifying over the past month, month and a half, because it’s just the predominant virus. And we recently broke out a sublineage from XBB.1.5 and that one is shown right here, XBB.1.5.1. That virus has one additional change in its spike protein in comparison to its parent lineage. And that change is– sorry, let me take a quick look, remind myself– is in the position 573 in the spike protein.
There has been some viruses circulating more dominantly internationally. XBB.1.9, that is not currently broken out on the data tracker. It is aggregated. It is in the data tracker, but it is aggregated with its parent lineage, XBB. That virus that is predominant in some other parts of the world is XBB.1.9, so that is on the data tracker aggregated with XBB. That virus has the same spike sequence as XBB.1.5. So it has the same spike sequence but evolved independently, meaning it is convergent evolution. So it is in that XBB, and so nationally it as well as other XBB lineage viruses, represent about two to two and a half percent of circulating viruses nationally.
Regionally, XBB.1.5 is still the predominant circulating virus in all regions, and that’s this dark blue color. Some regions are showing predominantly or showing higher percentages of some other lineages though for the first time in several weeks, like region seven, for example, is showing a bigger prevalence of XBB viruses than region one and region two, although still a minority of circulating viruses.
…
TIM STENZEL, FDA [00:15:03]
In talking about what would happen, what would bring the 564 to an end? And there is planning for it. And there is a draft guidance out there that describes the transition period between the end of a 564 declaration and what would happen before tests would might have to be taken off the market. And in particular, commercial kits that are currently on the market.
So the FDA would like to see that that many more test kits are converted to full authorization. And then this would allow to testing on the market, after the end of the 564. The reason why 564 authorities are likely needed beyond the end of the PHE is that we haven’t had enough submissions and enough authorizations, full authorizations, clearances basically, of tests so that we can supply– so that the nation has a supply of authorized tests that can continue to be to used for COVID.
So we are encouraging submissions and we are reviewing the ones we have and we have been making such authorizations. The most recent was a grant for a point of care antigen test, and that was the first antigen test that was fully converted. And so we just need to see more, so that we know there’s assurance of long term availability of authorized test kits for COVID.
…
TIM STENZEL, FDA [00:17:10]
The mpox public health emergency ended on January 31st of this year, and the 564 declaration for mpox remains. And that’s very important because very few of the authorizations were even authorized on prospectively collected mpox samples. And to be able to do a prospective study now, to collect some of those needed mpox samples with mpox numbers being so low, which is good, would be obviously nigh on impossible.
So it’s quite likely that the 564 mpox declaration will remain in effect for probably a very long time.
…
TIM STENZEL, FDA [00:38:31]
So this is the conversion from an EUA authorized test to a full authorized test. When that happens, we remove the 564 authorization for that test, and we ask the manufacturer to notify their customer base. So if you’re a customer of an EUA test and it gets fully authorized, the manufacturer of that test should notify you.
And there will be a conversion period where you can continue to use the EUA kits before hopefully until they– you use them all or the expiration date is hit, then you can convert to the fully authorized test so that there’s not a– so that it’s an efficient process. You don’t have to spend extra money and waste, the kits that you might have.
So the FDA takes a look at this. We care about that. We care about making life as easy as possible for labs that are using EUA test kits now and want to have access to tests.
Thank you for reaching out to us. For nearly 15 years, the GISAID data science initiative has been an essential contributor to global health security by enabling the rapid sharing of genomic and associated metadata during major public health emergency situations, thus facilitating public health responses and the development of lifesaving countermeasures.
To continuously improve the quality of data records, data contributors frequently update their records, e.g., when higher-resolution sequences or additional metadata become available, or when verification is required. With the help of GISAID’s data curation team, released records may from time to time become temporarily invisible to allow for such improvements. Some scenarios may arise where, for example, a duplicate sequence or erroneous data (due to a contaminated sample) are recalled and thus are no longer visible in a GISAID database. GISAID does not delete records.
This scenario also applies to records submitted by the China CDC that are currently being updated with newer and additional data as part of a manuscript currently under review.
TEDROS ADHANOM GHEBREYESUS, WHO [00:05:25]
Last Sunday, WHO was made aware of data published on the GISAID database in late January and taken down again recently.
The data from the Chinese Center for Disease Control and Prevention relates to samples taken at the Huanan market in Wuhan in 2020. While it was online, scientists from a number of countries downloaded the data and analyzed it. As soon as we became aware of this data, we contacted the Chinese CDC and urged them to share it with WHO and the international scientific community so it can be analyzed. We also convened the Scientific Advisory Group for the Origins of Novel Pathogens, or SAGO, which met on Tuesday.
We asked researchers from the Chinese CDC and the international group of scientists to present their analysis of the data to SAGO.
This data do not provide a definitive answer to the question of how the pandemic began. But every piece of data is important in moving us closer to that answer. And every piece of data relating to studying the origins of COVID 19 needs to be shared with the international community immediately.
This data could have and should have been shared three years ago. We continue to call on China to be transparent in sharing data and to conduct the necessary investigations and share the results. Understanding how the pandemic began remains both a moral and scientific imperative.
…
MARIA VAN KERKHOVE, WHO [00:12:59]
The information that we have been made aware of, we were presented results by China CDC, as well as by researchers from around the world who downloaded this data. And what they were looking at is some molecular evidence of samples that were collected from the Huanan market in January 2020.
And what they found, what they presented to us, is that they found molecular evidence that animals were sold at that market, and that was suspected, but they found molecular evidence of that, and also that some of the animals that were there were susceptible to SARS-CoV-2 infection. And some of these animals include raccoon dogs.
Unfortunately, this doesn’t give us the answer of how the pandemic began, but it does provide more clues. And we once again reiterate that there are many more studies that need to be carried out. These studies have been recommended over many years, looking at the source of the animals of the market, looking at potential intermediate hosts, looking at breaches in biosafety, biosecurity. These studies have yet to be conducted.
And until they are conducted, until we have the data, we aren’t able to conclusively say how this pandemic began. So the work continues. And that’s the point here. Any data that exists on the study of the origins of this pandemic need to be made available immediately.
…
MARIA VAN KERKHOVE, WHO [00:16:41]
The challenge that we have is that there is data that is out there that exists that has not been made available to us, that has not been made available to the SAGO, and has not been made available to the international community. So we need to look at the full picture, and that’s what we’re calling on.
And until we have that information, we won’t be able to remove different hypotheses. So that’s what we mean when we say that all hypotheses remain on the table. We need to pursue each one of these until they can be removed. And at the present time, we’re not able to take any of those off the table.
…
MARIA VAN KERKHOVE, WHO [00:18:37]
What we understand is that this data was submitted by China CDC as part of their work in and writing a publication, a publication that was submitted last year and put up as a preprint. That preprint is available. And our understanding is that research, that paper, has been updated and resubmitted.
And in the resubmission, China CDC put more data available on GISAID. Don’t know the situation, the circumstances in which the data was released and taken down. We have been told by GISAID that the data from China CDC is being updated and expanded. But again, we have called on China CDC directly to make that data accessible in full. And so that remains absolutely fundamental.
…
MARIA VAN KERKHOVE, WHO [00:20:50]
This more detailed analysis really takes a deeper dive into the available information and the metadata that is associated with these sequences and doing some metagenomics work. It’s very detailed work of looking at DNA within those samples as well.
What the updated results that were presented to us suggest, and again, these were results that have been presented to us by international researchers who downloaded that data, was number one, is that there’s molecular evidence that animals were sold at the Huanan market, and that is that is new information. And secondly, that those animals that the DNA that was identified include a number of different animals, including these raccoon dogs.
And from other studies, we know that raccoon dogs are susceptible to SARS-CoV-2 infection. So we need to make clear that the virus has not been identified in an animal in the market or in animal samples from the market, nor have we actually found the animals that infected humans. What this does is provides clues. It provides clues to help us understand what may have happened.
One of the big pieces of information that we do not have at the present time are the source of where these animals came from. Were these animals traded? Were they the wild animals or domestic animals? Were they farmed? Where were they farmed?
We have repeatedly asked for studies to be done in other markets in Wuhan and in Hubei and across China. We have repeatedly asked for studies to trace those animals back to their source farms so that we can go back in time and actually look to see where the animals came from and if any testing had been done. We repeatedly asked for serology to be conducted of people who worked in the markets, perhaps people who worked on farms where these animals came from.
So there’s a lot of unanswered questions. So this updated information provides an additional clue in terms of looking at a potential intermediate host of how some people became infected.
JOHN FARLEY, FDA [00:20:04]
As you’re aware, FDA authorized the emergency use of Paxlovid on December 22, 2021. Note that the authorization is the treatment of certain adults and pediatric patients 12 years of age and older and weighing at least 40 kilograms.
Our discussion today will not focus on pediatric use, as pediatric drug development is ongoing. Should this new drug application be approved, FDA anticipates that the EUA for Paxlovid will remain in effect to continue authorizing treatment of adolescents with mild to moderate COVID-19 and further address other access needs.
…
PATRICK HARRINGTON, FDA [02:08:34]
I’m just going to start by stating that FDA is in alignment with the applicant on the impact of Paxlovid on COVID 19 rebound.
Specifically, analyses of virologic and symptom reporting data from the EPIC HR and EPIC SR trials showed a subset of Paxlovid and placebo treated subjects experienced virologic and or symptomatic rebound after the end of treatment on day five. And there was no clear or consistent association between virologic or symptomatic rebound and Paxlovid use.
…
PATRICK HARRINGTON, FDA [02:23:47]
Based on these analyses of virology and clinical outcome data from the double blind, placebo controlled, EPIC HR and EPIC SR trials, we have concluded that rebound in SARS-CoV-2 RNA or virus shedding or COVID 19 symptoms, occurs in a subset of infections, is not clearly associated with Paxlovid treatment, is not associated with severe disease outcomes, and likely reflects natural COVID 19 disease progression and or technical variability in virology assessments.
…
STEPHANIE TROY, FDA [02:26:27]
We’ve also approved a number of emergency INDs for prolonged use of Paxlovid from 10 to 28 days in severely immunosuppressed patients with persistent SARS-CoV-2 infection that range from about one month to up to six months of persistent SARS-CoV-2 positivity in nasopharyngeal swabs or in samples. We now have outcome data from 15 of these patients.
Two of the patients died, but one was in the intensive care unit at baseline and died on day two of Paxlovid treatment, and the other had a number of other complications like cavitary pulmonary aspergillosis and had decreasing SARS-CoV-2 RNA levels at the time of death.
The other 13 reported improvement, either in terms of symptoms or viral clearance or in many cases, both, with some patients reporting full recovery.
While these results are encouraging the small numbers, along with the heterogeneity of dosing durations, the use of other antivirals, the varied clinical presentations and the lack of a control group limit the interpretation of these results.
…
JAMES RUSNAK, PFIZER [03:54:43]
So our overall design for the EPIC peds 1026 trial is shown here. It is a five cohort study starting with the oldest age children, and then we will successfully work down through the cohorts sequentially until we get into a very young neonatal population.
We have most of the cohort one previously enrolled. We did some evaluation of this and decided to increase the overall sample size of this cohort. So that will begin to enroll again. And I do believe that we’ll have that data from that cohort prior to the end of the year.
For the other study, the cohort for pregnant women, the special population, if I could have slide BU 237? So this shows the– if we could show that slide, please.
So this shows the design of the EPIC pregnancy study, study 1035. Overall, 45 patients will be enrolled. There is a stratification into cohort one and two. Depending upon the trimester, we will intend to enroll 15 from each of those as well as a non pregnant cohort.
The non-pregnant cohort was recruited very quickly and it has been full for some time. And in the other cohorts one and two, we have two subjects today. It’s been rather challenging to enroll this study.
…
JAMES RUSNAK, PFIZER [04:34:59]
So five days was selected in part based upon other antiviral therapies used for upper respiratory infection as well as a quantitative systems pharmacology model. You know, with the dose that we selected and with the treatment duration that we selected, we had, as you saw, a very robust relative risk reduction as well as an absolute risk reduction in EPIC HR.
For most patients, more than 80% of the patients, they have no incidence of symptomatic rebound or viral load rebound. For those that do experience symptomatic rebound, they’re generally you know mild, self-limited and do not result in severe outcomes.
…
JAMES RUSNAK, PFIZER [04:35:44]
For the patients that do have symptomatic rebound, we have an ongoing trial looking at retreatment. So patients would have to have a documented treatment course of Paxlovid and then followed up by resolution of symptoms, rebound of symptoms, and then a positive rapid antigen test within the first 14 days following cessation of the first five day course.
That trial is ongoing. It will be reported out in the third quarter of this year, and it’s about two thirds of the way recruited.
…
JAMES RUSNAK, PFIZER [04:36:15]
For the highest unmet medical need, that really comes back to the immunocompromised patient population. And for that, we have the ongoing study. And I think that we can continue to understand what’s the optimal treatment duration for that particular population. But we have a high degree of confidence that five days is right for the general population.
…
STEPHANIE TROY, FDA [04:36:41]
I would agree that we do have a high degree of confidence that for the general, high risk population, five days is is the optimal duration. And we do have the data that five days of treatment from the clinical trials showed a significant benefit in terms of reduction of hospitalization and death.
I also agree that the biggest group with the unmet need, the highly immunocompromised patients, that we still don’t know if a longer treatment duration would be better and that hopefully we’ll be getting that data this year.
…
JAMES RUSNAK, PFIZER
[04:36:15]
For the highest unmet medical need, that really comes back to the immunocompromised patient population. And for that, we have the ongoing study. And I think that we can continue to understand what’s the optimal treatment duration for that particular population. But we have a high degree of confidence that five days is right for the general population.
…
STEPHANIE TROY, FDA [04:36:41]
I would agree that we do have a high degree of confidence that for the general, high risk population, five days is is the optimal duration. And we do have the data that five days of treatment from the clinical trials showed a significant benefit in terms of reduction of hospitalization and death.
I also agree that the biggest group with the unmet need, the highly immunocompromised patients, that we still don’t know if a longer treatment duration would be better and that hopefully we’ll be getting that data this year.
…
STEPHANIE TROY, FDA [04:49:33]
Labeling discussions are broadly are something we’re going to be that are ongoing, so we can’t discuss labeling recommendations too much at this point. But I can say that, at least in instructions for how to take it, there would be something in there about taking it within five days. Most likely.
…
LINDSEY BADEN, AMDAC (Chair) [05:40:41]
The overwhelming sense of the committee is that efficacy and safety have been demonstrated. It is important to understand who’s at high risk, which we will discuss shortly to understand who’s likely to benefit.
The issue of viral resistance emerging seems to be a low, at least given the available data which does not show such a concern, as different variants have emerged, which is reassuring.
The lack of alternative therapies that are easy to give oral, outpatient and effective also increases the importance. The heavy use in the community is reassuring over the last year in terms of safety. The drug drug interactions is a significant concern and that has been discussed and requires continued attention.
And the issue of both those who said yes and our colleague who said no is how do we support patients and providers to understand where this fits in? And our colleague who voted no expresses a concern that the community doesn’t understand where this fits in, who will benefit, and therefore being able to access and use this in an appropriate and timely manner.
…
RICHARD MURPHY, AMDAC (Member) [06:07:06]
I just wanted to say that I think the understanding of which risk factors are meaningful today in the context of vaccination to inform the use of Paxlovid is probably not going to come from clinical trials.
I’m thinking that it’s going to come from large health systems that can isolate specific risk factors and match them with patients who have the same risk factors and don’t benefit from Paxlovid or don’t receive Paxlovid. So I think more research needs to be done, but I don’t think it’s going to be clinical trials on this issue.
LINDSEY BADEN, AMDAC (Chair) [06:07:51]
The point is well taken. And what I was getting at in a clumsy way is I’m not convinced a BMI of 25.1 has the same weight in terms of risk as age of 90. But that’s an impression. And how to generate the data to inform that Dr. Murphy may well need to come from large health system data sets, albeit complicated by individual choice in terms of who’s health seeking and who isn’t, and how that that bias can be mitigated.
…
SANKAR SWAMINATHAN, AMDAC (Member) [06:10:39]
I think there’s a broad lack of of understanding not only among the physicians but among patients. And it concerns me that not only are there patients, as she described, who are not offered the drug, who would clearly be candidates for it, but I’ve had many patients who I’ve seen for other reasons who have told me that they had COVID.
And I’ve always asked them, were you treated and how did that go? And there have been a distressingly large number of patients who told me, ‘Oh, I was told that I shouldn’t take it because of rebound.’ And these are patients who, you know, some of them had cancer, some of them clearly should have been offered it. And knowing their their medical history, they really had no contraindication to its use.
And I’m concerned that there’s not a good understanding among the medical community and actual dissuading of patients from taking an effective and safe drug that could save their life. And and this has been this has been reinforced to where we’re in a situation now where social media and journalism have more of a say in what people believe than their doctor.
And there’s been a very quite dramatic acceptance among the journalists that rebound is a real thing and it’s a bad thing. And as we heard today, we don’t have evidence that it’s either of those. And that’s just an editorial comment.
JOHN TRIZZINO, NOVAVAX
[00:12:40]
Ultimately, right, there has to be a harmonization of strain selection and we will align with what FDA wants in that strain selection process. We will also align and harmonize with what EMA– EMA has already made statements about harmonizing with FDA’s strain selection choices. Again, very similarly what’s done in the flu market.
[00:13:03]
But the working group with FDA is going to give us an opportunity to work closely with them, and see what they’re seeing from a surveillance standpoint, and say, here’s maybe, let’s call it, four vaccine candidates that we’ll take through that entire process and actually have manufactured some product at large scale manufacturing, so that when that decision is made, we can align with FDA and we’ll have made our best bet on what those strains would be based upon that ongoing conversation and working group with FDA.
[00:13:33]
So the goal is we will be aligned in the fall campaign with whatever those regulatory authorities are choosing the strain to be included.
…
QUESTION
[00:17:14]
And can you talk about the gating factors in terms of that full BLA approval and submission? What has been the reason for the delay?
JOHN TRIZZINO, NOVAVAX
[00:17:23]
So it’s an accumulation of data, right? So it’s not just the phase three that were completed and complete kind of clinical study reports that have to be finalized. But there was some ongoing work that was done, post some of those trials, that are being included in the package. So it’s really getting the full data set together, the full safety data set, the full out reports, and compiling all of that, and publishing all that, and making sure that that’s a complete data set for them to have and review the BLA.
QUESTION
[00:17:52]
And would you characterize that the remaining factors are mostly clinical data related? Or do you feel like manufacturing, there’s still some concerns?
JOHN TRIZZINO, NOVAVAX
[00:18:00]
No, no, it’s just having the complete data set.
…
JOHN TRIZZINO, NOVAVAX
[00:23:01]
So we have nine months of dating of the product today, expecting to expand that to 12 months. We don’t have that yet, but we expect to have up to 12 months of expiry. So I think it’s more than sufficient enough to, if you look at that season and durability of protection, of when you’re going to vaccinate.
[00:23:22]
So expiry is one thing. So stability of the product, and then you’ve got durability of protection, so you want to be able to vaccinate through the season and then have a sufficiently long time of durability of protection once vaccinated.
…
QUESTION
[00:29:12]
Do you have any kind of like rough sense of of when would be the earliest that you can see that, a product going to market?
JOHN TRIZZINO, NOVAVAX
[00:29:18]
Hard to say. Because you got to come out of that and then you got to go into an efficacy trial. I think at this point, it’s not just going to be immunogenicity that’s going to win the day. I think you’re going to have to show the efficacy of the combination.
Question
“4) For quadrivalent 2023-2024 influenza vaccines in the U.S., does the committee recommend inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the 2nd influenza B strain in the vaccine”
Yes Votes
No Votes
Abstain Votes
HENRY BERNSTEIN, VRBPAC
[00:25:58]
It seems that B Yamagata lineage has not had a prominent role. Has there ever been quadrivalent influenza vaccine, is it even possible, where there would might be three A strains and one B strain? Rather than two As and two Bs?
JERRY WEIR, FDA
[00:26:18]
No, the reason is because quadrivalent vaccines, as they’re licensed, are for a H1N1 and H3N2, a B Victoria and a B Yamagata strain. That’s the way the licenses are set up.
[00:26:35]
When the quadrivalents were licensed, we had to have data showing that the inclusion of that fourth strain did not adversely affect the vaccine performance or the quality of the vaccine. Similarly, if there were a change to induce something else, like occasionally it gets thrown around, could it be two H1N1 components or it could be two H3N2?
[00:27:03]
There would have to be, first of all, recommendation for that. But second of all, each manufacturer would have to amend their license to make sure that that was permissible. In other words, they would have to have data to support that. So we can’t just make such a recommendation. It would involve a license change for each of the manufacturers.
…
ARCHANA CHATTERJEE, VRBPAC
[00:53:03]
But I was just curious if there are maybe other sources of data for these questions. The first is whether we have vaccine efficacy laid out by the type of vaccine that was used. So high dose adjuvanted versus regular dose vaccines. And the second question is around egg based versus cell based vaccines, whether there’s any difference noted in the VE based on those.
LISA GROHSKOPF, CDC
[00:53:33]
At present we don’t. Confirmation of vaccines received is something that occurs through the spring into the summer. There are times when there is enough information at the very end of the season when the final estimates are being prepared for publication where there are enough data.
[00:53:50]
But as of right now, no.
[00:53:53]
One limitation of this is that in general, the networks that – the sites that participated in these networks aren’t dictated which vaccine to use. So we tend to not, sometimes, have very as high uptake of some vaccines compared with others.
[00:54:11]
There is actually one extra slide I have that shows– if it is possible to bring up the slide deck and if you’d like to see that, that shows what the relative utility of the use at least in one of the networks was. But essentially what I can say is, we don’t have information yet, for example, on high dose versus adjuvanted.
[00:54:32]
We have not had, in general, appreciable uptake of LAIV in recent seasons to be able to do LAIV independent estimates. There’s been overall less use, for example, of recombinant than of the other vaccines so far. So at this point, we definitely don’t have that data.
[00:54:51]
It’s possible that some might come later when we have a better sense of vaccine use, but it’s hard to predict how that will go at this juncture.
…
DAVID WENTWORTH, CDC
[01:56:20]
This is a real challenging situation because there’s a few things that we need to consider there.
[01:56:29]
There hasn’t been a strong influenza B season since SARS emerged. So we really haven’t had like a very large influenza B season. And so that’s one of the things. So time is a piece of the factors. Unfortunately, it’s going to take time.
[01:56:47]
But as Dr. Jerry Weir pointed out, there’s no vaccine that you could put two H3s in that’s licensed yet. So, I mean, I think there are two separate questions. I really I think it’s laudatory to think about new vaccines that would improve the effectiveness of protecting people from infection and serious disease, etc. So that’s a good opportunity. But with B Yamagata, there’s that piece of the puzzle.
[01:57:15]
One of the things I pointed out at the last VRBPAC, when we got into B Yamagata discussion, was if you looked at H1s, we didn’t detect any 5A1 viruses for quite a while. And then once SARS subsided a bit more and we got into later stages of the pandemic, we saw that virus come back, and it looked a little bit like it was gone.
[01:57:36]
So there has to be a more concerted effort, and we’ve been trying to really support all the GISRS labs to do more lineage typing. So there’s still too many viruses that go just as typed as B, but they aren’t lineage subtyped, because that’s an extra test that has to be done. And so we’d like to see a lot more data in that space as well. So it’s kind of a combination of time.
[01:58:03]
And then the third element that will be discussed at some point in time with within at least the WHO community is what is the real risk that B Yamagata would represent, even if you can’t declare it extinct yet, what’s its risk level? And so that’s, I think, a thing that you might be driving at as well.
…
DAVID WENTWORTH, CDC
[02:02:03]
When we are selecting egg based vaccines, we are looking at those that have the least antigenic impact. So amongst all the egg isolates, we look to see which ones react most like cell isolates, right? And so that’s part of the analysis that down selects various egg prototypes from being nominated.
[02:02:24]
Now, as you clearly identified, H3 is the most challenging. It’s very human adapted to the human 26 receptors and it does not grow as well in eggs, which have these sialic acid with a 23 linkage to galactose. And so it generally has to undergo two to three substitutions, rather than just one, in order to replicate efficiently in eggs.
[02:02:50]
And so that’s why even with the ferret antisera I showed you with the Darwin 9, which has a pretty good phenotype as an egg virus, we do see some more subtle reductions that push it beyond four fold reduced from the two fold that we would see with the Darwin 6 like system.
[02:03:08]
The various new vaccine platforms can address this issue and it does to me look like it could potentially help with match. But there’s other factors that I think Dr. Grohskopf kind of alluded to in the real world setting that I don’t think we fully appreciate. When we get down into the real nitty gritty and granular using a ferret, you see one thing and it may not be as reproducible in humans where you get a broader response and whatnot.
[02:03:35]
And part of it to me also is the magnitude of the response you get. So you could have a perfect antigen with a low magnitude response. It still won’t protect you very well as an imperfect antigen with a very large magnitude response. And I think that– I’m not sure how that differs between the different platforms other than with the Flublok, it has 45 micrograms of antigen in it. So it’s basically similar to a high dose egg based vaccine where that has 45 micrograms instead of 15 that’s required to be in the Flucelvax and regular inactivated egg based vaccines.
[02:04:13]
So I think it’s, like I’ve said with other things, it’s kind of complicated by the different styles of platforms. But the true issue for us is when we isolate viruses in eggs, which is required to propagate it, and that for that platform, it almost always has to change. And the changes tend to be more subtle in the H1s and the Bs.
…
JERRY WEIR, FDA
[02:17:11]
I think any sort of move toward a different composition than what we have now really does need to be globally coordinated somehow. And so it probably should start with, and again, I’m not trying to pass the buck, but I really do think this should probably start with discussions at the WHO for how globally manufacturers would respond to a change in environment where really one does not have a B Yamagata and where one might could do something else that is more in the interest of public health.
[02:17:46]
So of course, this committee is free to make suggestions on what they think should happen. We would welcome those. But I do really think that this is a global issue that needs to be addressed and probably a push from the WHO as well as individual countries to encourage manufacturers to generate data that could be considered by the WHO as well the VRBPAC in future meetings that would support some different composition that might be advantageous from a public health point of view.
[02:18:25]
I don’t know if that answered your question or not, but again, I don’t think we’re missing anything here. I think we’ve noticed this, others have. And my impression is, from talking to the the chair of the VCM of the most recent one, is that the WHO does intend to address some of these issues over the next year or so. At least, that’s what I was told, and I hope that’s the case.
…
DAVID WENTWORTH, CDC
[02:19:23]
I think I’ll just state scientifically that it’s easy to think two H3s would be a good thing. So we’ll use H3 as an example. We’ve got two diverging clades that are both happening. And what I showed you was Darwin 6 antisera covers both those clades better than either of those clades cover themselves, then either of those clades cover the other one, right? So they’re diverging from a point and they’re closer to that point that they’re diverging from than they are to each other, antigenically.
[02:19:56]
So one could consider let’s put both of those in the vaccine. And in some ways that might work at say, for example, position 140, where they have convergent or parallel evolution and they both have– and that’s in site SA, site NA, and so then for that particular epitope, it would almost be a good thing to have double the amount. And then– but a lot of people think, so when there’s often we have non parallel evolution happening, so just diverging evolution, that if you put both those in the vaccine, it may not give you the prime against both of those antigens, and that’s what needs to be tested in animal models and humans to me, because what it could do is highlight the conserved epitopes between both those, that is basically double the amount, and so you create immunodominance not at the place that’s under the strongest evolution, you create immunodominance where there’s conservation. And that may be fine, that may be a great thing, or it may be a negative.
…
JERRY WEIR, FDA
[00:14:26]
Generally, we put these out as a starting point. And if the committee should vote no, then I think the committee would have to come up with an option, a proposal for something else to vote on. Might not be that easy, but I think that would be how it would have to work, because again, these are licensed vaccines with four components and it’s our job to select something. So I think it would be incumbent upon you, the rest of the committee that voted no, to offer an alternative.Like I said, we usually do this, and we just assume we would deal with it if that happens.
…
ELISABETH NEUMEIER, GSK
[00:24:41]
So the development of a quadrivalent vaccine with a different composition than the licensed one is a development project, similar to the move from trivalent to quadrivalent. So I think I can say that the development will not interfere with commercial production and provision of the volumes that are required both in the U.S. market and globally.
[00:25:14]
If we speak about– if I understood your question right, it was primarily about development, but potentially also about different vaccine compositions in the market? That would be a real challenge. Because in that case we would have to produce not only four, but potentially five or more components. So I can’t I cannot speculate on those scenarios, but that would be a real challenge, if not impossible.
…
JERRY WEIR, FDA
[00:35:50]
The downside, of course, is that the lack of certainty that that strain of B Yamagata really no longer exists. And, you just saw some of the slides that said that only a very small proportion of the B isolates were really typed. So there is some downside to taking it out too early. I think that was your primary question.
[00:36:18]
The other downside of taking it out is that, and I kind of stressed this earlier, I think if it’s going to be, okay, so from a regulatory point of view, it can be taken out. That part is not actually hard because manufacturers are licensed to produce trivalent or quadrivalent.
[00:36:36]
The real issue is coordination, though. I don’t think you’re going to see one manufacturer just decide to take it out by themselves because then they will say, well, how does this play in the public? How is this going to be marketed when everybody else keeps four? So that’s back to the whole issue of, if it’s going to be taken out, it probably needs to be coordinated globally just for, otherwise, it’s just not going to happen. Regulatory wise, yes, we can deal with it. That’s not a problem.
[00:37:07]
I think we’ve already discussed, though, besides the issue of taking it out, there is the issue of coming up with a different composition. And that’s the one we’ve mentioned several times, that there’s just got to be some more data generated so that we don’t basically do something wrong with the vaccine and actually have something that doesn’t work as well. And I think Elisabeth mentioned the fact, some of the details about, in the development work, there are some issues that that can only be solved by developmental research and that’s coming up with potency reagents for two things that are very closely related, coming up with serology reagents for two things that are closely related.
[00:37:49]
It’s not that those are insurmountable. That just takes some work. I may have covered most of it, but looks like David can also chime in here.
…
JERRY WEIR, FDA
[00:38:44]
I think you’re probably right. And when I talked to Dr. Subbarao, who was also, I think, the chairman of the VCM this particular time, I talked to her last week, she indicated pretty strongly to me that the WHO intended over the next year to have meetings both with interested stakeholders that included manufacturers to just address these type of issues around the B Yamagata. When is it going to be– when is everyone going to be comfortable that it no longer exists? Is there more data that we need to be to get to that point?
[00:39:20]
So I did get the strong impression from her that there were going to be follow ups this year by WHO to address this issue.
…
DAVID WENTWORTH, CDC
[00:39:34]
So there’s a goal to do some follow ups. There’s a goal to do some targeted work in the younger age group in particular, because they would be likely the most susceptible based on population serology type work. But that is also the risk. It’s to that that age group, wouldn’t have any prior infection history with Yamagata like viruses, they wouldn’t be– so, for example, you know, if we went to a trivalent that had B Victoria, you do get some boosting of B Yamagata responses in older people, but you wouldn’t see that in that very young population. It would be just like my answer about the 5A1s and 5A2 swith the H1. But it would be more striking because there’s many, many amino acid differences between those two lineages. And so that that’s one of the risks.
[00:40:28]
What’s the benefit is another question that maybe the committee wants to ask themselves, what’s the benefit of removing it if you don’t have something else to switch to?
[00:40:38]
And then I think in the trivalent scenario, probably in the U.S., we’re okay. But I think there may be some challenges to moving to trivalent in Europe because I’m not sure their licenses are maintained if they’re not continually used.
…
JERRY WEIR, FDA
[00:41:06]
Just remember, back before there were quadrivalents, it was often a real struggle to pick which one of the B lineages to include. And we were essentially wrong about half the time, certainly at least the third of the time. And you could see clinical consequences when that– when that choice was not not well matched. So it’s the cross-reactivity doesn’t save you.
…
ARNOLD MONTO, VRBPAC
[00:46:39]
I’m going to take us back to the Yamagata situation. And I just want to remind us all that, in terms of COVID strain selection, because things were not moving quickly at WHO, the U.S. took the decision to make a different recommendation from the one that was made by the WHO advisory group. I don’t think we should do that here. I think the flu vaccine is a global, some people would say, commodity, and that’s part of the problem, I think, without moving towards identifying our discomfort with the fact that we’ve gone for several years– granted, we have had the pandemic and everybody has been busy with other things, that we really haven’t looked towards some of the solutions to increase VE by including additional strains or even more of the H3N2 in a trivalent vaccine.
[00:48:11]
And I feel very uncomfortable at this point in continuing to recommend a B Yamagata strain, I’m not going to go as far as no, but I will abstain because I don’t feel comfortable in continuing to ignore what looks like a situation where B Yamagata is no longer circulating and we’re not really trying to figure out what we should do to at least use the same antigenic weight that we have in the current vaccine of 15 micrograms times four to improve vaccine effectiveness.
[00:49:04]
We really need to send a message and I’m not so sure that’s done if it’s only private conversation that indicate that something may be brewing because it needs to include the manufacturers as well.
…
DAVID WENTWORTH, CDC
[00:51:14]
So I think, number one, I’d comment to Dr. Monto. I actually agree that we really need to be moving forward and to see what we can do because it takes a long time to license something new. And so I’m in complete agreement with that.
[00:51:29]
I would say that I think the question here is, which it’s, you know, it’s a licensed product for a quadrivalent vaccine that has a B Yamagata component. So the question is really, do you put Phuket in it or what else do you put in it? So to me, that’s more of an FDA point. But to me, that’s the way I read these questions.
[00:51:47]
And then to the crystal ball piece, it entirely depends upon what kind of Yamagata re-emerges, if one does. So there was some very odd looking B Yamagata viruses in the Netherlands prior to its not being isolated anymore, really antigenically distinct. And so if something like that were to reemerge and be fairly fit, it could move through our population in the same, I would guess, the same speed with which the triple deletion B Victoria viruses moved through our population, which was within about six months it was a sweep to that whole strain. So that’s kind of one vaccine cycle.
[00:52:26]
Now, depending on when that catches us in the vaccine cycle, that could be very bad or it could be not very bad at all. If it’s if it looks a lot like the viruses that we saw in 2019 that were kind of the run of the mill, they were very B Phuket-like antigenically, even though they were quite old, a few years since that virus was isolated, then I think they would move relatively slowly, and you would have this kind of petering, with years time. And so I think it really depends on what emerges.
[00:53:02]
But I don’t think it’s out of the realm of possibility that something antigenically quite distinct could emerge. I mean, that’s really what you saw with H3 through the COVID bottleneck. You know, something quite distinct eventually kind of really took hold.
…
ADAM BERGER, VRBPAC
[01:23:50]
I’m going to skip my my votes for questions one through three. I think those are self-explanatory as to why those are needed components of the vaccine.
[01:24:00]
So I’ll say I voted no on the last question around the inclusion of B Yamagata for the same reason I voted no in the last meeting. The inclusion of a strain that’s not circulating doesn’t seem to offer additional protections for the public.
[01:24:14]
And this isn’t a vote against continuing the currently licensed quadrivalent. But at this point, I think we really need to send a strong signal that in the interest of public health, we need to be conducting the studies to generate the evidence base for a much more flexible vaccine composition now. So that’s the reason why I voted no.
…
AMANDA COHN, CDC
[01:24:46]
I voted yes for the fourth vote to include B Yamagata because, even though I completely agree with Dr. Berger’s points, I did have concerns about what would happen to the quadrivalent vaccine and the program if we didn’t have a usable vaccine for this year. And so in the spirit of ensuring that we had accessible choices of vaccines while we continue to move forward with improving the strains that are in there, I voted yes.
…
HANA EL SAHLY, VRBPAC (CHAIR)
[01:40:40]
I abstained from voting on the inclusion of B Yamagata. I hesitated between no and an abstain, but it’s definitely not a yes.
[01:40:49]
Influenza virus is not known to be shy. If Yamagata was going to circulate in the last four years, we would have picked it up. We do note that the trend preceded the pandemic, and we indicated for, I think, two or three meetings now that, well, the non-pharmacological measures of the pandemic are going over. We’re seeing a whole lot of flu, but we’re not seeing B Yamagata. We said we’d give it one more season. The season was this year, and we had really an abundant circulation of of flu all over the world, and Yamagata did not rear its head.
[01:41:28]
When and if it does, we’d be ready. From a regulatory standpoint, going from four to three shouldn’t be a hurdle because there is a trivalent vaccine, and no additional research or developmental work needs to happen for us not to include B Yamagata. And when it comes to implementation and vaccine distribution, also not including B Yamagata should not impact our ability to distribute the vaccine to those who need it each year.
[01:42:05]
So that’s that’s why I chose not to vote for B Yamagata this year.
QUESTION
[00:20:50]
Tell us why a baby should get the– or the mom should get the vaccine and not the baby get nirsevimab?
ANNALIESA ANDERSON, PFIZER
[00:20:57]
So, maternal vaccines are a perfect example of how nature works in the fact that the mother transfers her antibodies to the baby, it’s called the mother’s gift, in the late stage of pregnancy. And so the baby is born with the same level of circulating antibodies as the mom has. So if the mom hasn’t been exposed to a pathogen, she won’t have the antibodies. But if you vaccinate her, she does.
[00:21:25]
And why is that important? So, a baby is susceptible to RSV from the first breath, when you have your new baby even in hospital, as you’ve got people coming to visit, especially young siblings, an RSV infection happens very, very quickly. It’s not something that kind of takes time to develop. You will come into contact with someone with RSV and you will become infected. And newborn babies are particularly vulnerable to the severe outcomes. They can’t tell you that they’re having difficulty to breathe often. Yeah? It takes an expert to be able to measure what’s going on and be able to say, yes, your baby is in severe distress, at which time it’s then hospitalized.
[00:22:11]
And so we think that there’s real medical value in having a baby protected really from, as I mentioned, the outset from that first breath.
QUESTION
[00:22:22]
And this gets back to adult RSV vaccines. But would you like us to contemplate a situation where Pfizer gets a preferential recommendation from ACIP?
ANNALIESA ANDERSON, PFIZER
[00:22:33]
For ACIP recommendation, it’s very rare that you see preferential recommendations for vaccines that should have clear medical benefit. And so from our perspective, we’ve had a couple of interactions with the ACIP more recently, in two weeks ago, where they’ve been very positive about our vaccine, and we haven’t seen any indication for the potential of preferential recommendations at this time.
ANGELA HWANG, PFIZER
[00:23:02]
Steve I agree with with Lisa, but I think that when we think about what else you need beyond the clinical profile to have a successful vaccine, I would say that both RSV, adult and maternal really fall into the sweet spot of what Pfizer does. Think about our leadership and the capabilities we have in adult respiratory diseases, both vaccine and treatment. You know, began with what we had in Prevnar and then further reinforced by the tremendous successes and the strength we have in the market from Comirnaty and Paxlovid.
[00:23:33]
I mean, the primary care setting, the retail setting, urgent care, just every primary care and community setting that you can imagine is a stronghold for Pfizer, that’s one. You think about pediatrics, think about women’s health again, areas of great strength for Pfizer.
[00:23:52]
So I think what we have is a combination of a great vaccine, but also incredible commercial capabilities that are already well established and an engine that’s already functioning that we can put both of these vaccines into.
…
ANNALIESA ANDERSON, PFIZER
[00:28:07]
So we started a flu program with mRNA in before the COVID pandemic, really with an eye to have better flu vaccines. And so currently flu vaccines, between 40 and 60% efficacious every year, even worse for older adults. This year, the efficacy for older adults was 35%. And so knowing that, we felt that we could do much better, and the issues behind why those vaccines aren’t very good include the fact that there’s a long lead time to picking which strain is going to cause disease. And they’re often wrong, or the strain will change during the season, and also many of the vaccines are made in eggs. And this means that you’re making a vaccine that would recognize a chicken egg virus, but not necessarily how the virus behaves when it infects you. And so that was our first goal, was really to develop better flu vaccines.
[00:29:05]
Then COVID came along and so we switched our work on our RNA with flu and moved over to COVID in partnership with BioNTech. And, you know the story there. So now as we look forward, you know, we’re looking towards, and we’re predicting that, we’re going to have at least annual COVID vaccinations. And so, how many vaccines do people want to take? And really, we see for adult vaccines, as that we saw with pediatric vaccines, is the future really is going to be in combinations, particularly for these annual vaccines that are going to involve strain changes.
[00:29:47]
So, working with, we currently have our efficacy program for the monovalent flu vaccine ongoing. We expect it to read out later this year. But we’ve also started early work on a flu COVID combination vaccine, which is, as Angela said, not predicted in the box, but something that will be coming forward.
STEPHEN HOGE, MODERNA [00:05:36]
I think the science supports a bivalent approach and we’ve seen that in our own data, in public health officials data. We ran actually a head-to-head clinical trial of bivalent versus monovalent last year in the United Kingdom and showed against some of the earlier Omicron strains significant improvements in efficacy in preventing COVID 19.
[00:05:56]
Now, again, it’s really not our choice alone. We have to be prepared for all outcomes, and that’s one where we will look to guidance from public health, particularly the FDA, but also CDC, on which choice they make for this coming year, whether it’s a monovalent or a bivalent to move forward.
[00:06:13]
I think from the data I’ve seen so far, I think a bivalent covered more bases.
…
STEPHEN HOGE, MODERNA
[00:18:00]
So from our perspective, heavy focus on this first generation product is get it approved, and show public health that we can update later in the season, and have better matching, and avoid those mismatch years, and essentially, even if we’re no better on efficacy, create more value for the health care system.
[00:18:19]
Now the question of where we’re going to show that? I think for now is we’re going to probably do a bit of both. So we are always going to have real world effectiveness studies that look at how the vaccine performs. The CDC will do those as well, and those are going to be really important. And so every year vaccines get rolled out, a better matched vaccine would show better effectiveness in that data as monitored by public health officials, CDC in particular, and then that would provide obviously, publication evidence.
[00:18:44]
But we will probably also take the opportunity in a mismatch year to consider looking at efficacy, because again, it will be the difference between getting a functioning vaccine and nothing and the opportunity to run a efficacy study. It’s not a huge effort when, you know, your your your comparator, the approved vaccine, the other competitive flu vaccines are mismatched. And so it’ll will make that decision at that time. It’ll kind of also on what else we got going on but I think we will look at to demonstrate that potential and then ultimately get credit for that.
…
STEPHEN HOGE, MODERNA
[00:20:27]
But we think technologically that’s that’s possible. And so the single dose form is the first step.
[00:20:33]
Refrigerated, we are also working on. That’s more of a second generation improvement for all of those. It will be easier for flu and RSV than it was for COVID. COVID is an incredibly large mRNA, as we all know, making spike protein, which is a very, very large protein, and that really dictates a lot of our shelf life. And so it’s much easier for us, in some of the newer vaccines.
[00:20:56]
And as I –as I think we announced recently with our 1283, our second generation COVID vaccine, and generations get a little confusing these days, that is targeting actually a refrigerated storage form. And so even COVID, we have to move to that space in the coming year or two.
…
STEPHEN HOGE, MODERNA
[00:23:07]
Our strategy is pretty clearly we’re going to go get the individual pathogen vaccines approved, and those are the ones where you have to run efficacy studies, like large safety and efficacy studies that cost a lot of money, involves tens of thousands – we recruited 75,000 people last year.
[00:23:23]
But then as you move out of those approvals, what you then go start doing is the combination studies. The combination studies are noninferior immunogenicity and safety studies. You just put them together and you pick your final two and you create that combination. And it’s much quicker. It’s again, think of it as the difference between the bivalent updates or the sequence updates we did last year versus first approvals. And then, and that will go really quickly, because you don’t need to go, generally, we don’t expect that we need to go run efficacy studies with the vaccines. We’ve got the efficacy. We’re just showing combination noninterference, good safety, and you go.
[00:23:59]
There is a contingency, though, which is that you have to get the combination of the individuals approved. And so we’re obviously there with COVID. We are optimistic on RSV. Got a little bit of work to do with flu. We’re going to get there hopefully quickly. And then once those are approved, we can do those combos.
[00:24:14]
We are starting the research and development now, so we’re running clinical studies on a range of different combos, because we can answer some of those questions at risk. But if there are small changes to what we’re doing on the individuals, we want to reflect those in the final phase three studies that we run for.
[00:24:28]
So it is contingent on getting those– our focus on getting those first generation monos approved, we’re working our way through the big three very quickly here, and then we will go very fast. Like think of what we did with the COVID updates on the combos and then roll those out shortly thereafter.
[00:24:46]
And so we’re prepared most of that work and I don’t have an update on today, but we’re we’re ready to go as soon as we get them on.
“Phenylephrine has been used safely and effectively as a nasal decongestant by American families for generations, and FDA regulations recognize it as safe and effective. CHPA members continue to follow these regulations. We acknowledge FDA can reevaluate the efficacy of active ingredients – as it is here.”
STEVEN STACK, KENTUCKY
[00:25:47]
The individual attended a large gathering at Asbury University on February 18th that also made the news while they were contagious. It’s estimated that thousands of people attended the gathering on this date from across Kentucky and other states and even from around the world.
[00:26:03]
And so I want to say, first off, we are very grateful to Asbury University, the Jessamine County Health Department, and the Centers for Disease Control, have all been wonderful partners. And again, these are difficult situations to navigate sometimes and Asbury has been a terrific partner, and we’re grateful for that.
…
STEVEN STACK, KENTUCKY
[00:28:32]
If you were at the Asbury event between the dates of, say, February 17 through 20, if you develop a fever, cough, runny nose, irritated eyes and a rash, a red rash on your body, you should isolate at home and you should call your health care provider.
[00:28:47]
Don’t just go show up, unless you are in serious need of emergent medical care. Call them first and say, I think I have measles. Tell them why and they can help you, hopefully, arrange or navigate how to get testing, so you don’t show up in a waiting room and infect everybody else in the waiting room.
JANET WOODCOCK, FDA
[00:07:56]
It was also announced this week that we’ll be moving the cosmetic and colors program out of CFSAN. Now, an interesting anecdote about that is many years ago, when Fred Shank was head of CFSAN and I was the head of CDER and David Kessler was commissioner, there was a desire by CFSAN to transfer cosmetics to the drugs program. And that didn’t go very well, because they really didn’t have any FTEs hardly, they had three FTEs they were interested in transferring, along with the entire cosmetics program. And so that program ended up staying in CFSAN, but it has never been a robust fit with that center.
[00:08:43]
So what was announced is those programs were currently be under the auspices of the chief scientist, Dr. Bumpus. And they’ll be evaluating what to do, including all the new authorities that have been recently given to us as part of the omnibus. So those were the two major organizational announcements that have been discussed.
JEREMY GOLD, CDC
[00:25:51]
There have only been two reports noted to date. The first one was from France. This was probably the the big report that made the biggest splash. This paper came out back in August of 2022. They’re reporting that a dog became infected after living with two men who had mpox. Samples tested positive from lesion material, oral and anal swabs by PCR. However, the CT values were high, indicating a low viral load, but there was quite a bit of sequence data collected as well.
[00:26:19]
However, the authors of this report are now noting that there is no serologic response of this animal as of 26 days post positive PCR test and beyond. And they’re writing an update to their publication that should be released soon. They’re now stating that they believe this is surface contamination coming from the people in the home with mpox, than the animal actually being infected itself.
[00:26:42]
So the other report is coming from Brazil. This is a similar situation where a dog was living in a home with people with mpox and again tested positive by PCR. But we’ve heard from our colleagues in Brazil that this animal also had a high CT value. And no publication has been released yet. We’re hoping more for further information will be available soon.
…
JEREMY GOLD, CDC
[00:30:19]
So a big thank you to all of our partners that that agreed to work with us on this project over the course, D.C. Health, as well as public health departments in Virginia, Minnesota, and Tennessee. Thank you all. I’m sure some of you may be on the call right now.
[00:30:32]
So we were able to sample 34 pets from 19 different households. So not a huge study size here, but definitely some important information that we can study. Next slide, please.
[00:30:48]
So this is a quick summary of the laboratory results, specifically focusing on PCR at this point.
[00:30:54]
So we tested many different animal samples. You can see actually we have samples from the actual animals themselves, as well as the environmental samples, which I mentioned earlier, which oftentimes came from animal bedding, food and water bowls, and toys. All of these samples came from 19 different households, as I mentioned previously. All of the– all of the numbers in the table, as well as in the figure below, these are at the individual sample level. So just comparing all different samples.
[00:31:22]
And there was a significant correlation here between the samples that test positive for mpox DNA and samples that show our RNase-P amplification. Now, RNase-P is a human DNA marker. So in this case, we’re trying to directly show that the PCR positivity for mpox was related to the person in the home with mpox rather than the animal actually being infected itself. And we actually see a correlation between the CT values, between the mpox assay, and the RNase-P assay. So further evidence that this is coming from the people and rather than from the animals actually being infected.
[00:31:57]
The final piece of evidence is from the environmental samples. And actually, all five of the animals that tested positive also tested positive with RNase-P assay. And this is added on to further by the fact that, within the households, all five of the households that had positive animals also had positive environmental samples, whereas out of the 14 households that did not have any positive animal samples detected, only one of those households had positive environmental sampling.
[00:32:31]
So we’re looking to analyze this further to have comparisons.
[00:32:34]
We also conducted a questionnaire assessing with a study to try to assess contact between people with animals in the home. So after we wrap up the study here in the next few weeks, we will begin to analyze this data further. And we’ll hope to have something to share more later.
[00:32:48]
I would like to say quickly, though, that we have not had any animal seroconvert through this study. We have not seen any animals develop antibodies over time, in other words, and we have not had any animals confirmed to be infected with mpox here in the United States.
PETER MARKS, FDA
[00:16:54]
The other issue is, can we simplify this vaccine regimen? And this goes to having so many different vials, so many different compositions, and not necessarily always being able to exchange one vaccine for the other. And so we have a goal to try to consolidate vaccine composition. And we believe that significant simplification is possible, because we, based on data that we have, feel that the same COVID-19 vaccine composition, can be used for the primary series and for booster vaccination.
[00:17:27]
We also think that we can come up with a simplified immunization schedule that would apply to all COVID-19 vaccines and that we would have the same vaccine strain composition for all spike based COVID-19 vaccines, which would hopefully allow one to have interchangeability between the different vaccines so that one does not have to have each of the vaccines at each of the different doses to be able to carry out a vaccination campaign.
…
WILLIAM SCHAFFNER, NFID
[00:25:22]
There are several people who’ve said these monovalent vaccines are expiring soon. Will we be able to start using the bivalent vaccine as the primary immunizing vaccine, and when?
PETER MARKS, FDA
[00:25:40]
It is a great question. And I think we will not let people use expired vaccines. So we’re going to have to do something so that we have vaccine to use. Which means that, as people can tell from the dates, it means within the next few months we have to have these new recommendations.
[00:26:02]
And our anticipation is that, prior to the time we have our next strain selection meeting, we will have done this consolidation that needs to occur. We’re working on it as quickly as we can.
[00:26:20]
It is technically, from the backend, somewhat complicated, but I would expect it in the not too distant future. I wouldn’t wait– it’s not going to come next week, but it’s also not going to be next fall either. It’s going to be– we’re looking at a matter of weeks to, at most, a month or two.
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PETER MARKS, FDA
[00:38:11]
I think there will probably not be the combination vaccine as such this fall. We are hoping to see it, unfortunately, because of the timing of various things, it’s probably too heavy a lift to get that convergence to happen for this fall. I think that had to do with the fact that it was not so clear that annual vaccination against COVID 19 was likely to be necessary, until the past several months. But our goal is for the following season to have that available.
[00:38:52]
That’s not to say that we won’t have data. I think what we are working to do is have a robust grouping of data that will make people feel confident vaccinating people with both vaccines on the same day. People were doing that this year, but we want to have people have even more data to make them feel confident that doing so is both safe and effective. And so we are working, getting real world evidence right now, to be able to support that.
[00:39:25]
But as I said, it will probably be another year, not this season, but another year after that before we have the true combined vaccines.
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WILLIAM SCHAFFNER, NFID
[00:46:19]
Is there research in the works to update the monoclonal environment? Is there a successor to Evusheld in the works?
PETER MARKS, FDA
[00:46:30]
Indeed, there are successors to the monoclonals that are in the process of being updated so that they will get the next generation of variants. And I expect, again, we’ll see– we’ll hear more about those in the coming few months. Obviously, there is a matter of some urgency there because, for immunocompromised individuals, it would be nice to have something to put in that place because, even though we have the antivirals, they are less than perfect.
. . .
BISHOY RIZKALLA, GSK [09:30:38] Almost 32,000 adults were evaluated in the clinical program, with more than 15,000 exposed to the vaccine. Our vaccine demonstrated an efficacy of 82.6% in the prevention of RSV associated low respiratory tract disease in adults 60 years and older. [09:31:00] A high level of protection was observed consistently over an entire season, regardless of RSV disease severity, advancing age, presence of co-morbidities, and RSV A and RSV B subtypes. [09:31:17] The RSV vaccine was well-tolerated with an acceptable safety profile.
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BISHOY RIZKALLA, GSK [09:40:13] Although a correlate of disease remains to be established, age related decline in RSV specific T-cell and functional antibody responses are considered to be associated with a higher risk of RSV disease severity. [09:40:30] On this basis, we have designed our vaccine for RSV in older adults with the aim to potently boost both the functional RSV neutralizing antibody responses and the RSVPreF specific T cell responses. [09:40:48] To achieve this, our vaccine candidate is a combination of a recombinant purified antigen with an adjuvant system.
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BISHOY RIZKALLA, GSK [09:58:33] The primary objective of the study was to demonstrate non-inferiority of coadministration compared to each vaccine being administered alone with respect to the influenza hemagglutinin response and RSV neutralizing titers. [09:58:50] Non-inferiority of the co-administration of RSV and influenza vaccine was demonstrated. For influenza and RSV responses, the upper limit of the two sided 95% confidence interval on the GMT ratio, that is sequential administration versus coadministration group, was below 1.5. [09:59:14] As illustrated on the graph, these criteria were met and showed that the RSV vaccine can be coadministered with a licensed quadrivalent influenza vaccine. [09:59:27] It is important to note there are there are two additional studies ongoing to demonstrate the coadministration of the RSV vaccine with high dose flu vaccine and with the adjuvanted flu vaccine. We anticipate results in the coming months from these studies.
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PEGGY WEBSTER, GSK [10:13:53] In summary, the available safety data in more than 15,000 vaccine recipients showed that a single dose of the RSV vaccine is well-tolerated with a clinically acceptable safety profile in adults 60 years and older. [10:14:11] The reactogenicity profile is well characterized with administration site and systemic adverse events reported at a higher rate in the RSV vaccine group. The majority of these events were mild to moderate in severity and of short duration. [10:14:28] Overall medically attended adverse events, SAEs, PIMDs, and deaths were balanced between groups with no clustering of events. [10:14:40] And enhanced pharmacovigilance activities are in place to further characterize reported events of atrial fibrillation and PIMDs.
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HENRY BERNSTEIN, VRBPAC [10:22:17] I believe I understood you to say that the adjuvant that’s being used in the vaccine is the same that’s in Shingrix, but half the amount?
BISHOY RIZKALLA, GSK [10:22:27] Exactly. Correct. Yes.
HENRY BERNSTEIN, VRBPAC [10:22:29] Can you summarize the experience of that adjuvant in Shingrix and what you’re seeing in the studies using the Arexvy?
BISHOY RIZKALLA, GSK [10:22:43] So the experience with shingles has been established with over 80 million doses distributed and used in this older adult population. It’s first been made available in 2017 and with really compelling efficacy that has been demonstrated and has since been demonstrated to have ten years of duration of protection with this adjuvanted vaccine for older adults to prevent shingles complications. So very extensive experience and a well-established safety profile having had more than 80 million doses distributed. [10:23:25] Now we contain specifically 25 micrograms of each of the immunostimulants. The shingles AS01B vaccine has 50 of each of– so 25 MPL and 25 QS-21.
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BISHOY RIZKALLA, GSK [10:30:00] So what we’ve been able to demonstrate through this final analysis of season one, which will support the licensure, is efficacy of the vaccine over one entire RSV season. [10:30:11] Now, important questions that will be answered from season two and season three of the study. I’ll talk through on design of the study. [10:30:22] So those that received the vaccine in the first season will be re-randomized to either receive placebo or to receive the RSV vaccine each year. So in those participants that receive placebo in season two and season three, we’re looking at the persistence of efficacy of that single dose over the three RSV seasons. [10:30:45] But we’ll also be able to establish the efficacy of annual vaccination as well through this randomization in season two and season three is a very important element of the design of our study.
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BISHOY RIZKALLA, GSK [10:32:19] So this is a plan study for us. We’re in advanced stages of planning for that COVID and RSV coadministration study. [10:32:28] There is a study that has been done with an AS01 containing vaccine with an mRNA vaccine that has demonstrated non-inferiority in terms of the immune response and equivalent reactogenicity. So that was looking at shingles vaccine with a mRNA COVID vaccine. [10:32:49] But this is a priority and definitely it will go beyond COVID. So all RSV vaccines for this age are being prioritized to support programmatic implementation of this vaccine.
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NICHOLAS GEAGAN, FDA [11:15:10] Post-vaccination, a numerical imbalance was observed for events of atrial fibrillation in study 006. An FDA review of these events is ongoing. [11:15:20] The frequency of SAEs [serious adverse events] reported up to six months post-vaccination was 4.0% and 4.5% in the vaccine or placebo groups respectively. In both study groups, most of the assays were events coming to the older adult population and are associated with underlying medical conditions. [11:15:38] One SAE of Guillain-Barre syndrome that occurred nine days after RSVPreF3 vaccination, also categorized as a pIMD [potential immune mediated disease], was considered by the study investigator and FDA to be related to study vaccination. [11:15:52] One death due to acute disseminated encephalomyelitis occurred in a participant 22 days after receiving concomitant RSVPreF3 and seasonal influenza vaccine, was considered by the FDA as possibly related to flu or RSVPreF3 vaccination. [11:16:09] Up to the time of it the data lock point, at least one pMID was reported by 0.4% and 0.3% of vaccine and placebo recipients, respectively. [11:16:19] Two pMIDs, the two cases of ADEM [acute disseminated encephalomyelitis] in concomitant vaccine study 007 were considered by FDA to be possibly related to flu or RSVPreF3 vaccination. [11:16:33] A safety update was submitted for extended safety follow up at month six through 12 containing SAE and pMID data and FDA review of these data are ongoing at the time of this presentation.
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JOE TOERNER, FDA
There were a number of questions this morning about our choice of the word effectiveness in the question. I just wanted to provide a little more context as to why we used that word.
Since 1962, FDA’s been charged with making sure vaccines are safe and effective for use and over the years the statutory regulations have characterized what is the evidence or what types of evidence can demonstrate that a product is effective. And FDA has issued guidance documents in the past that actually have been updated in 2019, there’s a draft guidance document, describing evidence of effectiveness for NDA and BLA applications.
And so it’s really in the context of an adequate and well controlled trial of vaccine efficacy that we’re asking you to comment on evidence of – is there substantial evidence of effectiveness here that’s been demonstrated. So don’t get too distracted by the choice of that word, it’s just a reflection of how our statutory guidelines are worded and the demonstration of an adequate and well controlled study is providing substantial evidence of effectiveness for a product.
Just wanted to provide that clarification for you all.
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MARIE GRIFFIN, VRBPAC
I think our votes will be considered, these yes votes, as supporting licensure. And I don’t think necessarily everyone who voted yes thinks that the vaccine should be licensed at this point. So I just want to say that, yeah, I think it’s a great study. I think the sponsor did a great job. I would be comfortable with more data, more years of data.
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AMANDA COHN, CDC
Nothing more to add in terms of my rationale for the vote. I agree with the other comments.
The impact of this vaccine will be – will only be seen when we achieve high uptake and I think if you look over, if you think about this over many years, it may be that having more robust data from additional – that we will be getting soon – may in the long run actually be better for public health than getting this vaccine out during this season.
I think we are seeing what happens with adult vaccines which are really really hard to disentangle the risks and benefits in a population that is not all uniformly healthy like we see in most children and infants. So I think this whole meeting has given me pause and hope that people really come together and think about how in the future these vaccine studies can be done so that we can disentangle some of the stuff early and make sure that we do maintain high vaccine confidence in the population.
CDC is aware of a confirmed case of measles in an unvaccinated and contagious individual who attended a large religious gathering in Kentucky on February 17 and 18. Large numbers of people that attended the gathering from across Kentucky and from other states and countries may have been exposed. An estimated 20,000 people attended the gathering on the days that the patient attended. The Kentucky Department for Public Health is actively working with CDC and clinicians to help identify if there are additional cases.
To prevent further spread, CDC recommends that clinicians continue to be on high alert for measles symptoms among those who may have attended this event, as well as symptoms in unvaccinated international travelers.
Community transmission of measles in connection with this event is possible, particularly among unvaccinated or under-vaccinated individuals. Everyone should make sure they are up to date on the MMR (measles mumps rubella) vaccine. Two doses of MMR vaccine are about 97% effective at preventing measles if exposed to the virus. Unvaccinated people who may have been exposed at the Asbury University gathering are encouraged to call their medical provider and get vaccinated.
CDC recommends that all U.S. residents six months of age and older that are traveling abroad be fully protected from measles and receive the MMR vaccine, if needed, prior to departure. For a list of active measles outbreaks, please visit the CDC Global Measles Outbreaks webpage.
Is CDC aware of any hospitalizations or deaths from XDR shigellosis?
The National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS) does not routinely collect outcome data on cases of antimicrobial resistant shigellosis. However, states sometimes provide CDC with outcome information on cases of shigellosis associated with outbreaks.
Among the 239 cases of XDR shigellosis reported to CDC through February 22, 2023, 148 were associated with an outbreak.
Among the 148 cases of outbreak-related XDR shigellosis with available information, 39% (24/61) lead to hospitalization and 0% (0/63) lead to death.
I see the alert describes increases in XDR shigellosis in MSM. Have there been any reported outside of this demographic?
Multiple reports have described an increase in antimicrobial-resistant Shigella infections have been published among other adult populations, people experiencing homelessness, international travelers, and people living with HIV.
CDC national surveillance data shows that from 2015 through 2022, the greatest number of XDR shigellosis was among adult men and that this trend has steadily increased. Additionally, compared to other demographic groups (adult women, 14.7%; children, 0.4%), the highest proportion of XDR cases are among adult men (85%). These trends are also consistent with recent increases in outbreaks of antimicrobial-resistant shigellosis among MSM.
CDC notes that the spread of XDR Shigella is a global problem. XDR Shigella infection has been detected in places with strong surveillance, including Australia and countries within Europe and Asia.
Several other publications address the topic of groups affected by antimicrobial-resistant Shigella, including: