FDA Provides Latest COVID-19 Updates

[MUSIC PLAYING] Welcome, everyone. You're watching Coronavirus in Context. I'm Dr. John Whyte, Chief Medical Officer at WebMD. Today I'm joined by a very special guest, Dr. Janet Woodcock, the Acting Commissioner of the US Food and Drug Administration. Dr. Woodcock, thanks for joining me again.

Really happy to be with you.

There's been a lot of activity at FDA, especially in the last few weeks. There's been revisions of two emergency use authorizations, one for convalescent plasma-- we recently talked to Dr. Peter Marks about how that has been revised-- but then also one for monoclonal antibodies. And that's when you and I last talked about the use of this therapy. Can you talk about the revised EUA?

Well, a new EUA was issued for a combination of bamlanivimab, which is a monoclonal antibody that first had an EUA from Lilly. And this EUA is for a combination that adds a second monoclonal antibody.

And the reason to do that is to decrease the what are called "escape variants," which would be treatment-emergent virus that comes up during exposure to the antibody. And it's much less probable if you have two different antibodies that recognize two different parts of the virus. So that combination was studied in a large trial in high-risk patients.

And this was based on additional data, as you talked about. And it speaks to sometimes additional data restricts utilization, as it did in convalescent plasma. And here, it could be broadening it, where we're talking about patients with mild to moderate disease, people who are not hospitalized and not on oxygen but are at high risk for problems with COVID.

The challenge has been-- in this therapy, monoclonal antibodies, as you and I have talked about-- is how do we get the information out there? How do we let clinicians and patients know about it given that the US government has purchased over a million doses? Approximately 250,000 have been utilized. Have we made progress in terms of how people can find out about it, how we can create infusion centers? What's the latest on that?

I think a lot of progress has been made. Very soon, we should open up the monoclonal antibodies to direct ordering so they can be ordered by anyone who has the capacity to administer them. And I think that will provide a lot more sites.

But with the publication or the announcement of the results of the last Lilly trial with the combination, where they had a statistically significant impact on hospitalization and death, and they also showed the decreased markedly admission to ICU, I think there'll be a lot more enthusiasm also for using these products because it's been definitively demonstrated what they can do. But as far as getting the word out, really, there's a bottleneck in infusions of people who are highly infectious. Can't use regular infusion centers unless you're willing to sanitize them in between giving them to infected patients and then the usual people who come in who may have cancer or be immunosuppressed.

So we're finding different outlets. People are using creative solutions to get outpatients early as possible, people who are at high risk, get the antibodies into them so they won't progress in their disease.

Dr. Woodcock, we can't discuss the vaccines without discussing the variants and whether the vaccines are effective against the variants. How do we even know that? And what is FDA doing in case we need to have a booster? I understand there'll be an expedited process for that as well.

Well, as far as we know, the vaccines that we have under EUA right now are effective against prevalent variants circulating around the world, although we think there's some diminished efficacy against what is called the South African origin strain. But we think they'll still be effective. However, we have to consider that with the whole world incubating the virus and the virus replicating in so many people, there'll be many mutations arise. And we have to be prepared.

So the FDA is doing-- number one, we're doing scenario planning in case the worst-case scenario would occur and the resistant variant would arise. We're also planning to issue three guidances, one on vaccines and how manufacturers should both surveil for and then could augment their vaccine in case of a variant arising.

One is about diagnostics because, actually, the diagnostic tests could return false negatives against a variant if it were different enough. And that has different parameters for the PCR tests versus the antigen test, which use antibodies and are more susceptible. And then, of course, the therapeutics also could lose efficacy against various variants. And we have a pretty good handle on that. We've been doing a lot of testing on that.

And certainly, some of the monoclonal antibodies could be less effective or lose effectiveness against certain strains. And there's already work to develop additional monoclonals. We have a very good pipeline. And we also have an understanding of which variants will effect which monoclonal antibodies. So we should be issuing those guidances soon.

What does soon mean, a couple of weeks?

I hope so. I would certainly think so. There'll be drafts for public input and comment. And then we'll issue a final guidance. In the meantime, of course, we're talking to individual manufacturers as they begin to do their own scenario planning and think about how they could modify their vaccines or additional therapeutics and so forth if variants become prevalent.

The other big issue for vaccines is relating to children and how soon children might be vaccinated. Is that something that could be possible, a vaccine authorized for children in the new school year? Or are we going to have a lot of different type of trials based on a child's age?

An elementary school student is different than an early high school student. And you've often talked about that kids aren't mini adults. How much work needs to be done before we're at a point where we can be realistically talking about availability of vaccination in children?

Well, there is work ongoing in the adolescent population. And we would expect to get some information about that fairly expeditiously. Younger age groups then would have to be studied and look at the immunogenicity of the vaccines. The virus appears to affect younger children differently.

And I think, traditionally, those children are studied separately from vaccines. So additional work needs to go on for the younger age groups.

Right. I do know they're looking at enrolling kids 12 through 16 and then talking about enrolling children less than 12. But you were the therapeutic lead at Operation Warp Speed. And something that's overlooked is the number of therapeutic agents that are being studied for COVID treatment, whether it's already approved drugs, such as metformin, or new molecular entities. Can you help give our audience the sense of the number of drugs that are being studied for treatment of COVID? It's a vast number, isn't it?

Yes. It's hundreds. We did an inventory as part of our work at FDA and then have maintained that based on the registries around the world, the trial registries. The vast number of agents being studied are repurposed drugs. There are a huge number being studied in patients in the inflammatory stage because we have a large number of anti-inflammatory or immunomodulatory agents. So there's a lot being studied there.

And then there are a huge number of oral repurposed drugs, everything from colchicine to fluvoxamine to ivermectin and so forth, metformin and so on, that are being studied in the outpatient. We're trying to get together a larger pragmatic trial in outpatient so we can study more quickly and definitively.

A problem with a lot of the repurposing studies that are going on is they don't yield definitive data. In fact, we found of all the trial arms going on around the world for therapeutic agents, only 5% of trial arms would actually give us an answer that would be actionable. And this is a huge problem because then we get all this suggestive data. And we don't know what to do with it.

Well, I want to ask you, has COVID changed the way that clinical trials are going to be done in terms of-- you've always been a big proponent of adaptive clinical trial design, master protocols. We're talking about doing clinical trials in the home to improve the number of diverse populations. Do you expect there to be a real change in the way clinical trials are conducted for new drugs?

If I have anything to do with it, there will be. I believe that we need much more community-based research, clinical research. That's how you reach various populations. You can't try to do that at the moment there's an emergency. You have to build that trust and that research infrastructure.

I think we should have clinical trial networks with ongoing study, say, of the chronic diseases that afflict Americans and the best way to treat them as outpatients. And then if we have another emergency like this, we have that infrastructure in place. And it could be rapidly repurposed to study repurposed drugs and get definitive answers. So there's a real opportunity and hope there that we can improve the clinical trial ecosystem as a result of this experience.

Now, you know this. A lot of the pundits are saying that the risk-benefit framework is permanently changed at FDA as a result of the pandemic. Do you think the COVID pandemic is going to have a lasting effect in terms of how the FDA evaluates risks versus benefits?

I don't think so. The benefits and risks haven't changed the way you look at harm and the way you look at effectiveness. The issue with this disease is, in its late stages, it's a mortal disease. And it has tremendous morbidity associated with it as well.

And so under those circumstances, I think as you well know, FDA has long had flexibility in trying to move therapies along versus a new treatment for hypertension or depression or something like that, where the benefit-risk has to be nailed down much more clearly. So I don't think what was done here, especially for EUAs, which overtly have a lower standard-- and the EUA can be withdrawn when the public health emergency is over. So I don't think that FDA has shifted its standards. It simply is responding, I think appropriately, to this tremendous emergency.

And using the authority that it has, such as an emergency use authorization, in a public health emergency. Now, I wanted to ask you about diversity in the vaccine trials. They've done fairly well in terms of enrolling African Americans, enrolling Hispanics. They've done well where others have not. Do you think that'll be a shift as well in terms of stating upfront a commitment to diversity in clinical trials?

Well, I believe, as a part of a movement to really recognize the contributions and needs of all Americans, that this will be highlighted more. I believe, in some ways, the vaccine trials were successful because of the collaboration with NIH and the COVID vaccine network that they have that had made a lot of efforts to have connections and relationships with communities of color in underserved areas. And so that, I think, really assisted in that trust and ability to recruit people of varied backgrounds.

And finally, a lot of people at FDA who work at FDA, who have worked at FDA says it's very hard to please various stakeholders. You either approve a drug too fast, or you approve a drug too slow. What's morale like at the FDA right now?

Well, we've just recently looked at some of the employee viewpoint surveys. And I'm pleased to tell you that morale is, I think, very high. These are public health individuals. And they have stepped up in a crisis. Some of them are just on their knees with work.

But actually, the dedication to the mission, the understanding of how critical FDA is to the management of this pandemic and the work that we do, I think, has kept morale up even in the face of a real crisis. And it has been a very long slog. But morale, I believe, is doing pretty well because people-- that's what they went to school for and sacrificed for so that they could serve their country.

Is there a silver lining in the pandemic?

Well, hopefully there are many things that we can learn. We're mounting formal lessons learned from the US government operation perspective from therapeutics to try and collate all these things we've learned, including about platform trials, but all the barriers that exist to actually getting trials done.

I think that we've all learned, to our surprise, how much we can do remotely. Look at telemedicine. I think that it would completely-- it's going to change medicine quite a bit because things people are reluctant to do or couldn't do or wouldn't do-- all of a sudden, it became possible and actually became pretty routine. So I believe a lot of things are going to change. And many will change in the medical field.

And even back to the issue of clinical trials, the FDA issued a significant amount of regulatory flexibility in the design of trials. And that's likely to stay. Things that we thought were so important, we now realize, actually, there's more gray areas than true black and white. Dr. Woodcock, I want to thank you for taking the time today to update us about the variant, about therapeutics, as well as for all that you've been doing for 30-plus years as a public servant at the FDA and working to keep us all safe. So thank you.

Thank you. Thanks for the opportunity.

And I want to thank you for watching. If you have a question about FDA and COVID or COVID in general, you can email it to us at [email protected], as well as post it on Facebook, Twitter, and Instagram. Thanks for watching.