Coronavirus in Context: FDA Evaluation and Approval of COVID-19 Drugs

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You're watching "Coronavirus in Context." I'm Dr. John Whyte, Chief Medical Officer at WebMD. I'm joined today by Dr. Janet Woodcock. She's the Director of the Center for Drug Evaluation and Research at the US Food and Drug Administration. Dr. Woodcock, thanks for joining me.

Great being here.

Let's start off with, do we know if there are any safe and effective drugs for COVID-19?

No, not yet. There's certainly a lot of people working on it but nothing has been shown, uh, yet to be effective.

And are we undergoing clinical trials for drugs like hydroxychloroquine, remdesivir, convalescent plasma? Ca-, can you give us a sense of where we might be?

Yeah there really are a large number of clinical trials ongoing. The agents that were tried first, such as remdesivir, and, uh, hydroxychloroquine, are, um, you know, fairly far along in development programs. We would expect, uh, a readout from remdesivir, perhaps in the next month or so in clinical trials. And trials for a hydroxychloroquine and, um, chloroquine have started.

And, um, we'll be reading out over the next five months or so in everything from pre-exposure prophylaxis to very ill patients. In the meantime, there are a lot of immuno-, immunomodulators, uh, being tested for the later stages of the disease. And those, uh, should have read out starting, perhaps, at the end of next month and into the summer for the various agents.

And in your mind, when we think about these different treatments-- some are antivirals, some are anti-infectives, some are relating to cytokine storm-- does that tell us about the pathophysiology of the disease? D-, do we know the mechanism of COVID-19 right? What's kind of your thoughts on that?

Well, a lot of this is very speculative. Uh, we know that a large number of people have, um, asymptomatic disease, for example. But other people may rapidly or after a several-week, uh, course of disease, uh, deteriorate seriously, go into an ARDS-like syndrome, and then, perhaps, need mechanical ventilation and experience significant mortality.

And there's still, uh, questions about how much of this is overwhelming virus infection and how much of it is due to, an over-exuberant immune response toward the end of the disease. And the alt--

And even if we're treating it right as, um, you know, an ARDS. It could be more high altitude, as well. There's been a--

Yes.

--lot of discussion about ventilator protocols.

Exactly. So we-- there are so many things we don't know. And that's why there's great interest in doing some, uh, platform trials, some master protocols, so we can test things in combination, test different arms together, try to get answers as quickly as possible to some of these questions.

You've always been one of the biggest proponents of master protocols. Ca-, can you give, uh, our audience a sense of, of what that means? Because it's really an innovative approach to getting drugs studied and perhaps approved.

Well, master protocol is looking to improve the course of the disease, rather than simply study one agent and get totally definitive information on a single agent. So the master protocol will be focused around the disease, and then can bring in different, uh, agents, test them, perhaps using a common control group, test them against each other, and then sort of pick the winners, and move on to definitive testing for those that look most promising. So it, it has-- it's faster and it has more capacity to test, uh, many products. And it's not over after the end of one clinical trial. It goes on and on, with the hope of improving outcomes of disease over time.

The news media uses a lot of regulatory terms that, uh, people don't often understand, such as expanded access, emergency use. What flexibility, uh, mechanisms are FDA using to try to get answers more quickly about potentially safe and effective treatments?

Well, unlike many diseases, where we use a lot of flexibility, COVID-19 has a very rapid course. It's an acute disease. Right? And so you can use endpoints like mortality, discharged from hospital, whether you need intubated or not, whether you have to go, um, into the ICU, and how much oxygen you're using, and so forth, whether you have to be hospitalized, for example, if you're an outpatient.

And these, uh, endpoints happen very quickly. So we don't need to use surrogate endpoints or many of these other things, because, uh, if we have effective agents, we can get answers really quickly. And actually, we're getting answers if we don't have effective agents quickly, too, unfortunately.

So what we're doing as far as flexibility, we're doing with a lot of trials right now, there are problems with conducting these trials. How do you get informed consent when you can't, uh, contact the patient, where you have-- neither the patient nor the doctor wants to, um, exchange materials, right, that they touch. So we're working with electronic informed consent and other mechanisms.

What about if nobody's allowed in the hospital and the person is unconscious, and so forth. So those are the kind of changes that we are, are looking at. I'd point out most of the drugs that are in, um, testing right now are sort of repurposed.

I was going to ask you about that. They're not new molecular entities. How concerned, though, are you about, um, you know, these uses that aren't on the label that may or may not be part of a drug study?

Well, of course, in the United States and many other places, uh, physicians can write for, and do write prescriptions, for drugs off label, uh, if they so choose to in their professional judgment. However, we're in a situation here where we know nothing. We really don't know what works.

We don't have, you know, some long history with this. We don't have a lot of clinician intuition about what works, because nobody's really seen this virus before. So the-- our goal at FDA is to get studies done as quickly as possible so we can kind of get the sheeps and the goats sorted out here, because there are many, many, many products being used empirically off label, uh, because of desperation. These patients are very sick. And many of them deteriorate.

I mean, there's some reports that as many as 70 different agents are, are being studied. We typically hear about three or four. Does that seem right to you?

Yes. Yes, we have information, and we update it on our web page, the Center for Drugs web page, about how many agents are in the pipeline. And if people have talked to us, how many are in clinical trials, and so forth. And of course, that number will change every day. But we've certainly had more than 70 inquiries about compounds.

The ones that have already been studied in humans or that are approved already, [CLEARS THROAT] excuse me, can go into clinical trials very rapidly. And so we've literally-- we've had dozens of, uh, products go into trials. The ones that are investigational have to go through some type of human safety testing and will get into the clinic slower. But those two will eventually get into the clinic if they're safe enough, and will go into at least screening trials.

Now, you're a rheumatologist by training. And there's been a lot of concern that folks who need some of these drugs, for which is-- are effective treatments for rheumatoid arthritis, aren't able to get them. What is the FDA doing to ensure that there's adequate supply of some of these drugs like hydroxychloroquine, uh, for the treatment of rheumatoid arthritis? And there's a few others as well.

Well, we have, um, really had a huge effort, first on development of new agents to treat this disease, but an equally or maybe even larger effort on the supply chain, which is totally stressed by the consumption, by the demand for critical care products, and then, of course, the anti-malarials to treat COVID-19. And so we work with manufacturers all around the world, find the sources of the drugs, which, of course, we know the ones that are approved in the United States, but even look beyond that. How can the supply be ramped up? Work with manufacturers on how they might change their production to make the supply more available.

Because yes, um, the hydroxychloroquine in the United States is used extensively and particularly for people with lupus. Uh, it's a really necessary drug. And to have-- for them not to have access to it would really, uh, have terrible consequences. So we have done everything we can to try and, um, maintain the drug supply for those patients.

And, and you bring up the drug supply chain, but some folks have argued that many of the sources are foreign sources in areas where COVID-19 is prevalent. So how do you get the workforce, um, to create that supply? Um, do you think it's getting better? Is it getting worse? Uh, what's kind of your counsel in terms of drug shortages? Are we likely to see that in, in a few months?

We're seeing, on top of our usual shortages that we have, which are typically the small volume parenterals for critical care, which, of course--

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--is a complete intersection, unfortunately, with this virus. We're seeing other demand-driven shortages, seeing shortages of fentanyl. We've seen shortages of prof-, propofol, which we've seen on and off, uh, for quite a long time. We're seeing, uh, shortages of sedatives for paralyzing agents, and so forth.

But I think it's a misconception for people to think about, well, um, they, the raw ingredients or perhaps the active drug is made in China, and therefore, going to have a problem. Right now, we have some problems in the United States, uh, of large pharmaceutical plants that are not able to function very well because so many of their workers are either afraid to come to work or they actually are infected. So what we really need, uh, i-, for the drug supply is redundancy around the world.

We need multiple sources of manufacturing. Shouldn't be concentrated just in China, or India, or whatever. And the FDA has been proposing for years that we switch manufacturing to advanced manufacturing, which can be done almost anywhere, and can have that kind of redundancy.

But what we do is we work hard every day. We're tracking these drugs. We're getting additional manufacturers-- say they have, um, an approval to make a drug, but they aren't making it right now-- we're getting them back into the market. Uh, we're trying to manage this, and trying to project, uh, what the demand is going to be over the coming months so people don't run out.

Some people are suggesting that compounding pharmacies be allowed to make drugs in short supply. What's the FDA's position on that? There has been historically problems with some compounding pharmacies.

Well, you have to look at the benefits and the harms. Um, compounded drugs are not going to be of the same reliable quality as, um, drugs that are made under, um, GMP conditions in a, in a, uh, pharmaceutical plant. Uh, however uh, we've recently issued guidance for both your outsourcing facilities, as well as for regular compounding pharmacies that in cir-, circumstances of shortage that they can d-, compound these drugs, uh, during this, uh, crisis.

Well, Dr. Woodcock, I want to thank you for taking time today.

Thank you.

And thank you for watching "Coronavirus in Context" I'm Dr. John Whyte.

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