COVID-19 Treatments: FDA's Woodcock on Current Drug Trials

John Whyte, MD, MPH; Janet Woodcock, MD

Disclosures

April 23, 2020

Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

This transcript has been edited for clarity.

John Whyte, MD, MPH: You're watching Coronavirus in Context. I'm Dr John Whyte, chief medical officer at WebMD. I'm joined today by Dr Janet Woodcock, director of the Center for Drug Evaluation and Research at the US Food and Drug Administration. Dr Woodcock, thanks for joining me.

Janet Woodcock, MD: It's great being here.

Whyte: To start off, do we know if there are any safe and effective drugs for COVID-19?

Woodcock: No, not yet. There are certainly a lot of people working on it, but nothing has been shown yet to be effective.

Whyte: Are we undergoing clinical trials for drugs like hydroxychloroquine, remdesivir, convalescent plasma? Can you give us a sense of where we might be?

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

We'll be reading out over the next 5 months or so in everything from preexposure prophylaxis to very ill patients. In the meantime, there are a lot of immunomodulators being tested for the later stages of the disease. And those should have readouts starting perhaps at the end of next month and into the summer, for the various agents.

Whyte: In your mind, when we think about these different treatments—some are antivirals, some are anti-infectives, some are relating to cytokine storm—do they tell us about the pathophysiology of the disease? Do we know the mechanism of COVID-19? What are your thoughts on that?

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

There are still questions about how much of this is overwhelming virus infection and how much of it is due to an overexuberant immune response toward the end of the disease.

Whyte: And even if we're treating it as an ARDS, it could be more high altitude as well. There's been a lot of discussion about ventilator protocols.

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

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

Woodcock: 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. The master protocol will be focused around the disease and then can bring in different agents and test them—perhaps using a common control group—against each other, and then sort of pick the winners and move on to definitive testing for those that look most promising. It's faster and it has more capacity to test 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.

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

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

And these endpoints happen very quickly. So we don't need to use surrogate endpoints or many of these other things, because 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.

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 contact the patient, when neither the patient nor the doctor wants to exchange materials that they touch? So we're working with electronic informed consent and other mechanisms.

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

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

Woodcock: Of course, in the United States and many other places, physicians can and do write prescriptions for drugs off-label 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 some long history with this. We don't have a lot of clinician intuition about what works, because nobody has really seen this virus before. So our goal at the FDA is to get studies done as quickly as possible so we can kind of get the sheep and the goats sorted out here, because there are many, many, many products being used empirically off-label because of desperation. These patients are very sick. And many of them deteriorate.

Whyte: There are some reports that as many as 70 different agents are being studied. We typically hear about three or four. Does that seem right to you?

Woodcock: Yes. We have information, and we update it on our web page about how many agents are in the pipeline, 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 can go into clinical trials very rapidly. We've had dozens of 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.

Whyte: You're a rheumatologist by training, and there has been a lot of concern that folks who need some of these drugs, which 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 for the treatment of rheumatoid arthritis? There are a few others as well.

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

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

Whyte: You bring up the drug supply chain. 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 to create that supply? Do you think it's getting better? Is it getting worse? What's your counsel in terms of drug shortages? Are we likely to see that in a few months?

Woodcock: We're seeing, on top of our usual shortages that we have, which are typically the small-volume parenterals for critical care—which is a complete intersection, unfortunately, with this virus—other demand-driven shortages. We're seeing shortages of fentanyl. We've seen shortages of propofol, which we've seen on and off for quite a long time. We're seeing shortages of sedatives for paralyzing agents and so forth.

But I think it's a misconception for people to think that because the raw ingredients or perhaps the active drug is made in China, we are therefore going to have a problem. Right now, we have some problems in the United States with large pharmaceutical plants being unable to function very well because so many of their workers are either afraid to come to work or they are actually infected. So what we really need for the drug supply is redundancy around the world.

We need multiple sources of manufacturing. It 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.

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

Whyte: Some people are suggesting that compounding pharmacies be allowed to make drugs in short supply. What's the FDA's position on that? Historically, there have been problems with some compounding pharmacies.

Woodcock: Well, you have to look at the benefits and the harms. Compounded drugs are not going to be of the same reliable quality as drugs that are made under good manufacturing conditions in a pharmaceutical plant. However, we've recently issued guidance for both outsourcing facilities as well as regular compounding pharmacies that, in circumstances of shortage, they can compound these drugs during this crisis.

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

Woodcock: Thank you.

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

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