Coronavirus in Context: Updates on COVID-19 Clinical Trials

[MUSIC PLAYING]

Welcome to Coronavirus in Context. I'm Dr. John Whyte, Chief Medical Officer at WebMD. My guest today is Dr. Paul Kirchgraber. He's the CEO of Covance, LabCorp's drug development program. Dr. Kirchgraber, thanks for joining me.

Thanks for having me on John. I appreciate it.

Let's get right to it. Where are we in potential treatments for COVID-19?

That's a great question, John. I mean, as one of the leaders in the pharmaceutical research and development and helping our clients get new drugs to the market, we see a broad swath of the market. Right now, there are over 800 clinical trials currently registered on clinicaltrials.gov involving COVID and some sort of former others. So some of those are on the early development side, some of those are later testing in human side, and some of those haven't started yet. But anyway, over 800 total trials that we've seen.

Where are we, and, you know, probably the second part of that question is when are we going to get a cure or when are we going to get some other treatment for it? I don't know the exact answer to that, but what I can tell you is, right now we're seeing more collaboration in this industry than we've ever seen before. We're seeing regulatory groups like the FDA be much more approachable, if you will, in terms of getting approvals for an IND, which is the first part of getting a new drug for testing in humans. We're seeing collaboration between academic centers and pharmaceutical companies more than usual. We're seeing pharma and pharma companies that were competitors, that were used to compete, collaborating now in this area more than usual.

But to your question, you know, it depends on where the drugs are in the development cycle. Look at chloroquine and hydroxychloroquine, which I think originally people thought those are approved drugs, they're on the market, manufactured already, let's try them. And, you know, there's been lots of controversy about those drugs, certainly some early hopes on those drugs, but what we've seen let's say going from a plus minus type situation, maybe they work, maybe they don't, to recently there was a VA study that was just released that said, using chloroquine in patients didn't reduce the time that they had on a ventilator. And in fact, the death rate went up in most patients.

Not a controlled trial, and-- and pre-drug, so we still have to look at it. But Paul, in your mind, are we going to have more success-- you referenced an IAND for an investigational new drug. And we were talking to Janet Woodcock recently at-- at FDA. Is the greatest bang for our buck in COVID-19, is it along the lines of new molecular entities, or is it more along the lines of drugs that are currently approved and we try it for another indication, kind of like hydroxychloroquine? But as you noted there-- there are other drugs.

Yeah.

Where do you think our efforts are best put?

So right now I would say there are efforts across all the different areas, so approved drugs, as well as novel drugs being developed. If you're looking at timelines, fastest, if-- if you will, or the best ability to get a-- a drug quickly, it's in those drugs that are either already approved or already worked on for other indications.

There's one drug out there right now that's shown a lot of promise. It's been in the press called Remdesivir. That was developed for Ebola, actually. So it's been through a lot of the preclinical portions of the drug development process. And there's lots of ongoing trials now with Remdesivir. In fact, there was a leak recently in the popular press out of Chicago where some early-- but again, uncontrolled-- results from one study that showed some promise with that drug.

So that's a good example of a drug that was fairly far along in the developing process that showed some promise. But again, the trial's not closed yet. We don't have all the data on that, so I would withhold full judgment on that. So those--

[INTERPOSING VOICES]

And it was not-- it was actually not approved for anything. So it's actually--

Correct.

--out there, but actually has no approved indication. What about something like convalescent plasma?

Yeah. That's an interesting one. And that's been used for years, as you know, um, decades, certainly, and taking-- and the thought there is you take plasma from somebody who's recovered from the disease. You withdraw the plasma. You take out the antibodies, if you will, and then you give the antibodies to somebody else.

There's been multiple studies on that, John. You're probably aware. A lot of them have been really small numbers, so the numbers of patients, you know, 10 or something like that.

Labor intensive. People don't realize.

Very, very labor intensive. And difficult to bring to full-- like, a production scale where you could treat the entire US population. So right now, convalescent plasma is used in very extreme cases where first you can identify a patient who has sufficient antibodies. And second, you have a very sick patient and you're-- you're trying to recover them in any way possible. So I don't see that as a long-term solution to this problem.

And how is COVID-19 changing how we do clinical trials-- not just for coronavirus, but for other trials, as well? You referenced, you know, some of the FDA's flexibility. It's hard to get in-- to get patients to enroll in trials if they can't actually come to the site. Clinical trial protocols often require lots of collection of specimens. Maybe they're all not as needed. What are your thoughts about how COVID-19 is changing the clinical trial development process?

Yeah, that's a great question, John. Because for a long time in the pharmaceutical world with regulatory agencies as well as academic centers and pharma companies that are involved in the process, we've been talking about trying to get to a point where we can have what's called a decentralized trial or a virtual trial. And lots of discussion around it. What's the right indication? And when would we do it? When would the regulatory agents approve such a thing?

Now with COVID, as you mentioned, doctor's offices are closed. Hospitals are treating the sickest COVID patients. So if you're on a current protocol, maybe for breast cancer or lung cancer or some-- a very important treatment, you can't get to your normal physician, just like no one else can get to their physician unless they have a pretty sick disease right now.

So if you want to continue your therapy, your novel therapy for breast cancer, we have to do that in a hybrid or virtual trial, so like we're doing today. Instead of going in to see your doctor, you're going to do a video conference like we're doing today. We have what's called monitoring activities that occur throughout the trial to make sure that the physicians and the folks that are running the trial are doing it to FDA standards.

Normally those are on-site visits. Now we're doing remote visits. So what we're seeing here in my opinion is a tipping point in the industry so that you're seeing much wider acceptance of video conferences, of remote visits, of patients seeing their doctor via teleconference and not having to go into the doctor's office on a regular basis, so just like regular clinical medicine, in clinical trials we're seeing a lot of movement towards decentralized trials or virtual trials.

Do you think you'll see more trials being conducted in the home where you're actually sending personnel to the patient as opposed to the patient coming to you, finding a place to park, dealing--

Absolutely.

--with traffic?

Absolutely.

And that's-- you know, when you talk about a decentralized or a virtual trial, I like to say there's two parts to it. There's the arms and legs piece and there's a technology piece. So the technology piece is what we're using now, and-- and what you can use videoconferencing and other things like it. But the arms and legs piece, a lot of times, is a visiting nurse type service where you have someone actually go out to the patient's house and draw blood or give them the dose of the drug that they normally would have gotten at the physician's office.

So they can bring the dose with them. They can also talk to the patient and say, how's it going for you? Are you having any side effects? Have you noticed anything different? And gather that kind of social history and the history piece of the physical exam that you can't do remotely.

Put on-- or take out your crystal ball, rather. Tell us where we are in six months in drug trials for coronavirus.

Yeah. So none of us really have a crystal ball. But where are we-- I-- I think we'll see more advancement of some of the antiviral drugs that we talked about before, because some of them were already in process, and even the novel ones are advancing pretty quickly. So those are in the clinics now, first in human type testing. Those could get into phase 2 and phase 3 trials, meaning broad global randomized clinical trials within that time frame.

Uh, vaccines and vaccine development is progressing at a very rapid pace. There has been a couple of manu--

Do you think it's 12-- do you think it's 12 to 18 months, as some people have said? What's your best-- best bet?

So there's a couple of pieces to that. I would say for a full vaccine that's widely available to the entire population of the United States, we probably are looking at somewhere in that 12 month time frame. There's been two manufacturers that have come out and said that they think they will have a vaccine available by the end of this year. They've said late fall, early winter, for health care workers only. And that's mainly because of the supply chain issues. They just don't feel they'll be able to produce enough vaccine [INAUDIBLE].

Do you think that's realistic based on where we are today?

Well, there's some folks that have decided to actually produce vaccine ahead of their clinical trial being finished. And there's two of the vaccines that are currently being worked on that are novel vaccines in that instead of the usual way of taking an attenuated virus or a virus that's-- can't do any harm to you and injecting that as part of the vaccine, they're actually using messenger RNA. And messenger RNA injected into the muscle is going to produce antigens, the antigens on the surface of the virus that generate antibody and give you the immunity.

So they're going to use your, uh, body's system, if you will, to produce those antigens. And then you develop antibodies and you get immune to the-- to the virus. That's the theory. Those are actually much faster to produce than a traditional vaccine. Now, there's never been one approved in the United States that I know of, a messenger RNA vaccine.

But there's two. There's one on the west coast being developed by one company. And there's one that was just announced that's starting in Germany with the same general concept. So those two show promise as long as they have efficacy or they hit the target, they work the way that they should, to actually be produced in mass quantities faster than a traditional vaccine.

What do you think about the role of cytokine storm? Have you been following that in terms of potential drug development?

Yeah, absolutely. And-- and that, most people think that for the sickest patients-- and the majority of people who get COVID do not get this sick. About 5%, um, experience very, uh, significant pulmonary symptoms and end-- end up intubated. For that population-- and it happens about 10 days out in the course of the, uh, disease that that population is-- it's a cytokine storm that's causing that.

So there's several medications that are already approved in areas of rheumatoid arthritis and lupus that manage some of the cytokines like interleukin 6, anti-interleukin 6 drugs, which are being used, um, in the fight to try and manage that cytokine storm. Again, randomized clinical trials are under-- being undertaken right now. Um, and we don't have the results of those trials yet.

So you think we'll see improvements in the way that we do clinical trials post COVID-19? Absolutely, yeah. We will definitely see more virtual or decentralized trials. I think you'll see the regulatory agencies open up to that concept, uh, pharmaceutical companies are certainly open to that concept right now. Um, and I think patients have come to expect it. You know, most people get used to video, things on their iPhone, um, immediate results. That's common in our society outside of the medical care world. And I think we'll just-- there's a lot of pressure for it. We'll see a-- a big change there.

Well, I want to thank you for sharing your insights with us this morning.

Thanks, John. It was great to be on your show. Appreciate it.

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