Coronavirus in Context: The Promise of Remdesivir for COVID-19 Treatment

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You're watching Coronavirus in Context. I'm Dr. John Whyte, Chief Medical Officer at WebMD. Today, I'm joined by Dr. Stuart Cohen. He is a professor in the Division of Infectious Disease at UC Davis. Dr. Cohen, thanks for joining me.

You're welcome. Thanks for asking me.

There's been a lot of interest in remdesivir. And you're one of the leading authorities with a trial currently undergoing. Can you talk to our audience about remdesivir?

Yeah, so, um, remdesivir is an antiviral drug that blocks the RNA synthesis. Um, so the genetic material of the coronavirus is, um, uh-- is stopped from, uh, being made. And therefore, virus can't be made. Um, in a, um, compassionate use trial of about 56 patients it demonstrated some benefit, um, particularly in people under age 70, um, but even in the sickest of patients.

And so, um, in order to determine whether this drug really is effective or not, you have to do what's called a randomized placebo controlled trial.

OK.

So you can't tell in a-- a single treatment trial whether the patients would have gotten better whether they got the drug or not.

Mm-hmm.

Or they would have gotten worse whether they got the drug or not. But when you have a randomized trial, you have a group of patients that are getting the medications and then a control group. And since we have no specific drugs for coronavirus, the control group has to be a placebo.

And then after you've looked at a big enough group of patients, then you are able to determine whether the group that got remdesivir got better than-- uh, when compared to the group of patients that got a placebo. So--

What about folks that say that's unethical, Dr. Cohen? That--

Yeah, so--

--to be a placebo is-- is problematic.

Yeah, well, so if there was a real treatment, a placebo would be problematic. So for example, if we were doing a clinical trial of hepatitis C, for example, it would be totally unethical to use a placebo. Because you have treatments that work great for these medications. So you need to have a gold standard treatment to compare your new treatment to.

Since there is nothing that's been proven to be beneficial for treatment of COVID-19, um, beyond just, um, supportive care-- so great ICU care, uh, great respiratory management, um, all that other stuff-- the patients get better, um, in a percentage. And the question is whether more get better if they get an antiviral--

Sure. --drug. So--

Now--

So the placebo is just standard care. That's what we would do for anybody without an-- um, an investigational drug available to use.

Right. Because remdesivir is not currently approved for any indication. Is that correct?

That is correct. And-- and this is the kind of study that will end up getting it licensed, um, if it deserves to be licensed based on clinical outcomes.

Now, is this what you're currently doing at UC Davis?

Yeah, so-- so this is a-- a large NIH-funded, um, clinical trial. It's multi-center and actually multinational. Uh, and they just finished enrollment, actually, on Sunday night. And, um, I believe there were over 900 patients enrolled. So there will be plenty of patients and plenty of outcomes. And I suspect that within the next month or so we should have some preliminary data that will allow us to determine whether this drug is, um, uh, going to be the gold standard for treatment and whether it will move forward towards getting licensed. And then anything else that gets studied will have to be studied against remde-- against remdesivir as the, um-- as the comparator if this becomes--

Um, yeah.

--effective.

Are they all hospitalized patients? Is that the patient population--

These are--

--you're looking at?

Yeah, these are-- these are all hospitalized patients. So they can be, um, patients in the ICU or non-ICU patients. But they have to be admitted to the hospital. It's only available as an IV medication.

OK.

So it's not--

And then--

--really an outpatient drug.

What are the outcome measures?

The outcome measures, um, are a little bit confusing, um, to, uh, people. But I'll explain it. So there is a, um, uh, eight numbered scoring system--

Mm-hmm.

--that goes from death at the top to being perfectly fine at the bottom--

Mm-hmm.

--um, and back to your baseline. And what, um, would be defined as a good response is being in one of the three good categories, um, having started in one of the five bad categories. And so, um, it will end up being significantly improved respiratory function--

Mm-hmm.

--or being off oxygen, or going home and being back to nearly baseline. Those are going to be the clinical outcomes that are going to be evaluated. Um, obviously, anything less than that would be considered a failure--

OK.

--um, uh, to treatment. And then they will specifically be looking at mortality rates.

Sure. And you think you'll have data in 30 days?

Uh, I'm hoping that they will.

OK.

I mean, this is-- again, I've mentioned this-- an-- an NIH trial. So I'm not the principal investigator.

Sure.

I'm one of the investigators. Uh, I'm the principal investigator for our site.

Sure. We talked to Janet Woodcock earlier, uh, the director of the Center for Drug Evaluation and Research at the FDA. And she talked about-- there's actually many agents that are currently undergoing trial. We've heard mo-- you know, mostly about remdesivir, hydroxychloroquine, azithromycin, and convalescent plasma.

But you're an infectious disease expert. When we think about these treatments, they all have very different mechanisms of action. Um, so how does that sometimes make sense that we're using drugs for malaria, uh, for this type of respiratory problem? We're talking about convalescent plasma and antibodies. What are we learning about the disease through treatments where we're getting some preliminary data?

Yeah. So I-- I think it may be easier to explain, um, the, um, convalescent plasma. And then I'll get to hydroxychloroquine.

Sure.

So, um-- so when we vaccinate people against viral illnesses, one of the ways that we measure immunity is looking for antibodies, looking for an immune response to the vaccine. When we give convalescent plasma, we call that passive immunity. So the patients, instead of getting a vaccine, they're actually getting the end product--

Right.

--of what a vaccine would provide, with the idea that that will help, um--

Fight the infection.

--people get better and clear the infection.

Mm-hmm.

Because now you've provided a good immune response to the virus. And it helps the body get over it, um, itself. It's the-- it's like it gives it a-- a leg up onto a footstool. Um, the way hydroxychloroquine works is different. The way-- when the virus gets-- attaches to a cell--

Mm-hmm.

--it has to get into the cell. And when it gets into the cell, it gets put in this little bubble. And within that little bubble, hydroxychloroquine changes the acid-base balance so that the virus can't, um, replicate. So it stops it right after it enters from, um, multiplying by changing the pH, changing the acid-base balance, within this little bubble, um, which is, um, called a phagocell.

Sure.

And so I think that is the mechanism.

Mm-hmm.

And so-- and-- and suffice it to say, just using HIV as an example, we have things that target the enzymes that replicate HIV.

Mm-hmm.

We have, um, uh, drugs that target what's called the protease, which actually splits--

Yup.

--the HIV proteins up and allows it to be made into a whole--

Mm-hmm.

--virus. We have targets against what's called the integrase--

Mm-hmm.

--which is what makes the HIV s-- stick into cells and never--

Right.

--come out again. And so they're all different targets--

Mm-hmm.

--that people go at when they develop antiviral drugs. Um, one size doesn't always fit all. And for each, um, virus, um, a different drug--

Mm-hmm.

STUART COHEN: --and a different target may be a preferred one.

Sure. On HIV, it took us many years to get to this point of triple, quadruple therapy from the early days of ACT. Let's kind of move over to the vaccine issue, where some folks are suggesting this is a 12 to 18 month endeavor. We're still searching for a vaccine for HIV. It's taken more than a decade to really fine tune a vaccine for shingles. What's kind of your thoughts or where-- on where we are in vaccine development for coronavirus?

Yeah, well, that's, um, a very interesting question. Um, and I will just start out by saying not every virus is the same. And, um, maybe one way I can sort of, uh, describe this is to say that, um, part of the way that viruses survive is to make mistakes when it multiples so that there's a lot of different viruses that are all very related, but they're just a little bit different.

Um, this is called mutations. And these mutation rates for something like HIV are pretty high. And so part of the reason that people haven't been able to develop a vaccine to HIV is because the target keeps moving.

Mm-hmm. And the virus has the capability of moving past that target. So you have a vaccine that targets one thing. And all of a sudden, it slips over to the right by making a few changes. And it avoids your vaccine.

The coronavirus is new enough now that I don't think that we totally know what the mutation rate is. So how fast it changes. And that may determine how elusive a vaccine is. So if it doesn't mutate rapidly, then I think there's a better chance to develop a vaccine than if it does mutate rapidly.

The other thing is that HIV is a-- a chronic infection.

Sure.

Um, shingles is a chronic infection.

Mm-hmm.

Right, they-- once you get them, you never get rid of it. Um, the vaccine just keeps everything in check. Um, for, um, coronavirus, this is presumably an acute infection.

Mm-hmm.

And people get over it. And eventually, they clear the virus. So it's a little bit more analogous to influenza.

OK.

I'm not sure that we've been that successful with--

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I was going to bring that up. We have-- [INTERPOSING VOICES]

I get that part too. Right.

So let's-- so now I get to ask you, what's your best bet--

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--in terms of timing for coronavirus. You opened the door. So--

Yeah, I know. I-- I-- I stepped right into it, didn't I?

What's your best bet?

I, uh-- that was a-- uh, a faux pas.

Mm-hmm.

So I think, um, what I would say is that, um, you know, 12 months I think is a-- is a-- definitely a short line.

Mm-hmm.

Um, uh, I-- I would be surprised if it was something that fast. Um, I think even though vaccine technology has moved on rapidly, I think you still have to prove that it's safe. You still have to prove that it actually does--

Correct.

--something. And so I think, um, 18 months is probably realistic. Um, and then I think we're going to have to see over the next month or two as people start doing gene sequences of sequential--

Mm-hmm.

--coronavirus, um, uh, samples, whether it changes a lot. And if it does, then I think it's going to be a lot more difficult--

That's right.

--story. And 18 months may be optimistic.

Right. Where do you think we'll be on treatments in six months from now?

Yeah, well, I'm-- I'm hopeful that we will have treatment in six months. I'm hopeful we'll have good news in a month and that we will have something to start working on. And then other-- other drugs that follow it along. There are a lot of, lot of drugs being developed.

Yes.

We've been, um, approached for multiple, multiple clinical trials. And there are a bunch of different ways in which people are going at it. So I'm much more optimistic about drug treatment than I am about vaccines.

That's good. Well, maybe we can check in with you in another month and-- and see how things are going.

Uh, that would be great.

Thanks for joining us today, Dr. Cohen.

Thank you.

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

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