• Published on Oct 5, 2020

Video Transcript

[MUSIC PLAYING] JOHN WHYTE: Welcome, everyone. You're watching Coronavirus in Context. I'm Dr. John Whyte, chief medical officer at WebMD. Can't turn on the news and not hear about a potential COVID vaccine. But should we really be talking more about potential treatments? Is that one of the most effective strategies to return to some sense of normal? To help provide answers and insights into the role of therapeutics, I've asked Dr. Davey Smith. He is the head of the Division of Infectious Disease and Global Health at UC San Diego. Dr. Smith, thanks for joining me.

DAVEY SMITH: Thanks, John. Thanks for having me.

JOHN WHYTE: I want to start off with the ACTIV trial. And doctors are always good for acronyms. So ACTIV stands for-- I want to get it right. It's the Accelerating COVID-19 Therapeutic Interventions and Vaccines. It's a--

DAVEY SMITH: That is correct.

JOHN WHYTE: --public-private partnership with NIH. What's that all about?

DAVEY SMITH: Yeah, that's a good question. So there's a program at the US government called Operation Warp Speed. And they developed this public-private partnership that they termed ACTIV to develop these coronavirus vaccines and coronavirus treatments, basically as a way to efficiently and very quickly get some good vaccines and therapies out to the public.

JOHN WHYTE: You're a big proponent of therapeutics, that we need to get treatments more accelerated, as well as any potential vaccine. Is that right?

DAVEY SMITH: That is correct. I'm very much a fan. If we could get a vaccine, that would be absolutely great. But we also need therapies. And we know, from our HIV experience, that therapies can really help people live longer, but also be used to control an epidemic. It both decreases the chance for somebody to get sick, but also decreases the chance of somebody spreading it. And those treatments could also be used as prophylaxis. So it really is-- it could really be a very good tool in our tool box to stop the pandemic.

JOHN WHYTE: Do you think HIV/AIDS is a-- is a good comparison? In many ways, that's multi-drug therapy as well. And-- and there's been some preliminary data to suggest that one-drug therapy is not going to be sufficient for COVID.

DAVEY SMITH: I don't really know. I think those therapies-- I think those trials still need to be done. I think in the hospital setting, it is probably going to take more than one drug to-- for treatment for COVID. But in the outpatient setting, one drug might be enough.

JOHN WHYTE: So tell us where we are on treatments. People are talking about remdesivir, dexamethasone, monoclonal antibodies. Where exactly are we?

DAVEY SMITH: So right now, in-- in the hospital-- so when somebody gets severely sick, we have some therapies that seem to have a good signal for working. And that's like remdesivir or dexamethasone. And there's this new drug called [INAUDIBLE] that's coming out, or berry. But we do not have a single treatment for outpatients.

So people, before they get sick-- so they have early COVID. And some of those will progressed to needing the hospital. We just don't have a treatment for those people yet. And that's one of the reasons that ACTIV-2 is testing those drugs.

JOHN WHYTE: What are some of the drugs they're testing? Are they mostly drugs that are already approved and indicated for some other disease? Or are you also thinking about new molecules?

DAVEY SMITH: So right now, we are looking at drugs that were made specifically to target SARS-CoV-2. So this-- the first ones that are going to be used are called monoclonal antibodies. And they are antibodies that have been-- humanized antibodies that are specifically targeted to SARS CoV-2-- and so not repurposed drugs.

JOHN WHYTE: But those drugs are hard to make, are they not? There's challenges in manufacturing. And then we have to sometimes worry about potential side effects given the immune response. Can you give us a-- a quick primer on-- on the role of monoclonal antibodies?

DAVEY SMITH: Sure, so monoclonal antibodies are made from people who got the virus. And then some of those people made really potent antibodies. And we were able to select out those, and then grow those up, and turn those into drugs. And that process is, uh, complicated and, um, can be very expensive to make. But there are about 20-some-odd companies or groups out there have made these monoclonal antibodies specifically targeting SARS CoV-2.

And we've progressed a long way into figuring out how to safely produce those monoclonal antibodies now. So I'm very optimistic that one of those, if not more than one of those, will be ready to use soon for COVID-19.

JOHN WHYTE: I'm going to put you on the spot a little.

DAVEY SMITH: OK.

JOHN WHYTE: What does soon mean? Is that six months? Is it a year? Is it three months? What's your best bet?

DAVEY SMITH: December. So my best bet is, by the end of the year, I think we will have a pretty good new-- monoclonal antibody that will keep people out of the hospital. That is-- that is I'm optimistic. And I-- i-- I-- I do believe that.

JOHN WHYTE: Can we drive manufacturing for monoclonal antibodies to-- to the level that we need?

DAVEY SMITH: That's a good question. We really need to figure out how much capacity each of these companies has to drive manufacturing. Operation Warp Speed has really stepped in to say, OK, if we find a good target, we're going to-- they are going to help drive manufacturing as well, especially for some of these smaller companies that might not have the resources to be able to do so.

JOHN WHYTE: Yeah, you know, I-- I'm looking at some of the information on Operation Warp Speed. And it's interesting that you point out how Operation Warp Speed is also about therapeutics. But all the news seems to be around just vaccine development. Is that a disservice, in any way, to innovation?

DAVEY SMITH: I don't know about it it's a disservice. But I do know that the oxygen in the room is all being taken up by coronavirus vaccines. And I get it. Because we talk about vaccines so much in terms of everybody needs to get their flu vaccines. And there's the anti-vaxxers with measles, et cetera. And we think that having a good vaccine will get us out of the pandemic.

I am less, uh, optimistic on that point. I think we also need treatments. And the reason that I say that is the FDA has said that half-- they will approve a coronavirus vaccine that works 50% of the time. If I get a coronavirus vaccine-- which I will-- if it works 50% of the time, but then I get exposed in the hospital, then I still have a 50% chance of getting sick. And I really need to have a therapy that's going to keep me from getting sicker and perhaps dying, even if we do have a vaccine that works 50% of the time.

JOHN WHYTE: And that might be 50% with two immunizations as well, correct?

DAVEY SMITH: That's right, it might be two immunizations. We also don't know how long that vaccine might last. In regular coronavirus infections, the regular circulating coronavirus infections, we know that immunity wanes pretty quickly. So we don't know what the duration of these vaccines will actually work. But if I had a treatment, I would be a lot-- I would be a lot more optimistic of opening up, uh, businesses, et cetera so that when somebody gets sick, I have something that I can do for them.

I'm an infectious disease doc. And I see lots of people with coronavirus infections and-- get pretty sick. And I want to be able to help them. But at the moment, I-- I have nothing, really, to offer them before they get into the hospital.

JOHN WHYTE: And if people aren't willing to take the vaccine because of concerns that it was rushed or safety, then we still concomitantly have to be developing treatments, correct?

DAVEY SMITH: That-- that is correct. So if-- so you can just-- we talk a lot about, quote, "herd immunity." But you can think of this, that if you have a vaccine that only works half the time, and only half the people take it, you're never going to have enough immunity within a-- in a population to really get rid of that epidemic spread, as we call it, with this virus. So we still need a treatment. Um, and that's what ACTIV-2 is doing. We're really hoping that, uh, we can develop a treatment that then can keep people out of the hospital.

JOHN WHYTE: So therapeutics along with immunization is the real way to return to some sense of normal. Is that right?

DAVEY SMITH: I think we need both. I-- I think that it would be very good if we at least had a treatment so that when people got sick, we could keep them out of the hospital and from dying. And that would really buy us a lot of time to have a good, developed, and safe, effecat-- effective vaccine.

JOHN WHYTE: Why haven't we gotten a vaccine for HIV? Wh-- what's [INAUDIBLE] the commitment we've-- have towards COVID. People have been working 20 years.

DAVEY SMITH: Yeah, a vaccine-- HIV is just such a different virus. It has so much more genetic, uh, mutability. So it just mutates so much better than coronavirus. I-- I do have some skepticism about coronavirus vaccines. I think that maybe the first generation will work a little bit, but not, probably, very well, and maybe have some duration problems, um, which is also what we see with HIV vaccine, um, issues. Um--

JOHN WHYTE: Why do you have that skepticism?

DAVEY SMITH: Uh, because I know that in regular coronavirus infections, our immunity wanes pretty quickly. And the other thing is that people who don't have severe, uh, SARS CoV-2 infection-- so they don't get COVID. They have this asymptomatic-- we don't see them mounting much of an immune response at all. So I'm not sure how a vaccine that basically introduces some viral antigens in there to stimulate an immune response can really, uh, generate, uh, a durable immune response. So that's what I'm worried about.

JOHN WHYTE: Well, Dr. Smith, I want to thank you for taking the time today to-- to help educate us all about what's happening in terms of therapeutics, especially in relation to vaccines. And-- and hopefully, we'll-- we'll have the timeline, uh, that you're suggesting.

DAVEY SMITH: Yeah, I-- I-- I really hope so. And thank you so much for allowing me to come and talk to you.

JOHN WHYTE: And I want to thank everyone for watching Coronavirus in Context. I'm Dr. John Whyte.