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The US Food and Drug Administration (FDA) granted emergency use authorization (EUA) for monoclonal antibodies (copies of human antibodies that can introduce an artificial response) for people who are at risk for hospitalization due to COVID-19.
The FDA granted the EUA on the basis of three studies that showed that use of monoclonal antibodies decreased viral load, symptoms, and hospitalization. The therapy is given early in the disease course via IV infusion in an outpatient setting.
Operation Warp Speed is working on making monoclonal antibody treatment more widely available, publicizing where people can access treatment and allowing nonhospital healthcare settings to order the therapy directly.
High-risk patients with mild COVID-19 symptoms should "aggressively" pursue monoclonal antibody treatment at a doctor's office or a clinic. Once hospitalized, it's too late to receive monoclonal antibody treatment.
Ongoing studies are examining whether "pre-exposure prophylaxis" — giving monoclonal antibodies to someone who has been exposed to COVID-19 but is not infected — is beneficial.
This transcript has been edited for clarity.
John Whyte, MD, MPH: Welcome, everyone. I'm Dr John Whyte, chief medical officer at WebMD. You're watching Coronavirus in Context. Everyone is talking about the vaccines, and it's good that we're having those discussions. But we can't forget about therapeutics.
One of the topics I want to talk about today is monoclonal and polyclonal antibodies. I've asked Dr Janet Woodcock to come back and explain to us about monoclonal antibodies — when they should be used, how we should be using them. She is the therapeutics lead at Operation Warp Speed. Dr Woodcock, thanks for joining me.
Janet Woodcock, MD: Great to be here.
Whyte: Now, full disclosure: I mentioned once before that Dr Woodcock is my former boss. But I'm still going to be tough on her with questions. Let's start off, Dr Woodcock, and remind our audience what monoclonal and polyclonal antibodies are.
Woodcock: Monoclonal antibodies are artificial antibodies that are made in factories or in a laboratory. They're modeled on (often exact copies of) an antibody that a human made in response, in this case, to getting infected with the coronavirus. So they're a way of introducing this immune response artificially. It's called "passive immunity."
Similarly, some polyclonal antibodies are from convalescent plasma that's been taken from people who are recovering and have the antibodies in their blood. They can be taken out and given to somebody who's sick to boost their antibody response. So, all of these are types of what's called passive immunity.
Whyte: People have heard about monoclonal antibodies (some refer to it as a cocktail) because the president has received it, among other therapies. Some other key politicians and celebrities have also received it.
I want to talk about what the US Food and Drug Administration (FDA) authorized in terms of monoclonal antibodies. It is for persons with moderate to severe disease with at least one comorbidity, who are not currently hospitalized but who are at risk for hospitalization. Is that correct, Dr Woodcock, in terms of the emergency use authorization (EUA)?
Woodcock: Well, you can have symptomatic disease of any kind. It's really important that we get it to high-risk people. That's most important. The EUAs are for people who are at high risk of getting hospitalized. That's anybody 65 and over, or people 55 and over who have certain comorbidities, or even younger people with certain chronic diseases.
All of those people are at high risk to get hospitalized. We believe that giving them antibodies will help keep them out of the hospital. Most people, on the other hand, will recover on their own and therefore aren't at high risk of having a severe disease.
Whyte: There have been a couple of studies published in peer-reviewed journals that people have interpreted in different ways in terms of the strength of the evidence. There are some data purists who feel that we always need more data. Then there are others who are saying, "We're in the middle of a pandemic; we need to show flexibility in terms of making treatments available." How should we interpret some of the studies that have come out about the use of monoclonal antibodies in the treatment of COVID-19?
Woodcock: Most studies were by virtue of just the timeframe. The "virologic endpoints" in those studies look at whether monoclonal antibodies reduce the virus in people. But they also looked at what we call "clinical endpoints" — hospitalization symptoms and so forth. Those weren't the main points of the studies. So that's the issue. They looked at different doses; both the Regeneron antibody and the Eli Lilly antibody looked at different doses in their trials and looked at virologic endpoints.
It showed in both cases that giving people the antibodies decreases the [viral load]. It knocks down the virus faster. It also showed that symptoms were decreased; it shortened the [period] of symptoms. But there weren't enough hospitalizations to get that statistically significant result that people are looking at. In all three of the studies that have been completed, there was a big reduction numerically in hospitalizations in each one of those studies — two of them by Lilly, one by Regeneron.
That was the basis upon which the FDA granted the EUA, thinking that we have nothing else for our patients. We have no treatment to keep them from getting in the hospital. And here we've had, repetitively, results that show that you can knock down the virus with the intervention. Numerically, you have significantly fewer hospitalizations. That's the reason for this authorization and the reason for using monoclonal antibodies. There will be more studies coming along and there will be more data. But that's what we have right now.
Whyte: What do you say to people who are arguing that we need to have more data? The Infectious Diseases Society of America has been very lukewarm about the use of [monoclonal antibodies]. You and I have had those discussions in the past. There comes a point in time when you have to base the decision on available information that you currently have. You've been in drug development for 30-plus years; how do you weigh this when it comes to the use of these therapies?
Woodcock: Like any other treatment. We usually have much less evidence on cancer treatments for people who have metastatic disease vs evidence on a new headache treatment or even an antidepressant. It really depends on the circumstances.
Here I would take a "weight of the evidence" approach. Sure, we don't have a primary endpoint of hospitalization in any of these trials. What we have, though, is the decrease in the viral load, the decrease in symptoms, and then the numerical decrease in hospitalizations. Given the fact that the hospitals are overloaded and we can't take care of all of these people, it would seem prudent to deploy therapies that can keep people out of the hospital if there's a very high probability that they can do that.
Whyte: Part of the challenge — correct me if I'm wrong — is that we want to give these therapies early on. That's often where they have the greatest effect. But people need to come in to a clinic, an infusion center, to get this therapy. We've been telling patients for so long "Don't come in," or their primary care physicians aren't that familiar with this therapy. And that's where patients with the early symptoms that meet the criteria that you just discussed are going early on.
So, what do primary care physicians and others need to know about this therapy? Waiting too long, until patients are hospitalized, is going to be less effective, and the hospitals are overwhelmed to think about giving this therapy. What can we tell primary care physicians and others who are on the front lines seeing patients or talking to patients through telemedicine and telling them they need to come in to potentially receive this therapy?
Woodcock: First of all, as far as we can tell right now, the therapies are not indicated for inpatients. So, you're right; it has to be early in the course of disease, and people have to have awareness.
We are going to try to do a better job at Operation Warp Speed of making these more widely available so that primary care knows how to get ahold of them. But still, there has to be an ability to give an infusion to an infectious person for an hour and then observe them for an additional hour and do all the procedures around that.
Whyte: Do you think people are thinking it's more complicated than it really is when they hear "infusion"? We do infusions all the time in clinics.
Woodcock: I think the infusion itself is very simple. It can be a gravity-based infusion; you don't need a pump. You simply need the ability, if someone has an infusion reaction, to respond. But you don't have to be in a hospital setting or a hospital clinic adjacent to a hospital. We're seeing it done in nursing homes now where there are outbreaks. And that's happening very successfully. So, it isn't that challenging except for the fact that these people are infectious, so they can't be mingled with the usual infusion clinics where you have cancer patients and immunocompromised people coming in.
Whyte: The distribution of monoclonal antibodies is somewhat unusual, in the sense that the government has purchased them directly. With the way they've been distributed, sometimes it can be confusing for either patients or physicians to figure out if their nearest institution offers this therapy. How do we address that?
Woodcock: We're trying to take steps to address it. We would like to publicize where these monoclonals are available. We'd also like to open up to direct ordering so that nonhospital groups that would like to order it and infuse the monoclonals would be able to do that. I think there are many settings where these actually can be given to outpatients. The original distribution was based on how remdesivir was distributed; that was given to hospitals. But, of course, remdesivir was an inpatient drug.
Whyte: Right. That's inpatient, but this is an outpatient drug.
Woodcock: That's right. We're going to have to broaden the circle because it's clear that even in a hospital emergency department, even in a large hospital system, there is only so much throughput they can do with infusions. The biggest challenge right now is logistics, getting enough nurses and other personnel, because they're all taking care of COVID inpatients. It's sort of a chicken-and-egg problem, because if we could only treat the outpatients, we could have fewer inpatients. But we're so consumed with dealing with inpatients that it's hard to treat the outpatients. It's a new thing; people are hesitant and the evidence isn't the traditional evidence.
Whyte: We're not having that mindset whereby if patients are coming in to the clinic with their symptoms, or they're doing a telemedicine visit, they may actually be eligible for this therapy. When do you think the distribution will be improved in terms of direct distribution to clinics? Or some other strategies, like patients being able to look online and see whether a clinic around the corner offers this therapy?
Woodcock: We're targeting early January for some of those improvements and hopefully will keep it going and broaden them. Despite what people think right now, there is not a shortage of the drugs.
Whyte: I was going to ask about that. So let's be clear. Early on we heard that these are very expensive to make, it takes a long time...
Woodcock: That isn't totally competitive with what private insurance would give, but it could be in the ballpark. Health systems may have incentives to treat people to keep them out of the hospital because the cost they're bearing of hospitalization — not the financial cost necessarily, but the cost to their personnel and so forth — is so devastating.
Whyte: I started off with the mention that everyone's talking about the vaccine. But we need to remember these therapeutics, including monoclonal and polyclonal antibodies. For consumers who are listening, what should they take away from this, either for themselves if they're having symptoms of COVID or for a loved one or someone else? We don't want them to wait too long, until someone has to be hospitalized, to think about this. As you know, sometimes the squeaky wheel gets the grease. Do they need to be talking to their doctor and doing a little bit of their own homework to try to find out where they can get these?
Woodcock: What we've seen is that people who know about this and who are determined can get it. They will be able to locate a place where they can get an infusion. As I said, many patients out there are not that interested. They don't feel well; they don't want to come in and get stuck with an IV, and do this and that. Right? They're sick. But those may be the people who need it the most.
People who are at high risk, who are 65 and older, and especially if they have other chronic medical problems, really should aggressively consider getting outpatient treatment before they get too sick. Because if you're in the hospital, it's too late to get a monoclonal antibody and you need other kinds of treatment. They should call their health provider and be aggressive, and research around, because these drugs are being offered at many outlets around the country.
Whyte: And for our clinical colleagues, what about the concept of pre-exposure prophylaxis? You mentioned nursing home outbreaks. Currently, this is for patients who actually do have COVID. Is there a role for these monoclonal antibodies in people who potentially have had exposure but don't necessarily have COVID? What are the latest data there?
Woodcock: The data are not available yet but should be arriving soon. There are ongoing studies looking at pre-exposure prophylaxis particularly in nursing home residents, because that's one of the populations that's really contributing to the mortality rate for this disease.
Within the next month, we should be hearing some information about the use of monoclonal antibodies for a pre- or post-exposure prophylaxis before people are actually infected. But it's very clear that once they're infected, if they're in that high-risk category, they should be treated if at all possible.
Whyte: Finally, what do we say to clinicians who are overwhelmed right now? What advice and guidance can you give them to think about this therapy in their decision-making?
Woodcock: My advice and guidance would be, to the extent possible, for people to band together and think about centralizing in groups or in communities an infusion program, so that each group isn't flailing around all the time trying to find a treatment for their patients. For example, here in Maryland, there is a field hospital at the Baltimore Convention Center. People can simply refer those who are positive and high-risk, and they can get their infusions there.
I think centralizing or finding somewhere where these infusions can be given — there has to be a little bit of proactivity. I know that's tough when people are tired, overwhelmed, and have so many other demands. That's really part of the problem. For the next several months as we continue to have high-risk people become infected, needing hospitalization, and having to go into the ICU, trying to treat them early and keep as many as possible off of that path would help us all.
Whyte: We've talked about the benefits. What are the risks?
Woodcock: There are infusion reactions; they are not super common. I think people are very familiar with monoclonal antibodies because they're used so much to treat autoimmune diseases, GI diseases, cancer, and so forth. Those are usually pretty well managed. They can be somewhat serious. But the conditions of use require that you have the kind of medications — Benadryl, epinephrine, and so forth — nearby and that you have the ability to call emergency services if someone really got ill. But in general, we're hearing from the community that is administering these that they're well tolerated.
Whyte: Well, Dr Woodcock, I want to thank you for all that you're doing to keep us safe, for your role with Operation Warp Speed as well as at FDA. We'll continue to check in with you to learn the latest of what we need to be doing as patients, clinicians, and caregivers. Thank you for taking the time today.
Woodcock: Thank you very much for getting this information out. I think it's really critical, and I appreciate it.
Whyte: If you have a question about monoclonal antibodies, a COVID vaccine, or anything else related to COVID, send it my way. You can email me at email@example.com or post it on one of WebMD's social media. Thanks for watching. Remember, stay positive and test negative.
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Cite this: Should You Prescribe Monoclonal Antibodies for COVID Patients? - Medscape - Jan 05, 2021.