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Hello. I'm Paul Auwaerter with Medscape Infectious Diseases and the Johns Hopkins University School of Medicine. Some of the most frequent questions I fielded recently, besides vaccine-related COVID questions, have to do with the use of the two monoclonal antibody products that now have US Food and Drug Administration (FDA) emergency use authorization (EUA).
Convalescent plasma was first on the scene in August and has an EUA for hospitalized patients who may have oxygen requirements or otherwise. I think this has caused some confusion, because both of the monoclonal antibody products I'll be discussing have had studies that have not shown benefit or have been associated with worse outcomes for hospitalized patients, especially those on high-flow oxygen or in the intensive care unit (ICU).
First and foremost, the two monoclonal antibody products are both used for outpatients who have confirmed COVID-19 with SARS-CoV-2–positive testing.
The first EUA granted was for bamlanivimab, which is a single monoclonal antibody — an IgG — directed against the spike protein that has neutralizing properties.
The data that the FDA used were from the BLAZE-1 trial, which looked at a single dose in a dose-finding trial of three different dosages for 452nonhospitalized patients. The primary endpoint was change in viral load, which was not met, but there was a suggestion that a secondary endpoint was beneficial, which was the need for hospitalization or an emergency department visit at day 28: 1.6% in those who got the monoclonal antibody vs 6.3% who got the placebo.
It's unclear exactly how many of these were in the emergency department, avoided visits, or were in the hospitalization group. This difference was not deemed to be significant enough by the Infectious Diseases Society of America, and the National Institutes of Health (NIH) deemed this as insufficient data to make a recommendation. But there is biological plausibility for giving antibody-based therapy early in the illness as an antiviral to halt progression of infection. For that reason, I think it's a reasonable choice to think about. This is approved for high-risk patients.
Casirivimab and Imdevimab
The second product to receive approval is a combination cocktail of casirivimab and imdevimab, formerly called REGN-COV2, which is the Regeneron product. Although bamlanivimab has already made it to a number of centers (I saw patients receive their first infusions last week, here in the Baltimore area), the monoclonal antibody cocktail, although approved recently, hasn't yet been distributed.
The little bit of data that I'm aware of is from a press release in late October of nearly 800 outpatients. The endpoint was reduced medical visits through day 29. The determination was that this cocktail led to a 57% reduction (2.8% vs 6.5%), which was statistically significant. Those who had one or more risk factors actually had a 72% reduction. Most of the benefit was seen in patients who had not yet mounted antibody responses (ie, their blood did not contain their own antibodies), suggesting that early administration may have benefits. There are few adverse events with this monoclonal antibody cocktail, but we've not seen any more in-depth information yet.
The FDA did grant its approval, and it, too, has an EUA that is very similar. It is approved only for patients who have documented COVID-19, who are outpatients, and who are at high risk for complications or hospitalization. These include anyone with a body mass index (BMI) over 35 kg/m2; anyone with comorbidities, such as chronic renal disease, diabetes, or immunosuppressive illness; those taking immunosuppressive medications; or those over 65 years of age. Also included are patients over 55 with cardiovascular disease, hypertension, or pulmonary disease. There are also some criteria for adolescents — since it's approved for anyone age 12 or older — who have certain risk factors that are outlined in the EUA.
Nothing Is a Home Run
Either of these is possible. They both probably work the same. They should be given as soon as possible. This speaks to a separate issue with testing bottlenecks, with so many people seeking testing. There are delays in getting a test, and it could be argued that antigen testing might have an even bigger role to try to find people who are in their early phases of illness and highly infectious, and who could benefit from such therapies.
Again, there aren't large amounts of data yet, given the trial sizes, and probably the number needed to treat to really have some impact on a larger scale or on mortality would be very difficult to achieve. Interestingly, the Eli Lilly product — the single antibody — won't be made any further, and they, too, are investigating a cocktail.
This kind of strategy for early treatment is going to be a minor contribution from a prevention standpoint before we have widespread, effective vaccines. Studies remain in progress where it might have a larger role (although a very expensive one) in preventing disease in patients who might be at [higher] risk — especially, for example, in congregate living facilities or nursing facilities. Unfortunately, we will need to wait for data to see if this is effective.
So, we have some newer therapies. Nothing is a home run, but these are things you might consider for your very high-risk patients if they can get in early to actually get these intravenous infusions, which have some considerable logistics of trying to get people in early, getting the intravenous infusions over an hour, and personnel concerns.
Thanks very much for listening.
Paul G. Auwaerter, MD, is a professor of medicine at the Johns Hopkins University School of Medicine and clinical director of the Division of Infectious Diseases. His areas of clinical expertise include Lyme disease, Epstein-Barr virus, and fever of unknown origin. He has been a Medscape contributor since 2008.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Paul G. Auwaerter. Monoclonals for COVID-19 a 'Minor Contribution' - Medscape - Dec 07, 2020.