A: Currently, the evidence is not yet clear, and we need lots more data.
The FDA issued an Emergency Use Authorization (EUA) for bamlanivimab use in non-hospitalized patients with mild to moderate COVID-19 on November 9th. Bamlanivimab is a neutralizing monoclonal antibody that targets the spike protein on the SARS-CoV-2 virus. The goal of neutralizing monoclonal antibody medications is to stop the virus from entering cells and making a bunch of copies of itself, hopefully keeping that person from getting much sicker.
The EUA was issued based on 2 studies: the BLAZE-1 study and the ACTIV-3 study (yes, I do think people spend a lot of time coming up with catchy names for studies).
The Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) trial is a randomized, double-blinded, placebo-controlled trial that was looking at the safety and efficacy of bamlanivimab in outpatient (not hospital) settings. People in the study were given an IV infusion of the drug within 3 days of having a positive COVID-19 test. Participants were randomized to an infusion of a placebo or one of three doses of the bamlanivimab (700 mg, 2800 mg, 7000 mg). Neither the investigators nor trial participants knew which group they were in.
Trial participants could only have mild or moderate symptoms (like fever, cough, sore throat) and most people only had mild symptoms. Importantly, people who were pretty sick (low oxygen, breathing fast or hard, or had very high heart rates) were not included in the trial. Over 2/3 of both groups had individuals with risk factors for severe COVID-19, but only a small percentage of study participants were older than 65 and the study investigators could choose to exclude participants with “any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator should preclude participation.” That’s pretty darn vague and gives the investigators a lot of leeway.
What did they find? The amount of virus detected by nasopharyngeal swab at Day 11 of the trial was less for individuals who received the 2800 mg dose of bamlanivimab than among placebo treatment participants. There was no difference between the 700 mg and 7000 mg dose participants from the placebo group.
Sounds great, right? EXCEPT, this is what is called disease-oriented evidence (or DOEs). This kind of evidence gives you information that is not particularly meaningful to actual people and doesn’t tell you if anyone felt or got any better. What we want is “patient-oriented evidence.” This is evidence about outcomes that matter to real people. Examples of patient-oriented evidence (or POEs) include: do people live longer, stay out of the hospital, or have improvement in symptoms? The study looked at these as well but did not have enough people or enough events (like hospitalizations or deaths) to draw any meaningful conclusions. That’s a big question mark remaining.
Lucky for you, the second study is much quicker to go through! This study is a part of the Accelerating COVID-10 Therapeutic Interventions and Vaccines Program (ACTIV-3). They randomized patients hospitalized with COVID-19 to bamlanivimab or placebo. This study was stopped early because there was no clinical benefit seen in hospitalized patients.
All that to say, bamlanivimab doesn’t work for people who are sick enough to be in the hospital and we need more information for folks with mild to moderate symptoms. We need to know more about those POEs before declaring bamlanivimab a success.
There are some major hurdles for this drug as well. It requires an IV infusion (which many clinician’s offices are not set up to do). There are limited amounts of drug available. And it is only studied in folks who are very early on in their illness (the study median was 4 days from symptom onset). Delays in testing and getting results from those tests might limit the usefulness of this drug should it prove to be effective.
The FDA EUA says that due to this lack of evidence and limitations on supplies, this should only be given to be who are high risk and should not be the “standard of care.” They do give some guidance on who can get bamlanivimab currently. This includes people are older or have chronic medical problems (like diabetes or have weakened immune systems). If you have COVID-19 and want to know if this is something for you to consider, talk to your primary care clinician.
The NIH has COVID-19 Treatment Guidelines with evidence reviews
You can also read the BLAZE-1 published study results
