Is the monoclonal antibody bamlanivimab a miracle drug?

The feeling I get is usually a mix of despair, anger, and foreboding. It typically starts with a conversation, email, or social media post by someone that is to the far extreme of asinine. These statements, at any other time in history, would make much chuckle and shake my head but this is not any other time in history. This is a time where misunderstanding and misinformation leads to ever more annoyance, suffering, and death as it fuels the fire of the pandemic. This is a time where such statements make me feel ill physically and emotionally. That was my headspace when I recently learned that some families with a child sick with COVID were intentionally getting the entire household infected to decrease their quarantine times. If that was not enough I was blamed for this behavior because I have advocated that schools follow expert guidelines on safe practices.

Let me try to break that down for you, and sometimes following such logic is difficult. The argument, as far as I can tell, is that the difficulties of quarantine and isolation are forcing families to go to the extreme of infecting themselves and therefore the restrictions should be eased. So, in order to prevent careless and reckless people from putting their own families, neighbors, and friends at risk we should stop being so strict. The fact that this would create a situation where people who are careful and thoughtful are put at risk did not bother the proponent of this line of attack. I know it’s hard to follow. After a while I stopped trying to make sense of it.

I hear things like this all the time and I just don’t know how to respond. When people are willing to think that the recommendations of every reputable medical, scientific, and public health body are wrong and somehow they, after a thorough internet and social media search, have the unspoken truth, I worry there is no hope for us.

This social media driven atmosphere has also driven the public response to all potential drug treatments for COVID-19 in a way that causes great confusion and consternation. The timeline of COVID-19 treatment insanity is as follows:

1. Animal or cell research shows Drug X blocks some part of SARS-CoV2 activity.
2. Small human studies show benefit but the studies are poorly designed or too small to be conclusive.
3. News or social media reports this as a new breakthrough drug. They are particularly fond of the phrase “game changer” which now turns my stomach every time I hear it.
4. The FDA allows for an emergency use authorization (sometimes under political pressure) to use the drug in a specific group of people.
5. People are prompted by these reports to call me and other doctors asking about this treatment and how they can get it.
6. People attempt to skirt the EUA restrictions and get the medication even if they don’t qualify.
7. Doctors and scientists are not convinced that the drug is as great as touted in social media forums or in the news (if it works at all) and call for some restraint and more research.
8. People (and sometimes politicians) express outrage at this with accusations of a conspiracy to suppress this needed treatment. Some fringe doctors produce impassioned online videos with claims of 100% cure rates. The flames are fanned.
9. More and better quality research is done showing the medication was not as effective as previously thought, only effective in a small subgroup of individuals, or not effective at all.
10. A new drug catches people’s fancy and the cycle repeats.

(The only drug that has not followed this trend thus far has been dexamethasone which you can read about here).

The newest kid on the block to enter the pathway is the monoclonal antibody treatment named bamlanivimab.  Since bamlanivimab’s pronunciation takes hours to master, let’s call it bam-bam. A monoclonal antibody is a specific antibody targeted to a very specific site that is manufactured in high titers. In this case bam-bam is an antibody designed to attach to the spike protein of the SARS CoV-2 virus and neutralize it. 

In theory, the ability to manufacture an antibody against the virus would be a silver bullet targeted therapy that could completely prevent infection caused by SARS-CoV2 and that’s exactly what it did… in monkeys. While monkeys are biologically, and, for some, psychologically, very similar to humans the results are not necessarily applicable to humans in real life. The research was designed such that the medication was given just after the monkeys were infected at a known time with a known quantity of virus. This obviously does not reflect the reality for humans who can be infected with varying quantities of virus at unknown times. This prompted human studies, of which there have now been two.

The first study involved giving bam-bam to patients hospitalized with COVID-19.  This trial was stopped early because it was clear that there was no benefit.  This was not published in a scientific journal but was reported in a press release by the pharmaceutical company.

The second was a phase II clinical trial that divided 452 patients into four groups. One group was given a placebo and three other groups were given escalating doses of bam-bam.  The primary goal of the study was to measure how the medication decreased viral levels. 

It would be expected that giving an antibody that neutralizes virus would decrease viral levels. It would also be expected that increasing doses would lead to a better result. This is not what happened. First, when all patients who received the drug were combined, there was no difference in viral levels compared to the placebo. When analyzed by dose, there was a decrease in viral levels in those who received the middle dose which was not statically significant when adjusting for confounding variables. It is far more likely that this result was due to chance because it doesn’t make sense why the middle dose would be effective but the higher dose would not.

Other secondary findings, however, were a bit more promising. There was a decrease in the number of people who were either hospitalized or who had to go to the ER from 6.3% to 1.6%. There was no clear decrease in hospitalizations alone so they combined hospitalizations and ER visits after the data was collected which is a bit sketchy in my opinion.  Further there were a small number of patients and very few hospitalizations or ER visits  precluding definitive conclusion.  In a post hoc analysis of people over 65 and those with a BMI over 35 the drop was from 15% to 4%. A post hoc analysis means that the analysis was done after the data set was seen.  This analysis was not planned before the experiment and raises some questions about reliability. Also, for the primary endpoint of decrease in viral load they separated the doses, but for the secondary endpoint they combined all doses. This would mean that the doses that don’t drop the viral levels somehow improve other outcomes. This seems unlikely.

Based on the post-hoc results the emergency use authorization was only for high risk people with proven COVID-19 who are not on oxygen and within 10 days of their symptom onset.  This is because low risk people are more likely to recover on their own making the medication less likely to be beneficial for them. High risk is defined as someone with

• a body mass index (BMI) ≥35
• chronic kidney disease
• diabetes
• immunosuppressive disease or currently receiving immunosuppressive treatment
• Are ≥65 years of age
• Are ≥55 years of age AND have
  • cardiovascular disease, or
  • hypertension, or
  • chronic obstructive pulmonary disease/other chronic respiratory disease.

There are ongoing trials but the company is no longer studying it alone, they are now combining it with another monoclonal antibody.  This speaks of a lack of confidence in the drug by itself by Eli Lilly.

The bottom line is that this bamlanivimab is promising and, while I truly hope it is beneficial, based on the data published thus far it is far from a miracle drug.  Would you sit for an hour and perhaps spend a few hundred dollars for a copay to decrease your risk of hospitalization from 6 in 100 to 1 in 100? How about from 15 in 100 to 4 in 100? This is not a reduction in the chance of dying but in the chance of need to go to the ER (or perhaps be admitted to the hospital). I’m not sure. So, if we go back to the timeline of COVID-19 treatment insanity, we are now at step seven. Let the social media rampage rage on…