Overview and Background

Bamlanivimab and etesevimab are antibody drugs approved for use in combination for people who are infected with SARS-CoV2 (the virus that causes COVID-19).

Categorized as monoclonal antibody treatments (mAbs), bamlanivimab and etesevimab are produced in a laboratory and currently produced by Eli Lilly and Company.

Engineered with a very specific three-dimensional shape, bamlanivimab and etesevimab are designed to attach directly to a protein on the SARS-CoV2 virus called the spike protein. The SARS-CoV2 virus uses this spike protein to enter the cell and attach to a specific cell protein called ACE-2.

Once the SARS-CoV2 virus is inside an infected cell it reproduces and then spreads to other cells.

By attaching to the spike protein, bamlanivimab and etesevimab effectively cover the part of the spike protein, preventing the SARS-CoV2 from attaching to ACE-2 found in cells of the body.

Since bamlanivimab and etesevimab work well in this application, the idea is to give it to people who are in the early stages of COVID-19 in an effort to prevent it from progressing to more severe illness. Doctors are also considering giving these antibodies to people who have been exposed to, but do not yet have, COVID-19.

Because the virus attaching to ACE-2 is initially what starts the process that leads to severe COVID-19, scientists believe that giving it to people who have been exposed or who are in the early stages of COVID-19 can interrupt attachment to ACE-2. If the interaction with ACE-2 is interrupted and doesn’t happen then the virus may only cause mild symptoms characterized by irritating your upper respiratory track, as in any cold.

Scientists are also learning that certain variants of the SARS-CoV2 virus are not neutralized as easily, or as completely, as other variants. This means that bamlanivimab and etesevimab tend to work better against some variants and not so well against others.

In December 2021, pre-print data (data that have not yet gone through the scientific review process) posted by scientists in Europe suggests that the potency of bamlanivimab and etesevimab are much lower against Omicron (the highly contagious variant that was discovered in November 2021) compared with other known variants.

Scientists are also discovering that certain variants of the SARS-CoV2 virus are not neutralized as easily, or as completely, as other variants. In this regard, bamlanivimab/etesevimab works better against some variants than it does for others. Bamlanivimab/etesevimab does not work well against Omicron, the highly contagious variant of COVID-19 that was discovered in November 2021.

Appropriate Patients for Bamlanivimab/Etesevimab

Bamlanivimab/etesevimab is for people with mild to moderate COVID-19 who also are at risk for developing severe disease. In such people, research suggests that bamlanivimab/etesevimab can reduce the need for hospitalization by 70 percent. As of late 2021, experts are also discussing the possibility of giving the drug to those considered high-risk who do not have COVID-19 but have been exposed.

Bamlanivimab/etesevimab are intended for people with mild to moderate COVID-19 who also are at risk of progressing to severe disease. In such people, research suggests that bamlanivimab/etesevimab can reduces need for hospitalization by up to 70%. In addition, and as of late 2021, health experts continue to discuss the possibility of administering bamlanivimab/etesevimab to those considered high-risk and have been exposed, but do not have COVID-19.

Mild to moderate COVID-19 means that you have tested positive for SARS-CoV2 and have some symptoms, but do not require supplemental oxygen because of the infection. Supplemental oxygen means oxygen received through a tube in the nose or through a face mask, or through a high-low device. If you already breathe supplemental oxygen for another condition and do not have an increased need for oxygen resulting from COVID-19, you may also qualify for antibody treatment.

Bamlanivimab/etesevimab can only be administered to those are age 2 and older who are not hospitalized for COVID-19. For bamlanivimab/etesevimab to be most effective, you should receive it within 10 days of the start of your symptoms. If possible, it’s even better to receive it within 5 days of the onset of your symptoms.

In addition, and as of late 2021, health experts continue to discuss the possibility of administering bamlanivimab/etesevimab to those considered high-risk and have been exposed, but do not have COVID-19.

Take home message: Treatment of COVID-19 with bamlanivimab/etesevimab appears to be most effective for people who are experiencing mild symptoms and are at risk for becoming much sicker.

A person is considered at risk for developing severe disease, and qualified for bamlanivimab/etesevimab, if he or she has at least one of these risk factors:

• Age 65 years or older

• Overweight or obese

• Pregnancy

• Chronic kidney disease

• Diabetes mellitus

• Immunosuppression (meaning a disease or treatment that weakens your immune system)

• Cardiovascular disease (including congenital heart disease or high blood pressure)

• Chronic lung diseases (including chronic obstructive pulmonary disease (COPD), moderate to severe asthma, and cystic fibrosis*).

• Sickle cell disease

• Problems with the nervous system that appeared at birth or in childhood

• Dependence on a medical technology (including a hole in your windpipe to help you breathe, a feeding tube into your stomach, and positive pressure ventilation for a reason other than COVID-19 - such as for sleep apnea)

* People with mild, well-controlled asthma are not considered at high risk of developing severe COVID-19.

You might notice that pregnancy is considered as a risk factor for developing severe COVID-19. This means that simply being pregnant qualifies you to receive bamlanivimab/etesevimab for non-hospitalized COVID-19, even if you are otherwise healthy; reasons for this include:

• If infected, pregnancy increases your risk of developing severe COVID-19.

• COVID-19 puts your fetus at risk.

• The possibility that some bamlanivimab/etesevimab antibodies will pass through the placenta, giving the fetus some protection from the virus.

All of this means that pregnancy is more of a reason to receive monoclonal antibody treatment than to avoid it.

As for nursing mothers, it is unlikely that your newborn will absorb any antibodies that make it into your breastmilk. However, in the case that antibodies do make it all the way to the newborn’s blood, they would be helpful in providing added protection to the fetus.

How Bamlanivimab/Etesevimab is Administered

Bamlanivimab/Etesevimab is administered intravenously (IV). This means that a needle attached to a tube is inserted into a vein (usually in your arm) and a liquid that has the drug dissolved into it is infused from a bag through the tube and into the body.

In the case of Bamlanivimab/Etesevimab treatment for COVID-19, a single infusion is given one time and within ten days of your first symptoms (the treatment is even more effective if administered within five days of initial onset of symptoms). Bamlanivimab/Etesevimab IV infusion is typically provided at a hospital or at an infusion center.

In December 2021, another mAb drug combination – Regeneron’s casirivimab/imdevimab - was determined to be able to be administered by IV infusion and subcutaneously (SQ). Currently, health experts are evaluating the possibility of also administering bamlanivimab/etesevimab subcutaneously. If deemed appropriate, bamlanivimab/etesevimab would be able to be administered as a series of four subcutaneous (SQ) injections under the skin, all at the same appointment.

Since subcutaneous administration typically requires less training and equipment than what is required by IV infusion, it can be administered in a wide variety of settings, including doctors’ offices, pharmacies, and community centers.

Limitations of Bamlanivimab and Etesevimab

As of December 2021, interest in using bamlanivimab/etesevimab demonstrated a significant decline, due primarily to the finding that these mAbs do not appear to be highly effective in protecting against the highly contagious COVID-19 Omicron variant.

Currently, health experts direct people to defer COVID-19 vaccine shots after they receive COVID-19 monoclonal antibodies. As of January 2022, the United States Center for Disease Control and Prevention (CDC) recommends deferring COVID-19 vaccination for a period of 90 days after receiving bamlanivimab/etesevimab.

Side effects of the treatment tend to be mild and include things like mild bleeding, bruising, pain, soreness, or swelling at the site of IV infusion.

References

Dougan M, Nirula A, Azizad M, et al; BLAZE-1 Investigators. Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19.N Engl J Med . 2021 Oct 7;385(15):1382-1392. doi: 10.1056/NEJMoa2102685. Epub 2021 Jul 14. PMID: 34260849; PMCID: PMC8314785.

National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. Retrieved December 26, 2021

US Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization (EUA) of bamlanivimab and etesevimab. Accessed Decembern29, 2021