Overview and Background

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

Categorized as monoclonal antibody treatments (mAbs), casirivimab and imdevimab are produced in a laboratory and currently produced by Regeneron as a combination drug under the trade name REGENCOV.

Engineered with a very specific three-dimensional shape, casirivimab and imdevimab 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, casirivimab and imdevimab effectively prevents the SARS-CoV2 from attaching to ACE-2 found in cells of the body.

Effects of Casirivimab and Imdevimab on COVID-19

When antibodies, like casirivimab and imdevimab, attach to the spike protein of the virus, scientists say that the virus is neutralized. Being neutralized can mean that the virus cannot attach to ACE-2 and infect other body cells. Sometimes, neutralized can also mean that the virus cannot spread to other people.

Scientists are learning that it is easier to neutralize the SARS-CoV2 virus against attaching to ACE-2 and infecting cells of an infected person than it is to neutralize it against spreading to other people.

In the case of casirivimab and imdevimab, the main goal has been to neutralize the virus by preventing it from attaching to ACE-2.

Since casirivimab and imdevimab 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 casirivimab and imdevimab 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 casirivimab and imdevimab are much lower against Omicron (the highly contagious variant that was discovered in November 2021) compared with other known variants.

Appropriate Patients for Casirivimab/Imdevimab

Casirivimab/imdevimab are intended for people with mild to moderate COVID-19 who also are at risk of progressing to severe disease. In such people, research conducted by the Mayo Clinic suggests that casirivimab/imdevimab dramatically reduces need for hospitalization and the rate of death from COVID-19. In addition, and as of late 2021, health experts continue to discuss the possibility of administering casirivimab/imdevimab 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.

Casirivimab/imdevimab can only be administered when the person is not hospitalized for COVID-19. For casirivimab/imdevimab 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 casirivimab/imdevimab to those considered high-risk and have been exposed, but do not have COVID-19.

Take home message: Treatment of COVID-19 with s casirivimab/imdevimab 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 casirivimab/imdevimab, 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 casirivimab/imdevimab 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 casirivimab/imdevimab 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 Casirivimab/Imdevimab Are Administered

Casirivimab/imdevimab is most often 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. Typically, intravenous administration of Casirivimab/imdevimab takes about 30 minutes from start to finish.

After administration, you need to remain under supervision of your health care provider for roughly an hour to ensure there are no adverse effects associated with the treatment

In the case of Casirivimab/imdevimab 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). Casirivimab/imdevimab IV infusion is typically provided at a hospital or at an infusion center.

Alternatively, casirivimab/imdevimab can be given 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 Casirivimab/Imdevimab

As of December 2021, interest in using casirivimab/imdevimab 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 casirivimab/imdevimab.

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

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

O'Brien MP, Forleo-Neto E, Musser BJ et al.; Covid-19 Phase 3 Prevention Trial Team. Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19. N Engl J Med. 2021 Sep 23;385(13):1184-1195. doi: 10.1056/NEJMoa2109682. Epub 2021 Aug 4. PMID: 34347950; PMCID: PMC8362593.

Planas et al. Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization. PREPRINT on bioRxiv. Accessed December 29, 2021

Razonable RR, Pawlowski C, O'Horo JC et al. Casirivimab-Imdevimab treatment is associated with reduced rates of hospitalization among high-risk patients with mild to moderate coronavirus disease-19. EClinicalMedicine. 2021 Oct;40:101102. doi: 10.1016/j.eclinm.2021.101102. Epub 2021 Aug 30. PMID: 34485873; PMCID: PMC8404031.

US Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization (EUA) of REGEN-COV (casirivimab and imdevimab). Accessed December 29, 2021