Monoclonal antibodies: Uses, common brands, and safety info

CORONAVIRUS UPDATE: As experts learn more about the novel coronavirus, news and information changes. For the latest on the COVID-19 pandemic, please visit the Centers for Disease Control and Prevention.

Beginning with the discovery in 1986 of the drug muromonab-CD3 for use in preventing tissue rejection in liver transplant patients, monoclonal antibodies, or mAbs, have become an important treatment option for a variety of diseases. MAb drugs have been approved for conditions as varied as rheumatoid arthritis, osteoporosis, asthma, high blood cholesterol, Crohn’s disease, and even the Ebola virus. 

In the late 1990s the first mAb for the treatment of cancer, Rituxin (generic name rituximab) was approved by the U.S. Food and Drug Administration (FDA). Since that time, dozens of mAbs for use as cancer treatments, or antineoplastics, have been discovered. The use of mAb therapy is now a main component of cancer therapy, along with surgery, radiation, and chemotherapy.

Most recently, monoclonal antibody therapies have been in the news to treat COVID-19 under FDA emergency use authorization (EUA). As of the published date of this article, they have not yet received full FDA approval.

Below are common examples, although not a complete list, of mAbs used for treating various diseases including cancers followed by information on how they work, what conditions they treat, safety, and cost.

Other monoclonal antibodies

REGEN-COV (casirivimab and imdevimab, administered together), bamlanivimab and etesevimab (administered together), and sotrovimab are mAbs that have not been FDA approved, however, because of the public health need they have been authorized for emergency use in COVID-19 patients by the FDA under an emergency use authorization (EUA). An EUA is an action the FDA can take to make certain medical products available in emergency situations, such as a pandemic, when there are no adequate FDA-approved options.

• REGEN-COV, made by Regeneron Pharmaceuticals, is authorized for emergency use as post-exposure prevention for COVID-19 in adults and children 12 years of age and older who are at high risk for progression to severe COVID-19, including hospitalization or death. REGEN-COV also is authorized for the treatment of mild-to-moderate COVID-19 in adults and children 12 years of age and older with a positive COVID-19 test result who are at high risk for progression to severe COVID-19. It is not authorized for pre-exposure use to prevent COVID-19 before being exposed to the SARS-CoV-2 virus—only after exposure to the virus.

• Sotrovimab, developed by GlaxoSmithKline and Vir Biotechnology, is authorized under an EUA and may be effective for the treatment of COVID-19 in adults and certain pediatric patients 12 years and above with mild-to-moderate COVID-19 symptoms.

• The combined administration of bamlanivimab and etesevimab, made by Eli Lilly and Co., is authorized under an EUA for use following exposure to the virus for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg), with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

What are monoclonal antibodies?

Antibodies are protective proteins produced by the body’s immune system in response to the presence of a foreign substance, called an antigen. Antigens resulting in an immune response include disease-causing organisms and toxic materials such as bacteria, fungi, parasites, viruses, and chemicals. 

When an antigen enters the body, the immune system is able to recognize it as foreign. To eliminate it, specialized white blood cells called B lymphocytes, or B cells, produce antibodies specific to that antigen. As antibodies come in contact with the invading antigens, they then work by various means neutralizing them.  

Medical scientists have learned to produce antibodies in the lab that mimic the action of natural antibodies. These man-made, or synthetic, antibodies are produced by introducing human genes into mice, or another suitable host, who are then exposed to the specific antigen they want to produce antibodies against. The immune cells of the host animal then produce the desired human antibody. These antibodies are called monoclonal antibodies because they are cloned from only one type of cell in order to target one specific antigen.

How do monoclonal antibodies work?

MAb therapies restore, mimic, inhibit or enhance the body’s immune system. They may work in one or multiple ways, depending on the antigen they are targeting. The role of the mAb may include one or more of the following actions: 

• Attaching to the antigen to flag it allowing the body’s natural antibodies to more easily find and neutralize

• Blocking cell growth

• Blocking antigens that prevent the natural immune system from working

• Attacking cancer cells directly

• Binding antigens to the body’s immune cells to improve their protective action

• Blocking a virus from attaching to human cells

• Blocking the proteins responsible for destroying healthy tissue

What are monoclonal antibodies used for?

The use of monoclonal antibodies to treat diseases is called immunotherapy because they treat diseases by activating or suppressing the body’s own immune system. Each individual monoclonal antibody will target a specific antigen in the body. Uses for monoclonal antibodies include the following.

Cancers

When a human cell goes through a genetic mutation that leads to uncontrolled growth, the body’s immune system can usually detect it and prevent, repair, or destroy the mutated cells. There are times when cancerous cells trick the body to avoid detection allowing them to grow unchecked or the cancer cells may weaken the body’s immune system so that it cannot effectively fight the disease. Cancerous conditions treated by mAbs include:

• Leukemia

• Glioblastoma

• Colorectal cancer

• Ovarian cancer

• Head and neck cancer

• Melanoma

• Kidney cancer

• Liver cancer

• Multiple myeloma

• Gastrointestinal (GI) cancer

• Lymphoma

• Mesothelioma

• Cervical cancer

• Breast cancer

• Lung cancer

• Esophageal cancer

RELATED: Leukemia vs. lymphoma

Autoimmune disorders

There are times when the body mistakenly identifies normal tissues as foreign, i.e., as an antigen, and produces antibodies against the tissue. This “mistaken identity” causes autoimmune disorders. Monoclonal antibodies can help blunt the body’s attack on its own tissues by blocking the proteins responsible for destroying the healthy tissue. Autoimmune disorders treated by mAbs include:

• Rheumatoid arthritis

• Multiple sclerosis

• Lupus

• Crohn’s disease

• Ulcerative colitis

• Psoriasis 

• Psoriatic arthritis

RELATED: 8 common types of arthritis

COVID-19

REGEN-COV and sotrovimab, the two monoclonal antibody treatments available under the FDA’s EUA, mimic the function of the body’s immune system by blocking the ability of the coronavirus to enter human cells. This can help slow the spread of the COVID-19 infection and potentially reduce the length and severity of symptoms.

Other conditions

• Simulect (basiliximab) is given along with other medications to kidney transplant patients to prevent organ rejection. Simulect works by slowing down the body’s immune system to prevent the body from rejecting the new tissue following transplant surgery.

• Prolia (denosumab) is given to women with osteoporosis, a condition in which the bones become brittle, to reduce the risk of fractures. Prolia prevents certain cells in the body from breaking down bone.

• Xolair (omalizumab) reduces asthma attacks by preventing the allergic reactions caused by the allergens.

Who can take monoclonal antibodies?

Adults

Adults can take mAbs for a variety of conditions and they are generally well tolerated. Administration of mAbs does present the risk of infusion reactions and immune reactions such as acute anaphylaxis, a serious allergic reaction. Caution should be used if a patient is suspected of having a hypersensitivity to any active or inactive ingredient in the drug. 

Seniors

Seniors can use mAbs when appropriate. Many of the targeted diseases, e.g., osteoporosis and certain cancers, are more commonly found in older patients.

Children

Some mAbs have approved uses in infants, children, and adolescents based on the targeted disease. For example, mAbs for treating juvenile arthritis have been approved for use in patients as young as 2 years of age.

Regarding children and COVID-19, as of the date this article is published, there is insufficient evidence to recommend either for or against the use of monoclonal antibody products. Based on adult studies, mAbs may be considered on a case-by-case basis for non-hospitalized children who are at high risk of severe disease or are age 16 years or older.

Pregnant and breastfeeding women

In general, mAbs have not been adequately studied in pregnant women and they should be used only if the benefits outweigh the risks. Individual mAb drugs may be harmful to the fetus because of their mechanism of action or from data obtained from animal studies. It is not known whether mAbs are present in breast milk and their use is discouraged in women who are breastfeeding. A woman’s healthcare provider is the best source of information when managing mAb treatment when pregnant or breastfeeding.

Are monoclonal antibodies safe?

Black box warnings

Due to the wide range of approved conditions treated, there is a wide variety of potential adverse effects related to mAbs. These include more serious adverse events that resulted in FDA-mandated “boxed warnings,” also called black box warnings. A study published in the Journal of Allergy and Clinical Immunology in February 2021 found that of the 83 FDA-approved mAbs available in the U.S. in 2020, 33 had boxed warnings highlighting serious adverse events. The serious adverse events compiled from the clinical trials information for several mAbs include the following:

• Immune reactions including acute anaphylaxis (severe allergic reaction) and systemic inflammatory response syndrome (a condition in which there is inflammation throughout the entire body)

• Reactivation of infections including tuberculosis and other bacterial, fungal, and viral infections 

• Blood toxicities such as thrombocytopenia (deficiency of platelets in the blood)

• Autoimmune diseases such as lupus-like syndromes, thyroid disease, and colitis (inflammation of the inner lining of the colon)

• Cancers such as lymphomas

• Dermatitis (dry skin, itching, and redness)

• Cardiovascular toxicity, such as cardiac failure 

• Cytokine storm (a severe immune reaction in which the body releases too many cytokines into the blood too quickly causing high fever, inflammation, and severe fatigue and nausea)

Recalls

There are no current mAb recalls as of August 2021.

Restrictions

In general, use caution when considering mAb therapy if the patient has any of the following conditions:

• Known hypersensitivity to the drug

• Current or recurrent serious infectious diseases

• Active or latent tuberculosis infection

• Pre-existing hypertension (high blood pressure) or risk factors for hypertension

Are monoclonal antibodies controlled substances?

No, monoclonal antibodies are not controlled substances.

Common monoclonal antibodies side effects

MAbs are injectable proteins so it is not uncommon for patients to experience an allergic reaction at the injection site. As mentioned above, mAbs can cause a variety of side effects based on the specific drug and the targeted condition treated. Following are general common side effects common to mAbs:

• Fever

• Chills

• Weakness

• Headache

• Nausea

• Vomiting

• Diarrhea

• Low blood pressure

• Rashes

• Diarrhea

• Itching

• High blood glucose levels

• Increased triglyceride levels

• Cough

• Constipation

• Shortness of breath

• Peripheral edema

• Headache

• Fever

• Muscle aches and pain

• Decreased appetite

• Insomnia

• Abdominal pain

• Back pain

• Dizziness

How much do monoclonal antibodies cost?

Monoclonal antibodies are some of the most expensive drugs available. According to a recent study published in the American Journal of Managed Care, the average annual price of mAb therapy was $96,731, however, there is a significantly higher cost for some therapeutic areas, such as oncology (cancer) drugs. Prices for mAbs for conditions such as psoriasis are much less than the average, although still expensive at approximately $20,000 for a year’s treatment. These costly drugs are often less expensive with insurance coverage, through the patient support programs offered by many manufacturers, or with a free SingleCare discount card.