Monoclonal Antibody Treatment

Under section 564 of the Federal Food, Drug & Cosmetic Act, the FDA may, pursuant to a determination and declaration by the HHS Secretary, authorize an unapproved product or unapproved uses of an approved product for emergency use. In issuing an EUA, the FDA must determine, among other things, that the product may be effective in diagnosing, treating, or preventing a serious or life-threatening disease or condition caused by a chemical, biological, radiological, or nuclear agent; that the known and potential benefits outweigh the known and potential risks for the product; and that there are no adequate, approved, and available alternatives. Emergency use authorization is NOT the same as FDA approval or licensure.

The EUA authorizes casirivimab and imdevimab, known as REGEN-COV, manufactured by Regeneron Pharmaceuticals Inc. (Regeneron), for emergency use in adults and pediatric patients who are 12 years of age and older weighing at least 88 pounds, and who are at high risk for severe COVID-19, including hospitalization or death for:

• The treatment of mild to moderate symptoms of COVID-19
• Post-exposure prophylaxis of COVID-19 in those who are not fully vaccinated OR those who are not expected to build up enough of an immune response once fully vaccinated AND have been exposed to someone infected with the virus or who is at high risk of being exposed.

High risk for progressing to severe COVID-19 and/or hospitalization is defined as patients who meet at least one of the following criteria

• Are ≥65 years of age
• Have a body mass index (BMI) ≥35
• Are pregnant
• Have chronic kidney disease
• Have diabetes
• Have an immunosuppressive disease
• Are currently receiving an immunosuppressive treatment
• Have cardiovascular disease or hypertension
• Have chronic lung diseases
• Have sickle cell disease
• Have neurodevelopmental disorders or conditions that confer medical complexity
• Have a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation

Yes. REGEN-COV is not authorized for use in patients:

• Who are hospitalized due to COVID-19, OR
• Who require oxygen therapy due to COVID-19, OR
• Who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.

A benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation.

Post-exposure prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19. REGEN-COV is not authorized for pre-exposure prophylaxis for prevention of COVID-19.

Yes, casirivimab and imdevimab are monoclonal antibodies. Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance, or mimic the immune system's attack on cells. They are designed to block viral attachment and entry into human cells, thus neutralizing the virus. They are designed to limit viral replication and may be effective for the treatment of COVID-19 in patients who are at high risk for progressing to severe COVID-19 and/or hospitalization.

It is recommended REGEN-COV be administered as soon as possible after a positive viral test for SARS-CoV-2 and within 10 days of symptom onset. It is administered as a single dose of 600 mg of casirivimab and 600 mg of imdevimab via a single IV infusion or subcutaneous injection.

In the case of usage as a post-exposure prophylaxis, REGEN-COV should be administered as a single dose of 600 mg of casirivimab and 600 mg of imdevimab via a single IV infusion or subcutaneous injection as soon as possible following exposure to SARS-CoV-2.

For those in whom repeat dosing is determined to be appropriate for ongoing exposure to SARS-CoV-2 for longer than four weeks AND who are not expected to mount an adequate immune response to complete vaccination, the initial dose is followed by subsequent repeat dosing of 300 mg of casirivimab and 300 mg of imdevimab by subcutaneous injection or intravenous infusion once every four weeks for the duration of ongoing exposure.

More information about administration is available in the Health Care Provider Fact Sheet.

REGEN-COV may only be administered in settings in which healthcare providers would have immediate access to medications to treat a severe infusion reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS) as necessary. Please speak with your doctor or contact your local or state public health department for more information.

No. REGEN-COV is an investigational drug. It is not currently FDA-approved to treat any diseases or conditions, including COVID-19. However, upon issuance of the EUA, REGEN-COV is authorized for emergency use for the treatment of mild to moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing who are 12 years of age and older weighing at least 88 pounds, and who are at high risk for progressing to severe COVID-19 and/or hospitalization and as a post-exposure prophylaxis in those who are not fully vaccinated against COVID-19 OR those who are not expected to build up enough of an immune response to vaccination AND have been exposed to someone who is infected with SARS-CoV-2 OR are at high risk of being exposed to someone infected with SARS-CoV-2.

Yes, bamlanivimab may be used in patients hospitalized for reasons other than COVID-19, so long as the terms and conditions of authorization are met. For example, a patient hospitalized for an elective orthopedic procedure who reports mild symptoms of COVID-19, confirmed with positive results of a direct SARS-CoV-2 viral test, may be appropriate for treatment with bamlanivimab if the patient is also at high risk for progressing to severe COVID-19 and/or hospitalization, as detailed in the Health Care Provider Fact Sheet.

Specifically, bamlanivimab is authorized for emergency use for the treatment of mild to moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing who are 12 years of age and older weighing at least 40 kg, and who are at high risk for progressing to severe COVID-19 and/or hospitalization.

Bamlanivimab is not authorized for use in patients:

• who are hospitalized due to COVID-19, or
• who require oxygen therapy due to COVID-19, or
• who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.

Possible side effects of REGEN-COV are:

• Allergic reactions: Allergic reactions can happen during and after infusion or injection of REGEN-COV. Tell your healthcare provider right away or seek immediate medical attention if you get any of the following signs and symptoms of allergic reactions: fever, chills, nausea, headache, shortness of breath, low or high blood pressure, rapid or slow heart rate, chest discomfort or pain, weakness, confusion, feeling tired, wheezing, swelling of your lips, face, or throat, rash including hives, itching, muscle aches, feeling faint, dizziness and sweating. These reactions may be severe or life threatening.
• Worsening symptoms after treatment: You may experience new or worsening symptoms after infusion or injection, including fever, difficulty breathing, rapid or slow heart rate, tiredness, weakness or confusion. If these symptoms occur, contact your healthcare provider or seek immediate medical attention as some of these symptoms have required hospitalization. It is unknown if these symptoms are related to treatment or are due to the progression of COVID-19.

The side effects of getting any medicine by vein may include brief pain, bleeding, bruising of the skin, soreness, swelling, and possible infection at the infusion site. The side effects of getting any medicine by subcutaneous injection may include pain, bruising of the skin, soreness, swelling, and possible infection at the injection site.

Yes. As part of the EUA, FDA is requiring health care providers who prescribe REGEN-COV to report all medication errors and serious adverse events considered to be potentially related to REGEN-COV through FDA's MedWatch Adverse Event Reporting program. Providers can complete and submit the report online; or download and complete the form, then submit it via fax at 1-800-FDA-0178. This requirement is outlined in the EUA's health care provider Fact Sheet.

No, reporting of patient outcomes is not required under the EUA. However, reporting of all medication errors and serious adverse events considered to be potentially related to REGEN-COV occurring during REGEN-COV treatment is required.