REGEN-COV (casirivimab with imdevimab to be administered together) has not been approved, but has been authorized for emergency use by FDA, 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 progressing to severe COVID-19 and/or hospitalization.
This use is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use under section 564(b)(1) of the Food Drug and Cosmetic Act, unless the authorization is terminated or revoked sooner.
Frequently Asked Questions
Select a category to see specific questions and answers.
Access and Reimbursement
What is an Emergency Use Authorization (EUA)?
An EUA allows the U.S. Food and Drug Administration (FDA) to help strengthen the nation’s public health protections against chemical, biological, radiological and nuclear (CBRN) defense threats by facilitating the availability and use of therapies needed during public health emergencies.
Under section 564 of the Federal Food, Drug, and Cosmetic Act, the FDA Commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when there are no adequate, approved, and available alternatives.
Is there a list of centers where REGEN-COV is available?
Details on infusion centers where antibody therapies, including REGEN-COV, may be available can be found on the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR) and the National Infusion Center Association (NICA)* site locators.
*IMPORTANT INFORMATION: Infusion sites displayed in this tool have been authorized to administer antibody treatments for COVID-positive patients under Emergency Use Authorization. These antibody therapies are restricted to certain high-risk patients and require a drug order (similar to a prescription) from a Health Care Provider (HCP) for eligible patients. HCPs must verify eligibility of their patients and verify the availability of doses at an authorized infusion site before they refer an eligible patient to schedule an appointment to receive treatment at an authorized infusion site.
Please note that the inclusion of a site does not imply current availability of doses. More states and locations are regularly being added. If not yet listed, ambulatory centers or other administration sites should contact their state health departments.
Who determines which infusion sites receive REGEN-COV?
Treatment sites must order REGEN-COV directly from AmerisourceBergen Corporation, the drug’s sole distributor. Approval of sites to receive product will be determined by AmerisourceBergen Corporation in conjunction with the United States government.
How do I order/re-order REGEN-COV?
To order REGEN-COV, treatment sites should contact AmerisourceBergen Corporation directly at [email protected] Treatment sites can also review the direct ordering process guide, and fill out a C19 Therapies Direct Order Request located here.
What is the coverage and reimbursement for REGEN-COV?
REGEN-COV is free of charge to requesting treatment sites, as the United States government is paying for the product. The combination therapy must be administered via a single intravenous infusion. Therefore, claims may be submitted for the reimbursement of the drug administration only.
Coverage and reimbursement of COVID-19-related treatments and procedures may vary from payer to payer; therefore, it is important that providers clarify and confirm any coding/billing requirements with respective payers.
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Packaging and Preparation
Isn’t it confusing to have two different vials? And the labels on the vials don’t say casirivimab or imdevimab?
Based on the rapid timing of the EUA and to meet the needs of the public health emergency, we are currently using the same vial sizes and labelling used as part of the clinical trial. We are working to update the labeling to reflect the new names (casirivimab and imdevimab) and are in ongoing discussions with the FDA on how it is best packaged.
When will the packaging with the drug name, ndc number, and color coding (version 3) become available in distribution?
We anticipate distribution of version 3 packaging when we have supplied the remainder of the stock of the version 1 and 2 packaging. We believe version 3 packaging will enter the distribution stream in the first quarter of 2021. There may be times where you receive shipments that include any combination of the three versions of the labeling.
There is no expiration dating on the package. What is the product expiration date?
As of Jan 2021, all distributed lots of REGEN-COV have an expiry date that is no earlier than 2022. The expiration date for the material shipped from the distributor can be found on the packing list. For the specific expiration dating for a lot please reach out to the distributor or to Regeneron medical information at 1-844-734-6643 or to [email protected]regeneron.com.
Does casirivimab or imdevimab packaging include latex?
The vial and vial stopper for casirivimab and imdevimab are not made with natural latex rubber.
Does the prepared IV bag need to be protected from light?
Prepared IV bags of casirivimab and imdevimab did not require protection from ambient light.
What are my options if I can’t start the IV infusion immediately?
If immediate administration is not possible, store the diluted REGEN-COV infusion solution in the refrigerator between 2°C to 8°C (36°F to 45°F) for no more than 36 hours or at room temperature up to 25°C (77°F) for no more than 4 hours. If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 30 minutes prior to administration.
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Clinical Data
How does REGEN-COV work?
The combination of casirivimab and imdevimab makes up REGEN-COV, Regeneron’s investigational anti-viral antibody cocktail being studied in COVID-19. It consists of two noncompeting, virus-neutralizing antibodies.
Casirivimab and imdevimab bind simultaneously to different, non-overlapping epitopes on severe acute respiratory syndrome 2 (SARS-CoV-2) Spike (S) glycoprotein.
Will REGEN-COV work across all variants of the virus?
REGEN-COV neutralizes and binds simultaneously to the spike protein receptor binding domain (RBD), which leads to decreased infectivity of host cells. Regeneron scientists evaluated thousands of fully-human antibodies produced by the company's VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies identified from humans who have recovered from COVID-19. The two virus neutralizing antibodies bind non-competitively to the critical receptor binding domain of the virus's spike protein.
Information about current variants can be found in our press release here.
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Safety Information and Reporting
What are my requirements for reporting medication errors and serious adverse events?
Prescribing healthcare professionals and/or the provider’s designee are responsible for mandatory reporting of all medication errors and all serious adverse events potentially related to REGEN-COV. These adverse events must be reported within 7 calendar days from the onset of the event. MedWatch adverse event reports can be submitted to the FDA online here, by using a postage-paid Form FDA 3500 and returning by mail/fax or by calling 1-800-FDA-1088 to request a reporting form. In addition, please provide a copy of all FDA MedWatch forms to Regeneron Pharmaceuticals, Inc via fax (1-888-876-2736) or email ([email protected]regeneron.com). See the Fact Sheet for Healthcare Providers for detailed information about the obligation to report medication errors and serious adverse events.
Are there any warnings associated with use of this combination therapy?
REGEN-COV is an unapproved investigational therapy, and there are limited clinical data available. Serious and unexpected adverse events may occur that have not been previously reported with REGEN-COV use.
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Warnings and Precautions
-
Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of REGEN-COV (casirivimab with imdevimab). If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care. Infusion-related reactions have been observed with administration of REGEN-COV. These reactions may be severe or life threatening.
- Signs and symptoms of infusion-related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrythmia (e.g., atrial fibrillation, tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness, fatigue and diaphoresis. If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care
- Clinical Worsening After REGEN-COV Administration: Clinical worsening of COVID-19 after administration of REGEN-COV has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to REGEN-COV use or were due to progression of COVID-19
- Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19: Benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients requiring high-flow oxygen or mechanical ventilation with COVID-19. Therefore, 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
-
Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of REGEN-COV (casirivimab with imdevimab). If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care. Infusion-related reactions have been observed with administration of REGEN-COV. These reactions may be severe or life threatening.
What adverse reactions have been identified thus far in the randomized trials?
The safety of REGEN-COV is based on analysis from one phase 1/2 trial of 799 ambulatory (non-hospitalized) patients with COVID-19.
- Serious adverse events (SAEs) were reported in 4 (1.6%) patients in the REGEN-COV 2,400-mg group, 2 (0.8%) patients in the REGEN-COV 8,000-mg group, and 6 (2.3%) patients in the placebo group. None of the SAEs were considered to be related to study drug. SAEs that were reported as Grade 3 or 4 adverse events were pneumonia, hyperglycemia, nausea and vomiting (2,400 mg REGEN-COV), intestinal obstruction and dyspnea (8,000 mg REGEN-COV) and COVID-19, pneumonia and hypoxia (placebo). REGEN-COV is not authorized at the 8,000-mg dose (4,000 mg casirivimab and 4,000 mg imdevimab)
- One anaphylactic reaction was reported in the clinical program. The event began within 1 hour of completion of the infusion, and required treatment including epinephrine. The event resolved. Infusion-related reactions, of Grade 2 or higher severity, were reported in 4 subjects (1.5%) in the 8,000-mg (4,000 mg casirivimab and 4,000 mg imdevimab) arm. These infusion-related reactions events were moderate in severity; and included pyrexia, chills, urticaria, pruritus, abdominal pain, and flushing. One infusion-related reaction (nausea) was reported in the placebo arm, and none were reported in the 2,400-mg (1,200 mg casirivimab and 1,200 mg imdevimab) arm. In two subjects receiving the 8,000-mg dose of REGEN-COV, the infusion-related reactions (urticaria, pruritus, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting) resulted in permanent discontinuation of the infusion. All events resolved.
Who is eligible for REGEN-COV under the EUA?
REGEN-COV (casirivimab with imdevimab to be administered together) is authorized for the treatment of mild to moderate coronavirus disease 2019 (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 at high risk for progressing to severe COVID-19 and/or hospitalization. [see Limitations of Authorized Use]
- REGEN-COV has not been approved, but has been authorized for emergency use by FDA
- This use is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner
- Healthcare providers should review the Fact Sheet for Healthcare Providers for information on the authorized use of REGEN-COV and mandatory requirements of the EUA and must comply with the requirements of the EUA. The FDA Letter of Authorization is available for reference, as well as the Dear Healthcare Provider Letter and Patient Fact Sheet
Limitations of Authorized Use
-
REGEN-COV (casirivimab with imdevimab) 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.
- Benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation.
Definition of High Risk Patients
High risk is defined as patients who meet at least one of the following criteria:
- Have a body mass index (BMI) ≥35
- Have chronic kidney disease
- Have diabetes
- Have immunosuppressive disease
- Are 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
-
Are 12 – 17 years of age AND have
- BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm, OR
- sickle cell disease, OR
- congenital or acquired heart disease, OR
- neurodevelopmental disorders (e.g. cerebral palsy), OR
- a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19), OR
- asthma, reactive airway or other chronic respiratory disease that requires daily medication for control
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Clinical Trials
How can I register my patients for a clinical trial with REGEN-COV for COVID-19?
For more information on clinical trials that are testing the use of REGEN-COV in COVID-19, please visit www.clinicaltrials.gov.
Is REGEN-COV being studied in ongoing clinical trials?
Please refer to the Clinical Trials page for more information. Clinical investigators, hospitals or clinical sites interested in joining the REGEN-COV clinical program can email Regeneron at [email protected]regeneron.com.
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Regeneron is working closely with health authorities and is focused on contributing our infectious disease expertise and resources to help patients and communities impacted by COVID-19.
IMPORTANT SAFETY INFORMATION
REGEN-COV (casirivimab with imdevimab) is an unapproved investigational therapy, and there are limited clinical data available. Serious and unexpected adverse events may occur that have not been previously reported with REGEN-COV use.
-
Warnings and Precautions
-
Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of REGEN-COV (casirivimab with imdevimab). If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care. Infusion-related reactions have been observed with administration of REGEN-COV. These reactions may be severe or life threatening.
- Signs and symptoms of infusion-related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrythmia (e.g., atrial fibrillation, tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness, fatigue and diaphoresis. If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care
- Clinical Worsening After REGEN-COV Administration: Clinical worsening of COVID-19 after administration of REGEN-COV has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to REGEN-COV use or were due to progression of COVID-19
- Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19: Benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients requiring high-flow oxygen or mechanical ventilation with COVID-19. Therefore, 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
-
Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of REGEN-COV (casirivimab with imdevimab). If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care. Infusion-related reactions have been observed with administration of REGEN-COV. These reactions may be severe or life threatening.
-
Adverse Reactions:
- Serious adverse events (SAEs) were reported in 4 (1.6%) patients in the REGEN-COV 2,400-mg group, 2 (0.8%) patients in the REGEN-COV 8,000-mg group, and 6 (2.3%) patients in the placebo group. None of the SAEs were considered to be related to study drug. SAEs that were reported as Grade 3 or 4 adverse events were pneumonia, hyperglycemia, nausea and vomiting (2,400 mg REGEN-COV), intestinal obstruction and dyspnea (8,000 mg REGEN-COV) and COVID-19, pneumonia and hypoxia (placebo). REGEN-COV is not authorized at the 8,000-mg dose (4,000 mg casirivimab and 4,000 mg imdevimab)
- One anaphylactic reaction was reported in the clinical program. The event began within 1 hour of completion of the infusion, and required treatment including epinephrine. The event resolved. Infusion-related reactions, of Grade 2 or higher severity, were reported in 4 subjects (1.5%) in the 8,000-mg (4,000 mg casirivimab and 4,000 mg imdevimab) arm. These infusion-related reactions events were moderate in severity; and included pyrexia, chills, urticaria, pruritus, abdominal pain, and flushing. One infusion-related reaction (nausea) was reported in the placebo arm, and none were reported in the 2,400-mg (1,200 mg casirivimab and 1,200 mg imdevimab) arm. In two subjects receiving the 8,000-mg dose of REGEN-COV, the infusion-related reactions (urticaria, pruritus, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting) resulted in permanent discontinuation of the infusion. All events resolved.
- Patient Monitoring Recommendations: Clinically monitor patients during infusion and observe patients for at least 1 hour after infusion is complete
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Use in Specific Populations:
- Pregnancy: There is currently limited clinical experience in the use of REGEN-COV in COVID-19 patients who are pregnant. REGEN-COV therapy should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus
- Nursing Mothers: There is currently no clinical experience in the use of REGEN-COV in COVID-19 patients who are breastfeeding. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for REGEN-COV and any potential adverse effects on the breastfed child from REGEN-COV or from the underlying maternal condition
AUTHORIZED USE
REGEN-COV (casirivimab with imdevimab to be administered together) is authorized for the treatment of mild to moderate coronavirus disease 2019 (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 progressing to severe COVID-19 and/or hospitalization. [see Limitations of Authorized Use]
- REGEN-COV has not been approved, but has been authorized for emergency use by FDA
- This use is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner
- Healthcare providers should review the Fact Sheet for Healthcare Providers for information on the authorized use of REGEN-COV and mandatory requirements of the EUA and must comply with the requirements of the EUA. The FDA Letter of Authorization is available for reference, as well as the Dear Healthcare Provider Letter and Patient Fact Sheet
Limitations of Authorized Use:
-
REGEN-COV (casirivimab with imdevimab) 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.
- Benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
Definition of High Risk Patients
High risk is defined as patients who meet at least one of the following criteria:
- Have a body mass index (BMI) ≥35
- Have chronic kidney disease
- Have diabetes
- Have immunosuppressive disease
- Are 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
-
Are 12–17 years of age AND have
- BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm, OR
- sickle cell disease, OR
- congenital or acquired heart disease, OR
- neurodevelopmental disorders (e.g. cerebral palsy), OR
- a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19), OR
- asthma, reactive airway or other chronic respiratory disease that requires daily medication for control
ADDITIONAL INFORMATION FOR HEALTHCARE PROVIDERS
- Casirivimab and imdevimab are each provided in a separate carton and vial. Casirivimab and imdevimab vial labels and carton labeling may instead be labeled REGN10933 and REGN10987, respectively.
- Each REGEN-COV dose pack contains sufficient number of vials of casirivimab (REGN10933) and imdevimab (REGN10987) to prepare one treatment dose.
- You may receive cartons and vials of casirivimab and imdevimab that are labeled "for intravenous infusion or subcutaneous injection." However, casirivimab and imdevimab must be administered together (although packaged separately) after dilution by intravenous (IV) infusion only
- Store casirivimab and imdevimab together in inventory. See www.regeneroneua.com/access for images of packaging
- REGEN-COV may only be administered in settings in which healthcare providers 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
- The recommended dose is 1200 mg of casirivimab with 1200 mg of imdevimab administered as a single intravenous infusion over at least 60 minutes as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 10 days of symptom onset. Since the optimal dosing regimen has not yet been established, it might be updated as data become available. See the Fact Sheet for Healthcare Providers for complete dosage, preparation, and administration instructions
- The prescribing healthcare provider and/or the provider's designee are responsible for mandatory reporting of all medication errors and ALL SERIOUS ADVERSE EVENTS potentially related to REGEN-COV. These adverse events must be reported within 7 calendar days from the onset of the event
- Healthcare facilities and providers must report therapeutics information and demonstrate adequate utilization via data reported through HHS Protect, Teletracking or National Healthcare Safety Network (NHSN) as directed by the U.S. Department of Health and Human Services
- MedWatch adverse event reports can be submitted to the FDA here, by using a postage-paid Form FDA 3500 and returning by mail/fax, or by calling 1-800-FDA-1088 to request a reporting form. In addition, please provide a copy of all FDA MedWatch forms to Regeneron Pharmaceuticals, Inc via fax (1-888-876-2736) or email ([email protected]regeneron.com)