Important Packaging Information

The development and manufacturing of casirivimab and imdevimab has been funded in part with federal funds from the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services (HHS) under OT number: HHSO100201700020C.

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 (eg, 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 (eg, 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
• 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
• 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
  • Lactation: 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

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, OR
  • sickle cell disease, OR
  • congenital or acquired heart disease, OR
  • neurodevelopmental disorders, for example, 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

Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies. Healthcare providers should review the Antiviral Resistance information in Section 15 of the Fact Sheet for Healthcare Providers for details regarding specific variants and resistance, and refer to the CDC website as well as information from state and local health authorities regarding reports of viral variants of importance in their region to guide treatment decisions.

• 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 regencov.com/hcp/dosing/packaging 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 authorized dosage is 1200 mg of casirivimab with 1200 mg of imdevimab administered together as a single intravenous (IV) infusion as soon as possible after a positive viral test for SARS-CoV-2 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])

1. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html