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 and 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. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive therapy. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of REGEN-COV under EUA. Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, 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, arrhythmia (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, vasovagal reactions (e.g., pre-syncope, syncope), dizziness, fatigue and diaphoresis. Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs
  • 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, arrhythmia (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 with COVID-19 requiring high-flow oxygen or mechanical ventilation. 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:
  • In a pooled phase 1/2/3 analysis of COV-2067, infusion-related reactions (adverse event assessed as causally related by the investigator) of grade 2 or higher severity have been observed in 10/4,206 (0.2%) of those who received REGEN-COV at the authorized dose or a higher dose
  • Overall, in Phase 1/2/3, three subjects receiving the 8,000 mg dose of REGEN-COV, and one subject receiving the 1,200 mg casirivimab and 1,200 mg imdevimab, had infusion-related reactions (urticaria, pruritus, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, rash) which resulted in permanent discontinuation of the infusion. All events resolved
  • Anaphylactic reactions have been reported in the clinical program in subjects receiving REGEN-COV. The events began within 1 hour of completion of the infusion, and in at least one case required treatment including epinephrine. The events resolved
  • The safety with subcutaneous administration is based on analysis from HV-2093, a randomized double-blind, placebo-controlled trial evaluating the safety and pharmacokinetic profile in healthy volunteer adult subjects. Subjects were randomized 3:1 to REGEN-COV (n=729) or placebo (n=240). Injection site reactions were observed in 12% and 4% of subjects following single dose administration in the casirivimab and imdevimab, and placebo arms respectively; the remaining safety findings with subcutaneous administration in the casirivimab and imdevimab arm were similar to the safety findings observed with intravenous administration in COV-2067
• Patient Monitoring Recommendations: Clinically monitor patients during infusion and observe patients for at least 1 hour after intravenous infusion or subcutaneous dosing is complete
• Use in Specific Populations:
  • Pregnancy: There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. REGEN-COV should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus
  • Lactation: There are no available data on the presence of casirivimab and/or imdevimab in human milk or animal milk, the effects on the breastfed infant, or the effects of the drug on milk production. 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 and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied as individual vials 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 progression to severe COVID-19, including hospitalization or death. [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 and 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

The following medical conditions or other factors may place adults and pediatric patients (age 12-17 years and weighing at least 40 kg) at higher risk for progression to severe COVID-19:

• Older age (for example, age ≥65 years of age)
• Obesity or being overweight (for example, BMI >25 kg/m², or if age 12-17, have BMI ≥85th percentile for their age and gender based on CDC growth charts)
• Pregnancy
• Chronic kidney disease
• Diabetes
• Immunosuppressive disease or immunosuppressive treatment
• Cardiovascular disease (including congenital heart disease) or hypertension
• Chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension)
• Sickle cell disease
• Neurodevelopmental disorders (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
• Having a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19))

Other medical conditions or factors (for example, race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19 and authorization of REGEN-COV under the EUA is not limited to the medical conditions or factors listed above.

For additional information on medical conditions and factors associated with increased risk for progression to severe COVID-19, see the CDC website. Healthcare providers should consider the benefit-risk for an individual patient.

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 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.

• REGEN-COV is available as:
  1. A single vial which contains two antibodies co-formulated in a 1:1 ratio of casirivimab and imdevimab or
  2. Individual antibody solutions in separate vials, which may be supplied in separate cartons or in a dose pack
• Each REGEN-COV dose pack contains sufficient number of vials of casirivimab (REGN10933) and imdevimab (REGN10987) to prepare up to two treatment doses (600 mg of casirivimab and 600 mg of imdevimab)
• REGEN-COV may be administered by IV infusion or subcutaneous injection. Intravenous infusion is strongly recommended. Subcutaneous injection is an alternative route of administration when intravenous infusion is not feasible and would lead to delay in treatment
• 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 600 mg of casirivimab with 600 mg of imdevimab administered together as a single intravenous (IV) infusion or by subcutaneous injection 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 submitting 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.covid19treatmentguidelines.nih.gov/

1. https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

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

1. COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines. National Institutes of Health.

https://www.covid19treatmentguidelines.nih.gov/. Accessed May 25th, 2021.