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EUA FACT SHEET HCP | PATIENT

FDA LETTER OF AUTHORIZATION

Casirivimab and Imdevimab

Authorized Use and Important Information for Healthcare Professionals

Casirivimab and imdevimab are investigational therapies and have been authorized by the FDA for the emergency use described below. Casirivimab and imdevimab must be administered together. Casirivimab and imdevimab are not FDA approved for any use. Safety and effectiveness of casirivimab and imdevimab have not yet been fully established for the treatment of COVID-19.

The Secretary of the Department of Health and Human Services has declared a public health emergency that justifies the emergency use of the unapproved products, casirivimab and imdevimab, to be administered together, 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 40kg) 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. In response, the US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for casirivimab and imdevimab, in the treatment of COVID-19.

Limitations of authorized use:

Casirivimab and imdevimab are 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 casirivimab and imdevimab 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 requiring high flow oxygen or mechanical ventilation with COVID-19.

  • 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.
  • Health care providers should review the Fact Sheet for Healthcare Providers for information on the authorized use of casirivimab and imdevimab and mandatory requirements of the EUA and must comply with the requirements of the EUA. The FDA Letter of Authorization is available here for reference, as well as the Dear Healthcare Provider Letter and Patient Fact Sheet.

Granted Emergency Use Authorization (EUA) by the FDA in the treatment of COVID-19

Casirivimab and imdevimab are investigational therapies and have been authorized by FDA for emergency use. Casirivimab and imdevimab must be administered together. Casirivimab and imdevimab are not FDA approved for any use. Safety and effectiveness of casirivimab and imdevimab have not been fully established for the treatment of COVID-19.

Casirivimab and imdevimab are authorized for use under an Emergency Use Authorization (EUA) 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 40kg) 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.

Casirivimab and imdevimab are 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 casirivimab and imdevimab 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 requiring high flow oxygen or mechanical ventilation with COVID-19.

High risk is defined as patients who meet at least one of the following criteria: Have a body mass index (BMI) ≥35, chronic kidney disease, diabetes, immunosuppressive disease [immunocompromised], 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 a 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 (e.g. cerebral palsy) or a medical-related technological dependence (e.g. 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.

Casirivimab and imdevimab neutralize and bind 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. In preclinical studies, each variant showing reduced susceptibility to one mAb retained susceptibility to the other, and all variants retained susceptibility to the casirivimab and imdevimab combination. The clinical impact of this is unknown and there is a potential risk of treatment failure due to the development of viral variants that are resistant to the casirivimab and imdevimab combination.

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.

EUA FACT SHEETS

Casirivimab and imdevimab are investigational therapies that have not yet been FDA-approved. The FDA has authorized distribution of these investigational therapies with Fact Sheets for health care providers, and patients and caregivers. These Fact Sheets, along with the FDA Letter of Authorization for EUA and Dear Healthcare Provider Letter to help prevent medication errors, are available below.

DOWNLOAD FACT SHEETS HERE:

FOR U.S. HEALTH CARE PROVIDERS (English)Download HCP Fact Sheet FOR PATIENTS AND CAREGIVERS (English)Download Patient Fact Sheet FOR PATIENTS AND CAREGIVERS (Spanish)Download Patient Fact Sheet FDA LETTER OF AUTHORIZATION FOR EUADownload FDA Letter of Authorization for EUA DEAR HEALTHCARE PROVIDER LETTERDownload Dear Healthcare Provider Letter

DOWNLOAD OUR GUIDEBOOK HERE:

Casirivimab and Imdevimab Emergency Use Authorization (EUA) GuidebookCasirivimab and Imdevimab Emergency Use Authorization (EUA) Guidebook

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

Casirivimab and imdevimab are unapproved investigational therapies and there are limited clinical data available. Serious and unexpected adverse events may occur that have not been previously reported with casirivimab and imdevimab use.

  • Warnings and Precautions
    • Hypersensitivity Reactions Including Anaphylaxis and Infusion-Related Reactions: There is a potential for serious hypersensitivity reaction, including anaphylaxis, with administration of casirivimab and 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 casirivimab and imdevimab. Signs and symptoms of infusion related reactions may include fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, and/or dizziness. If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care.
    • Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19: Benefit of treatment with casirivimab and imdevimab 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. Therefore, casirivimab and imdevimab are 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 casirivimab and imdevimab 2,400 mg group, 2 (0.8%) patients in casirivimab and imdevimab 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 casirivimab and imdevimab), intestinal obstruction and dyspnea (8,000 mg casirivimab and imdevimab) and COVID-19, pneumonia and hypoxia (placebo). Casirivimab and imdevimab are 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 include 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 casirivimab and imdevimab, 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 casirivimab and imdevimab in COVID-19 patients who are pregnant. Casirivimab and imdevimab 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 casirivimab and imdevimab 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 casirivimab and imdevimab and any potential adverse effects on the breastfed child from casirivimab and imdevimab or from the underlying maternal condition.

AUTHORIZED EMERGENCY USE

Casirivimab and imdevimab are investigational therapies authorized for use under an Emergency Use Authorization (EUA) 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.

Limitations of Authorized Use:

  • Casirivimab and imdevimab are 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 casirivimab and imdevimab 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 requiring high flow oxygen or mechanical ventilation with COVID-19.

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:
    • a 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 (e.g. cerebral palsy) or a medical-related technological dependence (e.g. 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 carton and vial labels may instead be labeled REGN10933 and REGN10987, respectively.
  • 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 infusion only.
  • Store casirivimab and imdevimab together in inventory. See www.Regeneroneua.com/access for images of packaging.
  • Casirivimab and imdevimab 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 and 1200 mg of imdevimab administered as a single intravenous infusion over at least 60 minutes as soon as possible after 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 new data becomes available. See the HCP Fact Sheet 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 casirivimab and imdevimab. 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 or email.

For Medical queries please contact [email protected] or 1-844-734-6643.

IMPORTANT SAFETY INFORMATION

Casirivimab and imdevimab are unapproved investigational therapies and there are limited clinical data available. Serious and unexpected adverse events may occur that have not been previously reported with casirivimab and imdevimab use.

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