FACT SHEET UPDATE:
On 9/9/21, the fact sheet for healthcare providers was updated. As of 9/9/21, the fact sheet for healthcare providers has been updated. Click to view information on the addition of co-packaged cartons of individual vials of casirivimab and imdevimab and the addition of 5% Dextrose as a diluent when administering REGEN-COV via IV infusion. See the latest fact sheet for healthcare providers for more information.

(Effective September 9, 2021) Changes include but are not limited to:

Dosage and Administration (Box, Section 2.4, Section 3, Section 19): addition of co-packaged carton of individual vials of casirivimab and imdevimab

Dosage and Administration (Section 2.4): addition of 5% Dextrose as diluent

Doctor looking at lab results Doctor looking at lab results

Secondary Endpoints

TREATMENT OF MILD TO MODERATE COVID-19 (COV-2067)

A STATISTICALLY SIGNIFICANT, 29% REDUCTION IN TIME TO COVID-19 SYMPTOM RESOLUTION

In a Phase 3 trial (COV-2067) conducted over 29 days in over 4,000 subjects with a positive SARS-CoV-2 RT-qPCR result from nasopharyngeal (NP) swab at randomization and with at least one factor for severe coronavirus disease 2019 (COVID-19), i.e. the modified full analysis set (mFAS):

Key Secondary Endpoint: Median Time to COVID-19 Symptom Resolution (Days) (COV-2067)

REGEN-COV
600 mg of casirivimab and 600 mg of imdevimab (intravenous)

Median days to symptom resolution

10

Median reduction (days)

4
(P=0.0001)

Placebo

Median days to symptom resolution

14

Median reduction (days)

4
(P=0.0001)

REGEN-COV
600 mg of casirivimab and 600 mg of imdevimab (intravenous)
Placebo
Median days to symptom resolution 10 14
Median reduction (days) 4
(P=0.0001)

Symptoms assessed were fever, chills, sore throat, cough, shortness of breath/difficulty breathing, nausea, vomiting, diarrhea, headache, red/watery eyes, body aches, loss of taste/smell, fatigue, loss of appetite, confusion, dizziness, pressure/tight chest, chest pain, stomachache, rash, sneezing, sputum/phlegm, runny nose. Time to COVID-19 symptom resolution was defined as time from randomization to the first day during which the subject scored ‘no symptom’ (score of 0) on all of the above symptoms except cough, fatigue, and headache, which could have been ‘mild/moderate symptom’ (score of 1) or ‘no symptom’ (score of 0).

TREATMENT OF MILD TO MODERATE COVID-19 (COV-2067)

STATISTICALLY SIGNIFICANT REDUCTIONS IN VIRAL LOAD

REDUCTIONS IN LS MEAN VIRAL LOAD WITH REGEN-COV THROUGH DAY 15 VS PLACEBO

Treatment with REGEN-COV resulted in a statistically significant reduction in the LS mean viral load (log10 copies/mL) from baseline to Day 7 compared to placebo (-0.71 log10 copies/mL for 600 mg dose of casirivimab and 600 mg of imdevimab and -0.86 log10 copies/mL for 2,400 mg; p<0.0001). Reductions were observed in the overall mFAS population and in other subgroups, including those with baseline viral load >106 copies/mL or who were seronegative at baseline. Consistent effects were observed for the individual doses, indicating the absence of a dose effect. The graph below shows the mean change from baseline in SARS-CoV-2 viral load to Day 15.

Change from Baseline in SARS-CoV-2 Viral Load
(log10 copies/mL) to Day 15 (COV-2067)

Secondary Endpoint: Change from Baseline in SARS-CoV-2 Viral Load

Study design and demographics: In the Phase 3 (COV-2067) portion of the trial, 4,567 subjects with at least one risk factor for severe COVID-19 were randomized to a single intravenous infusion of 600 mg of casirivimab and 600 mg of imdevimab (n=838), 1,200 mg of casirivimab and 1,200 mg of imdevimab (n=1,529), 4,000 mg of casirivimab and 4,000 mg of imdevimab (n=700), or placebo (n=1,500) groups. The two REGEN-COV doses at the start of Phase 3 were 4,000 mg and 1,200 mg of each component; however, based on Phase 1/2 efficacy analyses showing that the 4,000 mg and 1,200 mg doses of each component were similar, the Phase 3 portion of the protocol was amended to compare the 1,200 mg dose of each component vs. placebo and the 600 mg dose of each component vs. placebo. Comparisons were between subjects randomized to the specific REGEN-COV dose and subjects who were concurrently randomized to placebo.

At baseline, in all randomized subjects with at least one risk factor, the median age was 50 years (with 13% of subjects ages 65 years or older), 52% of the subjects were female, 84% were White, 36% were Hispanic or Latino, and 5% were Black or African American. In subjects with available baseline symptom data, 15% had mild symptoms, 42% had moderate symptoms, 42% had severe symptoms, and 2% reported no symptoms at baseline; the median duration of symptoms was 3 days; mean viral load was 6.2 log10 copies/mL at baseline. The baseline demographics and disease characteristics were well balanced across the casirivimab and imdevimab and placebo treatment groups.

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.

IMPORTANT SAFETY INFORMATION

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

  • Contraindication:
    REGEN-COV is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to REGEN-COV
  • 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: 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
    • Post-exposure prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19
  • Adverse Reactions:
    • COV-2067 (Treatment): 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. 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
    • COV-2069 (Post-exposure prophylaxis): In subjects who were SARS-CoV-2 negative at baseline (Cohort A), injection site reactions (all grade 1 and 2) occurred in 55 subjects (4%) in the REGEN-COV group and 19 subjects (2%) in the placebo group. The most common signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the REGEN-COV group were erythema and pruritus. Hypersensitivity reactions occurred in 2 subjects (0.2%) in the REGEN-COV group and all hypersensitivity reactions were grade 1 in severity. In subjects who were SARS-CoV-2 positive at baseline (Cohort B), injection site reactions, all of which were grade 1 or 2, occurred in 6 subjects (4%) in the REGEN-COV group and 1 subject (1%) in the placebo group. The most common signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the REGEN-COV group were ecchymosis and erythema
    • COV-2093 (Subcutaneous Dosing): Injection site reactions occurred in 12% and 4% of subjects following single dose administration in the REGEN-COV and placebo groups, respectively. Remaining safety finding following subcutaneous administration in the REGEN-COV group were similar to the safety findings observed with intravenous administration in COV-2067. With repeat dosing, injection site reactions occurred in 252 subjects (35%) in the REGEN-COV group and 38 subjects (16%) in the placebo group; all injection site reactions were grade 1 or 2 in severity. Hypersensitivity reactions occurred in 8 subjects (1%) in the REGEN-COV group; and all hypersensitivity reactions were grade 1 or 2 in severity. There were no cases of anaphylaxis.
  • Patient Monitoring Recommendations: Clinically monitor patients during dose administration 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
AUTHORIZED USE

Treatment:

REGEN-COV 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.

Limitations of Authorized Use (Treatment)

  • 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
  • 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

Post-Exposure Prophylaxis:

REGEN-COV is authorized in adult and pediatric individuals (12 years of age and older weighing at least 40 kg) for post-exposure prophylaxis of COVID-19 in individuals who are at high risk for progression to severe COVID-19, including hospitalization or death, and are:

  • not fully vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination (for example, individuals with immunocompromising conditions including those taking immunosuppressive medications) and
    • have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per Centers for Disease Control and Prevention (CDC), or
    • who are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (for example, nursing homes, prisons)

Limitations of Authorized Use (Post-Exposure Prophylaxis)

  • 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

REGEN-COV has not been approved, but has been authorized for emergency use by FDA

These uses are 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 uses 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

Criteria for Identifying High Risk Individuals

Please refer to the Fact Sheet for Healthcare Providers for criteria for identifying high risk individuals.

SARS-CoV-2 Viral Variants

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.

Reporting Adverse Events

  • 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])

*Individuals are considered to be fully vaccinated 2 weeks after their second vaccine dose in a 2-dose series (such as the Pfizer or Moderna vaccines), or 2 weeks after a single-dose vaccine (such as Johnson & Johnson’s Janssen vaccine). See this website for more details: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html#vaccinated

See this website for more details: https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated-people.html

Close contact with an infected individual is defined as: being within 6 feet for a total of 15 minutes or more, providing care at home to someone who is sick, having direct physical contact with the person (hugging or kissing, for example), sharing eating or drinking utensils, or being exposed to respiratory droplets from an infected person (sneezing or coughing, for example). See this website for additional details: https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/quarantine.html

IMPORTANT SAFETY INFORMATION

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

  • Contraindication:
    REGEN-COV is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to REGEN-COV
  • 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: 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
    • Post-exposure prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19
  • Adverse Reactions:
    • COV-2067 (Treatment): 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. 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
    • COV-2069 (Post-exposure prophylaxis): In subjects who were SARS-CoV-2 negative at baseline (Cohort A), injection site reactions (all grade 1 and 2) occurred in 55 subjects (4%) in the REGEN-COV group and 19 subjects (2%) in the placebo group. The most common signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the REGEN-COV group were erythema and pruritus. Hypersensitivity reactions occurred in 2 subjects (0.2%) in the REGEN-COV group and all hypersensitivity reactions were grade 1 in severity. In subjects who were SARS-CoV-2 positive at baseline (Cohort B), injection site reactions, all of which were grade 1 or 2, occurred in 6 subjects (4%) in the REGEN-COV group and 1 subject (1%) in the placebo group. The most common signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the REGEN-COV group were ecchymosis and erythema
    • COV-2093 (Subcutaneous Dosing): Injection site reactions occurred in 12% and 4% of subjects following single dose administration in the REGEN-COV and placebo groups, respectively. Remaining safety finding following subcutaneous administration in the REGEN-COV group were similar to the safety findings observed with intravenous administration in COV-2067. With repeat dosing, injection site reactions occurred in 252 subjects (35%) in the REGEN-COV group and 38 subjects (16%) in the placebo group; all injection site reactions were grade 1 or 2 in severity. Hypersensitivity reactions occurred in 8 subjects (1%) in the REGEN-COV group; and all hypersensitivity reactions were grade 1 or 2 in severity. There were no cases of anaphylaxis.
  • Patient Monitoring Recommendations: Clinically monitor patients during dose administration 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

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