FDA label 56e1175a-8d92-498a-9b96-b178f4d065fe

Treatment This EUA is for the use of the unapproved product, REGEN-COV (casirivimab and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied as individual vials to be administered together, for the treatment of mild to moderate COVID-19 in adult 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 (1.1) ] . Post-Exposure Prophylaxis This EUA is for the use of the unapproved product, REGEN-COV (casirivimab and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied as individual vials to be administered together, 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 Center 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) [see Limitations of Authorized Use (1.2) ] . Criteria for Identifying High Risk Individuals 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/m 2 , or if age 12-17, have BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm) 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, see the CDC website: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient. Available Dosage Forms of REGEN-COV: REGEN-COV (casirivimab and imdevimab) 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 together in a single carton (also referred to as a co-packaged carton), or in a dose pack. Routes of Administration for REGEN-COV: REGEN-COV may be administered by intravenous infusion or subcutaneous injection. FOR TREATMENT, 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. FOR POST-EXPOSURE PROPHYLAXIS, EITHER SUBCUTANEOUS INJECTION OR INTRAVENOUS INFUSION CAN BE USED. Treatment Dosage The authorized dosage is 600 mg of casirivimab and 600 mg of imdevimab administered together as a single intravenous infusion or by subcutaneous injection as soon as possible after positive SARS-CoV-2 viral testing and within 10 days of symptom onset [see Dosage and Administration (2.2) and Clinical Trial Results and Supporting Data for EUA (18.1) ] . The authorized dosage of 600 mg of casirivimab and 600 mg of imdevimab for subcutaneous administration for treatment is selected based on the totality of the scientific evidence, incorporating clinical data, viral load reduction data (pharmacodynamics) and pharmacokinetic data [see Clinical Pharmacology (14.2) and (14.3) ]. Post-exposure Prophylaxis Dosage The authorized dosage is 600 mg of casirivimab and 600 mg of imdevimab administered by subcutaneous injection or together as a single intravenous infusion as soon as possible following exposure to SARS-CoV-2. For individuals in whom repeat dosing is determined to be appropriate for ongoing exposure to SARS-CoV-2 for longer than 4 weeks and who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination, the initial dose is 600 mg of casirivimab and 600 mg of imdevimab by subcutaneous injection or intravenous infusion followed by subsequent repeat dosing of 300 mg of casirivimab and 300 mg of imdevimab by subcutaneous injection or intravenous infusion once every 4 weeks for the duration of ongoing exposure. The authorized dosage including dosage for repeat dosing is based on the totality of the scientific evidence including clinical pharmacology data and clinical trial data [see Clinical Trial Results and Supporting Data for EUA (18.2) and Clinical Pharmacology (14.3) ]. For Intravenous Infusion: Co-formulated casirivimab and imdevimab solution in a vial and casirivimab and imdevimab solutions in individual vials must be diluted prior to intravenous administration. Administer casirivimab and imdevimab together as a single intravenous infusion via pump or gravity (see Table 1 , Table 2 , Table 3 and Table 4 ). Clinically monitor patients during infusion and observe patients for at least 1 hour after infusion is complete. For Subcutaneous Injection: Administer casirivimab and imdevimab using the co-formulated solution in a vial or using the individual vials (see Table 5 and Table 6 ). Clinically monitor patients after injections and observe patients for at least 1 hour after injections. For treatment, subcutaneous injection is an alternative route of administration when intravenous administration is not feasible and would lead to delay in treatment. For post-exposure prophylaxis, either subcutaneous injection or intravenous infusion can be administered. REGEN-COV may only be administered in settings in which health care providers have immediate access to medications to treat a severe infusion or hypersensitivity reactions, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary. Health care providers must submit a report on ALL MEDICATION ERRORS and ALL SERIOUS ADVERSE EVENTS potentially related to REGEN-COV. See Sections 8 and 9 of the Full EUA Prescribing Information for reporting instructions below. Patients treated with REGEN-COV should continue to self-isolate and use infection control measures (e.g., wear mask, isolate, social distance, avoid sharing personal items, clean and disinfect "high touch" surfaces, and frequent handwashing) according to CDC guidelines. The authorized dosage may be updated as additional data from clinical trials becomes available. For information on clinical trials that are testing the use of REGEN-COV in COVID-19, please see www.clinicaltrials.gov.

Warnings There are limited clinical data available for REGEN-COV (casirivimab and imdevimab). Serious and unexpected adverse events may occur that have not been previously reported with REGEN-COV use. Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of REGEN-COV (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 therapy. 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, fatigue, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vasovagal reactions (e.g., pre-syncope, syncope), dizziness, and diaphoresis. Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of REGEN-COV under Emergency Use Authorization. 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 [see Limitations of Authorized Use (1.1) ] : 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.

5 WARNINGS AND PRECAUTIONS There are limited clinical data available for REGEN-COV (casirivimab and imdevimab). Serious and unexpected adverse events may occur that have not been previously reported with REGEN-COV use. 5.1 Hypersensitivity including Anaphylaxis and Infusion-Related Reactions Serious hypersensitivity reactions, including anaphylaxis, have been reported with administration of REGEN-COV (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, 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 [see Overall Safety Summary (6.1) ] . If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of REGEN-COV under Emergency Use Authorization. 5.2 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. 5.3 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 [see Limitations of Authorized Use (1.1) ] : 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.

6 OVERALL SAFETY SUMMARY 6.1 Clinical Trials Experience Overall, approximately 16,000 subjects have been exposed to REGEN-COV (casirivimab and imdevimab) in clinical trials in hospitalized and non-hospitalized subjects. Approximately 13,500 subjects received intravenous infusions and 2,500 subjects received subcutaneous injections. The safety of REGEN-COV (casirivimab and imdevimab) is based on analyses from COV-2067, a Phase 1/2/3 trial of ambulatory (non-hospitalized) subjects with COVID-19; COV-2069, a Phase 3 post-exposure prophylaxis trial for prevention of COVID-19; and COV-2093, a Phase 1 trial evaluating the safety and pharmacokinetics of REGEN-COV repeat subcutaneous dosing every 4 weeks for 24 weeks. COV-2067 This is a randomized, double-blind, placebo-controlled clinical trial in subjects with mild to moderate COVID-19 who had a sample collected for the first positive SARS-CoV-2 viral infection determination within 3 days prior to the start of the infusion. In the phase 3 portion of the trial, subjects were treated with a single intravenous infusion of 600 mg of casirivimab and 600 mg of imdevimab (n=827), or 1,200 mg of casirivimab and 1,200 mg of imdevimab (n=1,849), or 4,000 mg of casirivimab and 4,000 mg of imdevimab (n=1,012), or placebo (n=1,843). REGEN-COV is not authorized at the 4,000 mg of casirivimab and 4,000 mg of imdevimab dose. The 1,200 mg of casirivimab and 1,200 mg of imdevimab is no longer authorized under this EUA [see Clinical Trial Results and Supporting Data for EUA (18) ]. In pooled phase 1/2/3 analysis, 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 [see Warnings and Precautions (5.1) ]. 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 of casirivimab and 1,200 mg of imdevimab 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 [ see Warnings and Precautions (5.1) ]. 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 This is a randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of REGEN-COV (casirivimab and imdevimab) for post-exposure prophylaxis of COVID-19 in household contacts of individuals infected with SARS-CoV-2. Subjects who were SARS-CoV-2 negative at baseline were enrolled in Cohort A and received a single dose of 600 mg of casirivimab and 600 mg of imdevimab subcutaneously (n=1,311) or placebo (n=1,306). Adverse events were reported in 265 subjects (20%) in the REGEN-COV group and 379 subjects (29%) in the placebo group. 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. There were no cases of anaphylaxis. Subjects who were SARS-CoV-2 positive at baseline were enrolled in Cohort B and received a single dose of 600 mg of casirivimab and 600 mg of imdevimab subcutaneously (n=155) or placebo (n=156). Adverse events were reported in 52 subjects (34%) in the REGEN-COV group and 75 subjects (48%) in the placebo group. 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 REGN-COV group were ecchymosis and erythema. There were no cases of hypersensitivity reaction or anaphylaxis. COV-2093 This is a randomized double-blind, placebo-controlled Phase 1 trial evaluating the safety, pharmacokinetic and immunogenicity of repeated doses of 600 mg of casirivimab and 600 mg of imdevimab administered subcutaneously in healthy adult subjects. In COV-2093, subjects were randomized 3:1 to REGEN-COV (n=729) or placebo (n=240) administered every 4 weeks for 24 weeks. Adverse events were reported in 380 subjects (52%) in the REGEN-COV group and 111 subjects (46%) in the placebo group. Injection site reactions occurred in 12% and 4% of subjects following single dose administration in the REGEN-COV and placebo groups, respectively; the remaining safety findings following subcutaneous administration in the REGEN-COV group were similar to the safety findings observed with intravenous administration of REGEN-COV 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. The authorized dosage for repeat dosing for post-exposure prophylaxis of COVID-19 for certain individuals who remain at high risk of exposure for longer than 4 weeks is the initial dose of 600 mg casirivimab and 600 mg imdevimab followed by 300 mg of casirivimab and 300 mg of imdevimab administered every 4 weeks [see Dosage and Administration (2.2) ] .