Casirivimab and Imdevimab (REGEN-COV)

KEY POINTS

• Casirivimab (REGN10933) and imdevimab (REGN10987) are recombinant human IgG1 monoclonal antibodies that target the receptor binding domain of the spike protein of SARS-CoV-2, which can reduce viral replication
  • Monoclonal antibodies are molecules engineered to serve as substitute antibodies that can restore, enhance or mimic the immune system’s attack on cells
  • Is a form of passive immunity
  • The ending of the name “vi” is for targeting viruses and “mab” stands for monoclonal antibody
• Casirivimab and imdevimab are given together, neither is FDA-approved for any indication either alone or in combination
• This medication is produced by Regeneron Pharmaceuticals and was given to U.S. President Donald Trump when he had COVID-19
  • It may reduce the need for hospitalization or emergency department visit when given in accordance with EUA criteria to patients with SARS-CoV-2 variants for which it has activity. Clinical data are provided in the Fact Sheet.
• Was given Emergency Use Authorization (EUA) status from the FDA on 22 November 2020, this FDA EUA was later revoked on January 26th 2022 due to lack of activity against the Omicron variant as the predominant variant in circulation
  • EUA covered use by healthcare providers in an outpatient settings to treat mild to moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing who were 12 years of age and older weighing at least 40 kg, and who are at high risk for progressing to severe COVID-19 and/or hospitalization
    • There is a long, broad list of criteria for what is considered “high risk”
    • Use in “outpatient” infusion sites is challenging from an infection control standpoint and overall logistics standpoint
    • Use later in disease may lead to worse outcomes, is recommended to give within 10 days of symptom onset, however was approved in the UK for use in patients hospitalized with COVID-19
  • Was approved for use as post-exposure prophylaxis versus SARS-CoV-2
  • Was not authorized in the USA to be given to:
    • Adults or pediatric patients who are hospitalized due to COVID-19
    • Adults or pediatric patients who require oxygen therapy due to COVID-19
    • Adults or pediatric patients who require an increase in baseline oxygen flow rate due to COVID-19 in those patients on chronic oxygen therapy due to underlying non-COVID-19-related comorbidity
• Dosage was 600 mg of casirivimab and 600 mg of imdevimab (1,200 mg total) administered together either (1) subcutaneous as 4 separate 2.5 mL injections or (2) as a single infusion diluted in 0.9% NS given over at least 60 minutes via pump or gravity
  • Was initially approved as 1200mg/1200mg (2400mg total dose) to be given IV only
  • Infusion or injection should be followed by a 1 hour observation period to monitor for adverse drug reactions
  • No dose adjustment for renal function, effect of hepatic dysfunction is unknown
• Casirivimab and imdevimab came in multiple formulations
  • Unopened vials required storage under refrigeration
• Adverse events:
  • Infusion-related reactions (fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness)
  • Anaphylaxis and allergic reactions, one was reported to occur in the trial
    • Began within 1 hour of completing the infusion and required treatment with epinephrine
  • Adverse events reported as Grade 3 or 4 in the clinical trial with these drugs were pneumonia, hyperglycemia, nausea and vomiting (2,400 mg casirivimab and imdevimab), intestinal obstruction and dyspnea (8,000 mg casirivimab and imdevimab)
• Adverse reactions were to be reported to FDA Medwatch & Regeneron Pharmaceuticals
• Patient must have been provided with the “Fact Sheet for Patients, Parents and Caregivers” and be agreeable to the therapy
• Drug-drug interactions are suspected to be unlikely