Casirivimab/imdevimab is an investigational monoclonal antibody cocktail that has been engineered to bind to and neutralize SARS-CoV-2 and prevent progression to severe illness.
Clinical trial data in outpatients have shown that casirivimab/imdevimab may reduce viral load and/or COVID-19 medically attended visits.[1] [2]
Clinical trial data in hospitalized patients, however, have not shown a benefit with casirivimab/imdevimab use in patients requiring high-flow oxygen or mechanical ventilation, and it is not authorized for use in patients who are hospitalized due to COVID-19. [3]
The U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) on November 21, 2020 for the use of casirivimab/imdevimab for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age or older weighing at least 40 kilograms [about 88 pounds]) who test positive for SARS-CoV-2 and who are at high risk for progressing to severe COVID-19.
In March 2021, the FDA released a revised fact sheet for health care providers, which now include additional information on in vitro susceptibility of SARS-CoV2 variants to each of the monoclonal antibody therapies. The revised Fact Sheet for Health Care Providers, which includes this data as well as the full conditions of use, should be reviewed prior to administration of the medication. [4]
In May 2021, the FDA issued updates to the EUA. Updates included expanded high-risk criteria for patient selection.
EUA conditions of use include the following:
Treatment should be initiated as soon as possible after a positive viral test for SARS-CoV2 (either antigen or molecular PCR test) and within 10 days of symptom onset. CDPH recommends initiating treatment as soon as the positive results have been obtained, as early treatment is expected to have the most benefit.
High-risk criteria include older age, being overweight/obese, pregnancy, chronic kidney disease, diabetes, immunosuppression, cardiovascular disease or hypertension, chronic lung diseases, sickle cell disease, neurodevelopmental disorders, having a medical-related technological dependence, or other medical conditions or factors (for example, race or ethnicity) that may also place individual patients at high risk for progression to severe COVID-19. Authorization for use of monoclonal antibody treatment is not limited to the medical conditions or factors listed above. Healthcare providers should consider the benefit-risk for an individual patient. For more information, please see the Fact Sheet for Health Care Providers.
Casirivimab/imdevimab is not authorized for use in patients who are hospitalized due to COVID-19 or who require oxygen therapy due to COVID-19. Treatment is also not authorized for asymptomatic patients. Casirivimab/imdevimab is indicated for patients with mild or moderate symptoms, including fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, or shortness of breath with exertion.
Casirivimab/imdevimab may only be administered in settings in which health care providers have immediate access to medications to treat a severe infusion reaction, such as anaphylaxis.
Patients are clinically monitored during treatment and observed for at least 60 minutes after infusion. There is the potential for serious hypersensitivity reactions, including anaphylaxis, with casirivimab/imdevimab administration (see full EUA prescribing information in the Fact Sheet for Health Care Providers).
Health care providers are responsible for mandatory FDA MedWatch reporting of all medication errors and serious adverse events or deaths considered to be potentially attributable to casirivimab/imdevimab.
Health care providers must communicate information consistent with the Fact Sheet for Patients, Parents and Caregivers and provide a copy prior to the patient receiving casirivimab/imdevimab.[5]
The NIH COVID-19 Treatment Guidelines Panel as of April 8, 2021 recommends using casirivimab plus imdevimab to treat outpatients with mild to moderate COVID-19 who are at high risk of clinical progression, as defined by the EUA criteria (AIIa).
The Panel also states the following:
Treatment should be started as soon as possible after the patient receives a positive result on a SARS-CoV-2 antigen or nucleic acid amplification test (NAAT) and within 10 days of symptom onset.
The Panel recommends against the use of anti-SARS-CoV-2 monoclonal antibodies for patients who are hospitalized because of COVID-19, except in a clinical trial (AIIa). However, their use should be considered for persons with mild to moderate COVID-19 who are hospitalized for a reason other than COVID-19 but who otherwise meet the EUA criteria.
The Infectious Diseases Society of America (IDSA) Guideline Panel as of April 11, 2021 recommends the use of casirivimab/imdevimab rather than no neutralizing antibodies among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease (conditional recommendation, low certainty of evidence).
The Panel also states the following:
Patients with mild to moderate COVID-19 who are at high risk of progression to severe disease admitted to the hospital for reasons other than COVID-19 may also receive casirivimab/imdevimab.
Local variant susceptibility may be considered in the choice of the most appropriate neutralizing antibody therapy.
There are limited data on efficacy of casirivimab/imdevimab in high-risk patients between 12 and 18 years of age.
Acquiring casirivimab/imdevimab for EUA use:
All treatment sites must now order casirivimab plus imdevimab directly from AmerisourceBergen Corporation (ABC). The products remain free of charge to requesting sites. Treatment sites should review the direct ordering process guide and place orders directly with ABC at this site.
Should you have any questions or concerns regarding the direct order process for COVID-19 monoclonal antibodies, you may contact Health and Human Services' (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR) at COVID19Therapeutics@hhs.gov or ABC at C19therapies@amerisourcebergen.com.
In addition to direct ordering, California Department of Public Health has a large inventory of casirivimab/imdevimab that are available via standard Medical/Health Resource Request in Sales Force. Contact your local county Medical and Health Operational Area Coordinator (MHOAC) for more information.
To provide options for monoclonal antibody treatment beyond acute care hospitals, the federal government has encouraged utilization of these products in non-hospital settings like skilled nursing facilities (SNFs), federally qualified health centers (FQHCs), urgent care centers, and correctional facilities.
For facilities and healthcare providers interested in setting up infusions for high-risk patients with COVID-19, ASPR has many resources available. This includes free digital content that your facility can use on social media platforms to help educate providers and patients. HHS has also provided the Combat Covid webpage as a resource for your patients.
For more information for providers and facilities regarding monoclonal antibody infusions, please visit COVID Therapeutics Webpage Monoclonal Info for Providers. [6]
Weinreich, David M, et al. "REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19: NEJM." New England Journal of Medicine, 21 Jan. 2021, www.nejm.org/doi/10.1056/NEJMoa2035002.
Phase 3 Trial Shows REGEN-COV™ (casirivimab with imdevimab) Antibody Cocktail Reduced Hospitalization or Death by 70% in Non-hospitalized COVID-19 Patients | Regeneron Pharmaceuticals Inc.
Regeneron Press Release. REGN-COV2 Independent Data Monitoring Committee Recommends Holding Enrollment in Hospitalized Patients with High Oxygen Requirements and Continuing Enrollment in Patients with Low or No Oxygen Requirements. October 30, 2020. Available at: https://investor.regeneron.com/news-releases/news-release-details/regn-cov2-independent-data-monitoring-committee-recommends
Casirivimab and Imdevimab EUA Fact Sheet for Healthcare Providers (fda.gov)
Fact Sheet for Patients, Parents, and Caregivers: Emergency Use Authorization (EUA) of casirivimab and imdevimab for COVID-19 (fda.gov)
COVID Therapeutics Webpage – Monoclonal Info for Providers
Originally published on Decemeber 31, 2020