FDA Authorizes Revisions to Fact Sheets for Casirivimab and Imdevimab Monoclonal Antibodies for Treatment of COVID-19 to Include a Change in Dose and Option for Subcutaneous Administration
On June 3, 2021, the U.S. Food and Drug Administration (FDA) authorized revisions to the Emergency Use Authorization (EUA) for use of REGEN-COV (casirivimab and imdevimab) 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. These revisions include a change in dosing of REGEN-COV from 2400 mg (1200 mg casirivimab and 1200 mg imdevimab) to 1200 mg (600 mg casirivimab and 600 mg imdevimab), and the addition of a new presentation consisting of a single vial containing casirivimab and imdevimab co-formulated in a 1:1 ratio for either intravenous infusion or subcutaneous injection.
There are two different formulations of REGEN-COV: 1) casirivimab and imdevimab co-formulated solution containing two antibodies in a 1:1 ratio in a vial, and 2) casirivimab and imdevimab available as individual antibody solutions in separate vials, which may be supplied in separate cartons or in a dose pack. There are differences in the way the two formulations are prepared. Intravenous infusion is strongly recommended for both formulations. Subcutaneous injection is an alternative route of administration when intravenous infusion is not feasible and would lead to delay in treatment. Carefully follow the preparation procedures in the Fact Sheet for Health Care Providers linked below.
REGEN-COV is not authorized for use in patients who are hospitalized due to COVID-19, 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 REGEN-COV has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies (mAbs), 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. Additional information regarding Limitations of Authorized Use and Warnings and Precautions can be found in the Fact Sheet for Health Care Providers linked below.
Efficacy and Rationale for EUA Revisions
Based on review of the analysis of Phase 3 data from a Phase 1/2/3 randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of a single intravenous infusion of 600 mg casirivimab and 600 mg imdevimab in outpatients (non-hospitalized) with SARS-CoV-2 infection, it is reasonable to believe that REGEN-COV may be effective for the treatment of mild to moderate 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, and that, when used under the conditions described in this authorization, the known and potential benefits of REGEN-COV outweigh the known and potential risks of such product.
Additional Information
The updated Fact Sheet for Health Care Providers provides essential information about using REGEN-COV administered together in treating COVID-19 as authorized and is available at https://go.usa.gov/xsUJb. An updated fact sheet for patients, parents, and caregivers is available at https://go.usa.gov/xsUJ5 and contains information for understanding the potential risks and potential benefits of taking REGEN-COV, including side effects.
The EUA authority allows FDA to help strengthen the nation’s public health protections against chemical, biological, radiological, and nuclear threats by facilitating the availability and use of medical countermeasures needed during public health emergencies. The issuance of an EUA is different than an FDA approval. In determining whether to issue an EUA, the FDA evaluates the totality of available scientific evidence and carefully balances any known or potential risks with any known or potential benefits of the product for use during an emergency. For additional information on the EUA authority and EUAs for COVID-19, please visit https://go.usa.gov/xs8x4.
To promote public confidence in FDA’s scientific review process and in ultimately appropriately using products authorized for emergency use, FDA’s Center for Drug Evaluation and Research (CDER) recently launched a new webpage to facilitate access to information from CDER’s scientific review documents supporting EUAs for drug and biological therapeutic products that the Agency has disclosed. This webpage compiles the scientific review documents supporting EUAs for COVID-19 drug and biological therapeutic products that the Agency has disclosed into one location to make documents easier to find and can be accessed at https://go.usa.gov/xsHzW.
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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.