Updated April 5, 2022
On April 5, the CDC estimated COVID-19 cases caused by the Omicron BA.2 variant is above 50% in all HHS regions. Effective immediately, sotrovimab will not be distributed to U.S. states and territories. The use of sotrovimab is not authorized at this time. The FDA Fact Sheet for sotrovimab reflects these use restrictions.
On March 25, the FDA announced that sotrovimab is no longer authorized for use in HHS regions 1 and 2 due to the high frequency of the Omicron BA.2 sub-variant. Data shows it's unlikely to be effective against this sub-variant. The regions impacted by this change include:
The FDA has issued a revised EUA for Evusheld (tixagevimab co-packaged with cilgavimab) to increase the initial dose for pre-exposure prophylaxis (prevention) of COVID-19 in certain adults and pediatric patients. This change is based on data indicating that Evusheld may be less active against certain Omicron subvariants. Evusheld should now be given as a 600 mg total dose of 300 mg of tixagevimab and 300 mg of cilgavimab. Read more on dosing changes.
Patients who have already received the previously authorized dose (150 mg of tixagevimab and 150 mg of cilgavimab) should receive an additional dose of 150 mg of tixagevimab and 150 mg of cilgavimab as soon as possible. Clinicians prescribing/offering Evusheld should notify their patients about the need for an additional dose.
Evusheld is authorized for the emergency use as pre-exposure prophylaxis (PrEP) for prevention of COVID-19 in certain adults and pediatric patients (12 years of age and older weighing at least 40 kg). Health care providers should only administer it to individuals who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to someone infected with SARS-CoV-2.
On Feb. 11, the FDA issued an EUA for bebtelovimab for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older) who are at high risk for progression to severe COVID-19. Bebtelovimab was observed to retain activity against both the omicron variant and the BA.2 omicron subvariant.
The AAFP's Getting Paid blog, CMS creates codes for newly authorized monoclonal antibody injections, outlines codes for administering bebtelovimab.
Early in vitro data suggests, that unlike the other antibody products, sotrovimab retains activity against the Omicron variant. Allocations of sotrovimab are limited and will be distributed this week to jurisdictions. More product will be available the first week of January.
In the interim, it is recommended that jurisdictions continue use of the bamlanivimab/etesevimab and casirivimab/imdevimab monoclonal antibody products for treating patients at highest risk for exposure to the Omicron variant. This would include individuals:
If the local prevalence of Omicron is less than 20%, jurisdictions are encouraged to direct sotrovimab to sites that can provide IV treatment (within 48 hours of collection of a patient sample) to highest risk, eligible individuals diagnosed with a test that may identify a potential case of the Omicron variant. Read more information.
Online Ordering for EUVASHELD Now Available: Jurisdictions and clinicians can place orders for tixagevimab/cilgavimab (EUVASHELD). Please note that there is a new portal for ordering any of the available products. Clinicians offering these treatments should have already gotten information/training from their jurisdictions.
On Dec. 8, the FDA issued an Emergency Use Authorization (EUA) for the use of the monoclonal antibody combination of tixagevimab and cilgavimab (EUVASHELD) for the pre-exposure prophylaxis of COVID-19 in immunocompromised individuals aged 12 and older. The EUA is specific for the following individuals:
IMPORTANT: EUVASHELD is not authorized for treatment of COVID-19 and is not a substitute for vaccination against COVID-19.
Clinical info: The product contains two vials of 150 mg of tixagevimab and cilgavimab which should be administered consecutively via intramuscular injection.
The EUA was based on 2 Phase III clinical trials that enrolled over 6,000 participants. Only one trial showed a reduction in symptomatic cases of COVID-19 (77%, 95% CI 46-90). There were cases of serious cardiovascular events, particularly myocardial infarction and heart failure, observed in the larger trial. Clinicians should inform patients about these increased risks prior to administration of the product.
On Dec. 3, the FDA amended the emergency use authorization for bamlanivimab and etesevimab to be administered together for the treatment of mild to moderate COVID-19 in all younger children, including newborns. Children must have a positive COVID-19 test and high risk for progression to severe COVID-19. This product is also authorized for post-exposure prophylaxis for prevention of COVID-19 in all children at high risk of progression to severe COVID-19, including hospitalization or death. Bamlanivimab/etesevimab is not for use in states, territories, and US jurisdictions in which the combined frequency of variants resistant to bamlanivimab and etesevimab exceeds 5%. See list.
This authorization was based on a clinical trial that included 125 pediatric patients (14 adolescent patients received placebo), all with at least one risk factor for severe COVID-19, to evaluate the safety and pharmacokinetics of treatment in pediatric patients. The authorized dosage for younger individuals weighing less than 40 kg will vary depending on weight.
More information can be found in the clinician handout.
On July 30, the FDA expanded the EUA for the COVID-19 monoclonal antibody therapeutic REGEN-COV (casirivimab and imdevimab) to include post-exposure prophylaxis, which includes known exposure without a positive test. Post-exposure prophylaxis is authorized for adults and adolescents 12 years of age and older who are:
Eligible individuals must have either been exposed to an individual infected with SARS-CoV-2 (e.g. close contact per CDC) or at high risk of exposure due to COVID-19 infections in other individuals in the same setting (e.g. long term care facilities and correctional facilities).
Casirivimab plus imdevimab may be administered as either subcutaneous injection or a single IV infusion. Refer to the updated updated Fact Sheets for full details about dosing and administration. Combatcovid.org can help you ensure rapid access to monoclonal antibody treatment for your high-risk COVID-19 patients. Use their toolkit and support resources for administering the antibodies.
This new authorized use is in addition to the prior authorization of REGEN-COV to treat non-hospitalized patients with mild to moderate COVID-19 in adult and pediatric patients, aged 12 and older, 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.
NOTE: Post-exposure prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19, and REGEN-COV is not authorized for pre-exposure prophylaxis. Full vaccination combined with use of masks and other mitigation strategies are the best way to end the pandemic.
Additional information on monoclonal antibody treatments can be found in the clinician handouts from FDA:
All treatments are neutralizing IgG1 monoclonal antibodies that bind to the receptor binding domain of the spike protein of SARS-CoV-2.They are investigational drugs and not currently approved for any indication. The data supporting the EUA for casirivimab/imdevimab was based on an interim analysis from a phase two randomized, double-blind, placebo-controlled clinical trial in non-hospitalized adults with mild to moderate COVID-19 symptoms. The EUAs for sotrovimab and the combined treatment with bamlanivimab/etesevimab were based on phase III clinical trial data showing a reduction in hospitalizations in patients with mild to moderate COVID-19 symptoms.
All treatments have been authorized for use by clinicians in an outpatient setting to treat mild to moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing who are 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 (e.g. body mass index (BMI) ≥35, chronic kidney disease, diabetes, immunosuppressed, over 65 years of age). The antibody treatments will need to be mixed and transfused at health care facilities with this capability. The treatments are most effective early in the course of infection so they will need to be prescribed and dispensed within 10 days of symptom onset.
NOTE: bamlanivimab alone is not effective against the newer variants of SARS-CoV-2. The FDA has revoked its emergency use authorization for bamlanivimab alone. Read more. The combined treatment options of bamlanivimab/etesevimab and casirvimab/imdevimab are still available and authorized for use. Sotrovimab is another option that is available commercially under the conditions of the EUA.
The NIH treatment guidelines recommend use of bamlanivimab plus etesevimab, casirivimab plus imdevimab, or sotrovimab, for the treatment of outpatients with mild to moderate COVID-19 who are at high risk of clinical progression as defined by the EUA criteria. New information: the FDA has authorized changes in the doses for casirivimab plus imdevimab from 2400 mg to 1200 mg (600 mg casirivimab and 600 mg imdevimab). None of the treatments are authorized for use in patients who are hospitalized or experience anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary.
Additional resources from HHS and ASPR include an allocation dashboard, distribution playbook, and information for clinicians.
The treatment will be available with no out-of-pocket costs for patients. CPT codes will be issued for reimbursement of clinicians administering the infusion. CMS has released billing and payment guidance for Medicare beneficiaries.