Wisconsin DHS Health Alert #37: Important Changes to COVID-19 Monoclonal Antibody Ordering and Prescribing
Bureau of Communicable Diseases
December 22, 2021
Key Points
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Preliminary studies show that two commonly used monoclonal antibody treatments, casirivimab/indevimab (REGEN-COV®), and bamlanivimab/etesevimab, have reduced activity against the omicron variant of SARS-CoV-2, and may have little to no effectiveness in patients infected with the omicron variant.
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At this time, clinical use of casirivimab/indevimab and bamlanivimab/etesevimab is still recommended, although clinical guidance may evolve rapidly as omicron becomes increasingly prevalent. Sotrovimab, a monoclonal antibody treatment that appears to retain effectiveness against omicron, should be considered for treatment of eligible outpatients at the highest risk of severe disease, and who are suspected of having infection with the omicron variant.
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A new long-acting monoclonal antibody combination, tixagevimab co-packaged with cilgavimab (Evusheld™), has been granted emergency use authorization by the U.S. Food and Drug Administration for use as pre-exposure prophylaxis for patients at high risk of severe COVID-19. Criteria for authorized use, instructions related to storage and administration, and data reporting requirements are available through the published EUA and the fact sheet for healthcare providers.
- A limited supply of Evusheld has been allocated to DHS for delivery to Wisconsin. The initial allocation of 864 courses will be distributed to hospitals based on the regional population of each healthcare emergency readiness collation.
- In late November, the federal government paused shipment of sotrovimab to help ensure a more balanced portfolio of monoclonal antibody products. At this time sotrovimab is again available for ordering in Wisconsin, although the supply remains extremely limited.
Dear Colleagues,
The current surge of COVID-19 disease activity in the United States and the rapidly increasing incidence of the Omicron variant poses a challenge to our health care systems and risk of severe illness to patients across Wisconsin. Monoclonal antibody treatments have been a valuable tool for certain high risk patients and has known benefit for reducing the need for hospitalization. New research suggests that clinical recommendations around monoclonal antibodies may change rapidly in the coming days and weeks. This Health Alert contains information about what is currently known about the use of monoclonal antibodies and what may substantially change as the Omicron variant displaces Delta as the predominant strain circulating in Wisconsin.
Recommendation to reserve Sotrovimab for the highest risk patients.
In late November, prelimary research circulated on pre-print servers described findings showing that casirivimab/indevimab and bamlanivimab/etesevimab have limited or no activity against the Omicron variant. In response, the federal government paused shipment of the monoclonal antibody therapeutic sotrovimab in order to help ensure a more balanced portfolio of monoclonal antibody products and to allow more time to assess data regarding the effectiveness of sotrovimab against the Omicron variant.
Early in vitro data suggests sotrovimab retains activity against the Omicron variant. As such, allocation of sotrovimab to state and territorial health departments has resumed. The amount of sotrovimab allocated to states is determined using a methodology that takes into account COVID-19 incidence rates and hospitalizations.
The federal government’s current supply of sotrovimab is extremely limited, and additional doses of the product will not be available until the week of January 3rd. The federal government currently recommends that jurisdictions continue use of casirivimab/indevimab and bamlanivimab/etesevimab while reserving sotrovimab for treatment of eligible outpatients at highest risk who are either:
- Diagnosed with a test that may identify a potential case of the Omicron variant (e.g., by S gene Target Failure in the ThermoFisher TaqPath assay); or
- Are present in local settings where reported prevalence of Omicron is greater than 20%.
At the time of this writing, many areas of the United States have already passed the threshold where Omicron exceeds 20% of new COVID-19 cases. Providers should have awareness of rapidly changing guidance, and expect that casirivimab/indevimab and bamlanivimab/etesevimab may have no role at all in the near future.
Highest risk criteria for severe COVID-19 can be determined by local prioritization schemes, but criteria may include: age ≥65y, major immune suppression (e.g., recently diagnosed hematologic malignancy, cancer chemotherapy, solid organ transplant on immune suppression), obesity with BMI >35-40 kg/m2, cardiovascular disease (including hypertension), pregnancy, poorly controlled diabetes, significantly reduced kidney function, COPD, stroke, and two or more risk factors.
Health systems should take into consideration the NIH COVID-19 Treatment Guidelines Panel’s Statement on prioritization when there are logistical or supply constraints.
Availability of Evusheld, a new monoclonal antibody product for pre-exposure prophylaxis.
Evusheld is a new, unapproved combination of two monoclonal antibodies (tixagevimab co-packaged with cilgavimab) for pre-exposure prophylaxis of COVID-19 that was granted emergency use authorization (EUA) from the FDA on December 8, 2021. Tixagevimab and cilgavimab are neutralizing IgG1 monoclonal antibodies that bind to the receptor binding domain of the spike protein of the SARS-CoV-2 virus. Evusheld is administered as two separate consecutive intramuscular injections in an appropriately monitored, outpatient setting. Previously known as AZD7442, Evusheld has been shown to have preliminary evidence of safety and efficacy through an interim analysis of a randomized, placebo controlled Phase 3 trial (PROVENT Study). In this trial, the percentage of patients who had SARS-Cov-2 RT-PCR-positive symptomatic illness was 0.2% in the Evusheld group and 1.0% in the placebo group.
Patient Eligibility Criteria
Based on data submitted to FDA, Evusheld is authorized for use in adults and pediatric patients (12 years of age and older weighing at least 40 kg) who are not currently infected with SARS-CoV-2 and who have not had a recent exposure to an individual with COVID-19 and
- Who have moderate or severe immune compromise due to a medical conditions or receipt of immunosuppressive medications and may not mount a response to COVID-19 vaccination, or
- For whom vaccination with any approved COVID-19 vaccine is not recommend due a history of severe adverse reactions, such as anaphylaxis, to a COVID-19 vaccine or vaccine components.
The manufacturer has specified a list of medical conditions or treatments that may result in moderate to severe immune compromise and an inadequate immune response to COVID-19 vaccination. These conditions are listed in Table 1. Please note that other conditions, in addition to those listed below, may qualify a patient for Evusheld.
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Table 1. Medical conditions or treatments that may result in moderate to severe immune compromise
- Active treatment for solid tumor and hematologic malignancies
- Receipt of solid-organ transplant and taking immunosuppressive therapy
- Receipt of chimeric antigen receptor (CAR)-T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy)
- Moderate or severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome)
- Advanced or untreated HIV infection (people with HIV and CD4 cell counts <200/mm3, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV)
- Active treatment with high-dose corticosteroids (i.e., ≥20 mg prednisone or equivalent per day when administered for ≥2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor-necrosis (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory (e.g., B-cell depleting agents)
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Dosage
The dosage of EVUSHELD in adults and pediatric patients 12 years of age and older weighing at least 40 kg is 150 mg of tixagevimab and 150 mg of cilgavimab administered as two separate consecutive intramuscular injections. No dosage adjustment is recommended in pregnant or lactating individuals, in geriatrics, and in individuals with renal impairment. Full prescribing information is available for review through the manufacturers Provider Fact Sheet.
Other Instructions for Providers
Health care providers who prescribe Evusheld under the emergency use authorization are required to provide patients and/or their caregivers with information consistent with the conditions of authorization listed in the EUA, and provide a copy of the Fact Sheet for Patients, Parents and Caregivers.
Prescribing health care providers and/or their designee are responsible for mandatory reporting of all medication errors and serious adverse events potentially related to Evusheld treatment within 7 calendar days from the onset of the event. The reports should include unique identifiers and the words “Evusheld use for COVID-19 under Emergency Use Authorization (EUA)” in the description section of the report. Adverse event reports should be submitted to FDA MedWatch through the FDA online portal.
Due to the limited supply of Evusheld nationally, the number of patients meeting criteria for authorized use will exceed the number of available doses for the foreseeable future. Rationing decisions are therefore necessary at the federal, state, and health system level, to ensure that the drug is distributed in a way that is equitable and leads to maximum public health impact.
The federal government has allocated an initial supply of EVUSHELD to state health departments based on the population of each state. Wisconsin DHS is receiving 864 courses for its initial allocation. Each Healthcare Emergency Readiness Coalition (HERC) region in Wisconsin is receiving an allocation proportional to HERC population. For the initial distribution the largest eligible hospitals in each HERC Region will receive pre-determined quantity of Evusheld without ordering. An eligible hospital is one that indicated both willingness and capability to receive federal supplies of Evusheld as well as comply with all handling and reporting requirements. Eligible hospitals must be properly registered with the federal HPOP ordering system. This allocation mechanism was developed based on guidance from State Disaster Medical Advisory Committee (SDMAC) and is described in a document released January 2021. This framework discusses ethical issues that hospitals may consider when allocating this limited drug to patients, which can include involvement of a hospital ethics committee or “crisis triage team.”
Providers and pharmacists seeking guidance about individual patient treatment requests should not contact DHS but should instead discuss those situations within their health system. Administrators involved with ordering, shipping, and receiving drug from DHS may contact DHSOperations@dhs.wisconsin.gov with any questions.
Thank you for your collaboration.
Sincerely,
Ryan Westergaard, MD, PhD, MPH Chief Medical Officer and State Epidemiologist for Communicable Diseases
Wisconsin Department of Health Services
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