The Federal COVID Response (FCR) Therapeutics Team, under the U.S. Department of Health & Human Services (HHS), provides resources to support rapid access to monoclonal antibody (mAb) treatment for high-risk patients with COVID-19. Early intervention with mAb treatment may reduce the risk of severe illness and hospitalization for people with COVID-19 who are at high risk of developing more serious illness, and clinical pharmacists can help by identifying patients who may benefit and starting them on treatment in a timely process. Recently, the FDA revised the emergency use authorization (EUA) for REGEN-COV (casirivimab and imdevimab, administered together), authorizing REGEN-COV for emergency use as postexposure prophylaxis for COVID-19 in adults and pediatric individuals (12 years and older weighing at least 40 kg) at high risk of progression to severe COVID-19, including hospitalization or death. Research is also under way with current and new mAb treatments on emerging variants of the virus.
On July 22, ACCP hosted a discussion with representatives from the FCR Therapeutics Team and the HHS Office of the Assistant Secretary for Preparedness and Response, providing an opportunity for ACCP members to ask questions about mAb treatments ranging from clinical and operational considerations to equitable access. In addition to answering questions from ACCP members during the 30-minute discussion, the FCR team answered previously submitted questions from members that were not asked live because of time restraints. Below are the FCR team’s responses to ACCP member inquiries.
The window for mAb treatment is within 10 days of symptom onset, but we know earlier is better. What is the ideal timing of administration for maximum benefit?
Although we cannot speak to that level of specificity, it is imperative that, once symptoms have been identified and a positive test has been confirmed, treatment begin as quickly as possible to achieve maximum outcome and occur within the timeline as indicated in the FDA EUA.
How can we increase access to these medications and inform patients about getting these therapies sooner?
We are attempting to work with multiple patient advocacy groups, particularly those in underserved communities, not only to inform them that these treatments exist but also to address misinformation about them. We encourage clinical pharmacists to do the same at the local level. Patients can also contact the Combat COVID Monoclonal Antibodies Call Center at (877) 332-6585 or visit the following websites for information:
What role might mAbs play in the inpatient setting? Should we be using them in patients determined to benefit who may be in the hospital for another reason but found to have COVID?
Monoclonal antibody therapeutics should be used in patients who meet the FDA EUA eligibility (there is a provision that allows health care professionals to use their clinical judgment). Monoclonals are intended for those experiencing mild to moderate COVID symptoms. Monoclonals, according to the FDA EUA, are NOT intended for those hospitalized because of severe COVID illness, those who require oxygen because of COVID, or those who require an increase in baseline oxygen flow rate because of COVID-19 or those on chronic oxygen therapy because of underlying non–COVID-19–related comorbidities.
Should the subcutaneous preparations of the REGEN-COV product be encouraged for use in the ambulatory/primary care setting?
According to the current EUA for the treatment of mild to moderate COVID-19 infection, “Intravenous infusion is strongly recommended. Subcutaneous injection is an alternative route of administration when intravenous infusion is not feasible and would lead to a delay in treatment.”
What would need to be done to prepare subcutaneous injections of the REGEN-COV product in the clinic setting?
For the administration of the 600 mg of casirivimab and 600 mg of imdevimab:
- Gather the four syringes and prepare for subcutaneous injection (each syringe will be 2.5 mL).
- Administer the subcutaneous injection consecutively and each at a different injection site, into the thigh, back of the upper arm, or abdomen except 2 inches around the naval. The waistline should be avoided.
- When administering the subcutaneous injections, it is recommended that providers use different quadrants of the abdomen or upper thighs or back of the upper arms to space apart each 2.5-mL subcutaneous injection. DO NOT inject into skin that is bruised, scarred, tender, or in any way damaged.
- Clinically monitor patients after these injections and observe patients for 1 hour.
How do we treat patients who received one dose of vaccine but contracted COVID and received an mAb before the second dose?
Patients treated for COVID-19 with mAbs or convalescent plasma should wait 90 days before getting a COVID-19 vaccine, according to CDC guidance. Monoclonal antibodies can be detected for up to 90 days. There is a possibility that the mAb treatments could attack or work against the vaccine.
What role do these COVID-19 treatment options play in health equity, and what role should health equity play in prescribing these treatments?
We at HHS are attempting to contact organizations that serve primarily underserved populations to help raise the awareness of these therapies and get these therapies to as many people as possible who would benefit from them. We are not aware of studies currently available that are looking specifically at this outreach and the results of this work, but it is a good thought.
If patients have previously received mAb treatment for a COVID-19 infection, can they receive treatment again if they contract the virus again?
That has not yet been studied.
Can patients receive a second dose if they fail to respond to the initial dose? What about switching agents in an attempt to have increased efficacy or gain efficacy against a new variant?
The EUAs currently issued allow for one-time dosing for COVID-19 infection. There are no data on potential interactions between monoclonals, patient reactions, etc. Because the monoclonals are not 100% effective, some patients will progress to more severe illness.
Related to the language within the current EUA handouts as well as updates to the available dosing/indication for the casirivimab/imdevimab therapy:
- In section 2.1, Patient Selection, of the clinician handout for the EUA mAbs, after the specific inclusion criteria are listed, the statement that “other medical conditions or factors may also place individual patients at high risk for progression to severe COVID-19 and authorization of [monoclonal antibody] under the EUA is not limited to the medical conditions or factors listed above” is mentioned. Does this statement imply that providers can still recommend mAb administration to patients designated by that provider as having risk factors for severe disease even if those risk factors are not listed specifically in the EUA?
High-risk conditions are outlined in the EUA; however, clinician discretion is allowed if patients have a condition not listed in the EUA that the clinician believes places them at risk of progressing to severe disease. In this instance, the patient would be eligible for monoclonal therapy.
Has there been any discussion concerning the pre-print data from the RECOVERY Collaborative Group on using high-dose casirivimab/imdevimab (4 g/4 g instead of 600 mg/600 mg) IVPB for admitted seronegative patients with COVID-19?
We can only speak to the information in the EUA.
Why is bamlanivimab still available?
Bamlanivimab/etesevimab is on pause because of its efficacy against specific variants. The EUA was not revoked because bamlanivimab/etesevimab is effective against other variants, and appropriate use of monoclonals is continuously evaluated by the CDC, the FDA, and other partners.
ACCP members can view the recording of the 30-minute session and access the presentation slides here. ACCP encourages its members to share this information to further public health efforts in improving COVID-19 infection outcomes. To contribute to preventive measures and increasing vaccination rates, clinical pharmacists are encouraged to access the messaging resources from its partners at the This Is Our Shot coalition.