Let’s Prevent Hospitalizations and Consider Monoclonal Antibody Treatments
In November, 2020, FDA issued Emergency Use Authorizations (EUA) for two monoclonal antibody products. An EUA is different than full FDA approval in that it is issued in emergent circumstances, usually without the comprehensive studies required for full licensure of the product. Because of this limited data, concerns have been reasonably raised about use of these products.
One product is produced by Regeneron and is composed of two antibodies (Casirivimab and Imdevimab) and the other by Eli Lilly (Bamlanivimab). The Lilly product was studied in a limited number of non-hospitalized COVID positive patients with higher risk for COVID progression, and when compared to similar patients receiving placebo, hospitalizations were reduced. This data is publicly available, but again, a small sample size suggests the need for further studies before FDA can issue full approval. There is no definitive public study data available on the Regeneron product.
In both cases the product is identified for use in COVID positive patients, less than 10 days from onset of symptoms, who meet criteria that focus on pre-existing risk factors such as BMI>35, COPD, diabetes, etc. (see the JAMA article cited below for details). The anticipated outcome is to prevent hospitalization for these patients at very high risk for adverse COVID related outcomes. For a variety of reasons (discussed briefly below) these products have not been widely employed despite the surge in hospitalizations forcing many hospitals to invoke crisis standards of care and rationing of services. Perhaps we should consider wider use.
The concerns about use have a sound basis. A December 17, 2020, blog in Health Affairs (see below) raises most of the issues cogently and the considerations need attention if effective and appropriate use of these products is to be advanced:
- Lack of substantive data and the need for further randomized controlled studies (RCT) – Indeed, those studies are required to fully support efficacy and safety for full licensure, but the EUA allows for use in specific cases to prevent hospitalization. The circumstances for use must consider gathering data that would complement RCTs. This can be managed.
- Logistics of distribution and administration of the products – Thus far it has been distributed to hospitals who may not be configured to administer the antibodies in an outpatient setting. There are hospitals who have however instituted such an outpatient service with the triage and injection capability to address the use appropriately with documentation and follow up to assess outcomes. The administration of these products requires patient monitoring for up to three hours post-injection and this presents a staffing and space challenge. But again, these issues can be well managed with an effective operational plan.
- Equity of access to the antibodies – This too must and can be addressed. Several injection clinics for these products have been implemented with clear attention to underserved populations who have been most affected by COVID. Collaborations with public health and community advocacy entities can assist in identifying locations for injection clinics and expand messaging and outreach to help these populations recognize and exploit the potential preventive benefits. It is clear that equity of access must be a major consideration in planning and implementing a program.
- Financial concerns - Access to these products must be supported through public insurance (Medicare and Medicaid) where appropriate. Private insurance funding should also be made available to ensure that the injections’ funding does not present a barrier.
If these concerns are addressed in the operating plan, effective use of these tools may reduce pressure on over-burdened hospitals. The data to date shows that 15% of people treated with Lilly’s product did not require hospital care. While this is not a large number it can make a difference. With appropriate and responsible execution, we can make a difference.
1. An EUA for Bamlanivimab – A Monoclonal Antibody for Covid-19; JAMA published online December 11, 2020
2. Emergency Use Authorization for Covid 19 Monoclonal Antibodies: Challenges and Lessons Learned; C. DeJong, B. Lo, A. Chen; Health Affairs Blog; December 17, 2020