The last year and a half brought many rapid changes and innovations across the globe and in no area more than healthcare. From finding the most effective treatments to developing tests and vaccines, altering our history, and creating an environment focused on both innovation and speed. Healthcare workers and scientists led the way in creating new treatments and prevention protocols in response to the COVID-19 pandemic. However, despite all the advances, we only have one FDA-approved treatment for COVID-19 and the weight of the pandemic continues to pressure test our healthcare system.
In order to facilitate the need for immediate solutions, the Food and Drug Administration (FDA) has utilized Emergency Use Authorizations (EUAs) which allows for the use of unapproved medical products in urgent settings when there are no adequate approved alternative therapies available, such as in a global pandemic.
A total of eleven therapies have been granted for EUA by the FDA since 2020 for use in fighting the COVID-19 epidemic. These therapies cover a range of use cases and have been created to manage other areas outside of the infection, such as providing continuous renal replacement therapy (CRRT) or sedation for infected patients. Several other new therapies have been developed and are continually analyzed for effectiveness in treating COVID-19. In addition, we have seen some therapies that are FDA-approved for other disease states, now being tested for efficacy in coronavirus settings. Continued innovation, testing and data analysis for therapies to treat patients with COVID-19 are needed to increase survival and decrease hospitalizations. This article will share a summary of the existing therapies currently being used to treat Covid-19.
Current Covid-19 Treatments
Veklury (remdesivir) is an antiviral that was initially given an EUA and then received full approval by the FDA in October 2020. Veklury was approved for use in patients 12 years of age or older and weighing at least 40 kilograms (kg) for the treatment of COVID-19 requiring hospitalization. Veklury has been issued another EUA for the treatment of suspected or laboratory confirmed COVID-19 in hospitalized pediatric patients weighing 3.5kg to less than 40kg or hospitalized patients less than 12 years of age weighing at least 3.5kg.
Monoclonal antibodies are lab-synthesized copies of antibodies which can enhance or mimic our immune system’s response to fight off infection. Monoclonal antibodies are being investigated to treat mild to moderate COVID-19 infected patients that are at least 12 years of age and weigh at least 40kg that are at high risk for progressing to severe COVID-19 and/or hospitalization. The FDA defines high risk as age 65 or older, having a Body Mass Index (BMI) of greater than 25kg/m^2, pregnancy, chronic kidney disease, diabetes, immunosuppressive disease or treatment, cardiovascular disease, chronic lung disease, sickle cell disease, neurodevelopmental disorders and medical-related technological dependence.
Based on results from animal studies, monoclonal antibodies may reduce the viral load in the airways of infected animals. The FDA granted EUAs to GlaxoSmithKline’s sotrovimab, Lilly’s (bamlanivimab/etesevimab), and Regeneron’s REGEN-COV (casirivimab/imdevimab). Monoclonal antibody treatment is to be started on a patient as soon as the diagnosis of COVID-19 is confirmed and within the first seven days of initial symptoms.
Lilly’s (bamlanivimab/etesevimab) was suspended in June 2021 for use within the United States based on concerns for potential resistance of the COVID variants to this therapy.
GlaxoSmithKline’s sotrovimab is given as a single 500 milligram (mg) intravenous (IV) dose. In an unpublished study of 500 patients, sotrovimab showed a decrease in the rate of hospitalization and death compared to placebo at day 29.
Regeneron’s REGEN-COV (casirivimab/imdevimab) is given as a single 600mg-600mg IV dose and is also available to be administered subcutaneously (subcut) if the person is unable to tolerate the IV route. REGEN-COV (casirivimab/imdevimab) was studied in a phase 3 trial of 4,000 adult non-hospitalized patients with mild to moderate COVID-19 and who were at risk for progression to severe disease. The drug combination was given to patients within seven days of initial symptom onset and demonstrated a reduction in hospitalization and death at day 29.
Sotrovimab and REGEN-COV have both shown to retain neutralizing activity against the variants and are the only monoclonal antibodies the FDA has recommended for use at this time. It appears there’s ample supply of REGEN-COV with no cost share to members. It’s uncertain when these biologics will get full FDA approval, possibly at the end of this year or beginning of 2022, but once fully approved we’re not sure if the US government will continue to purchase and distribute these biologics.
High-titer convalescent plasma
High-titer convalescent plasma also has an EUA for COVID-19 treatment of hospitalized patients. Convalescent plasma is a product that is derived from patients that have recovered from a COVID-19 infection. The study enrolled about 500 patients and was compared to placebo. While the treatment was found to be safe, it was not found to be efficacious for patients with mild to moderate COVID-19 that were admitted into the emergency department. Convalescent plasma is still being studied to understand in which settings this treatment may be most useful.
FDA Approved Drugs Used to Treat RA
There are two already FDA-approved drugs that are now being further evaluated for their role in COVID-19 treatment: Actemra (tocilizumab) and Olumiant (baricitinib). These agents differ in mechanism of action but are both used to treat Rheumatoid Arthritis.
Tocilizumab is an Interleukin (IL)-6 inhibitor which works to decrease inflammatory cytokines. It has been found that elevated inflammatory markers and cytokines have been associated with severe COVID-19. Therefore, it is hypothesized that blocking the inflammatory pathway may help prevent disease progression. The National Institute of Health (NIH) and the Infectious Diseases Society of America (IDSA) recommend the use of tocilizumab with glucocorticoids in hospitalized patients as standard care, for those on high-flow oxygen and that have been admitted into the intensive care unit (ICU) within the last 24 hours or have significantly elevated inflammatory markers. Overall, data suggests a mortality benefit with tocilizumab when compared to placebo for infected patients (28% tocilizumab versus 33% placebo).
Baricitinib, a Janus Kinase (JAK) inhibitor, is being considered for its potential antiviral effects in COVID-19 infected patients. The EUA issued for baricitinib requires it to be used in combination with remdesivir in COVID-19 patients that require oxygen support. However, there is also data to support baricitinib’s use alone, as supported by the NIH’s recommendations. In an unpublished trial, when added to standard of care, baricitinib reduced the 28-day mortality rate compared to placebo (17.5% baricitinib and 29.4% placebo) for patients on high-flow oxygen or non-invasive ventilation at baseline. Most of the patients in this study were already receiving glucocorticoids and about 20% were receiving remdesivir.
Although data is promising for both hospitalized and outpatient COVID-19 patients, further research is required to understand the survival rates, the adverse effect profiles and other safety concerns with the investigational agents for COVID-19 treatments. It is our responsibility as healthcare workers and payers to be diligent in reviewing the latest data regarding treatments and their use within the EUA requirements to provide the best care to all patients.