Pharmacists Navigate the Unprecedented EUA Jungle

mAbs, Infusion Therapy & Flow Regulators

 

While working diligently with federal and local government and health departments to bring the brilliant COVID-19 vaccines to the masses, pharmacists are simultaneously navigating the challenges of providing access to several new drugs that have received FDA emergency use authorization (EUA) in the treatment of COVID-19 infection.

“There have been twelve FDA EUAs for therapeutics used in the prevention and treatment of COVID-19 and related serious conditions in the past several months, more than the total drugs receiving FDA EUA that most pharmacists can recall in their entire career.”

Historical FDA EUAs include an anthrax vaccine in 2005 for military personnel and Tamiflu in 2009 for infant use in the H1N1 pandemic, but few clinicians have experience navigating the FDA EUA jungle that has become reality this past year. Scientific evidence of the benefit of many of these FDA EUA therapies in the fight against COVID-19 is mounting and the U.S. government has purchased billions of dollars of some of these drugs, leaving pharmacists to complete the arduous and complicated work of safely bringing these brand new medications to the patients that need them.

In addition to the three COVID-19 vaccines and Remdesivir, now FDA approved, there are four Monoclonal AntiBody therapies, referred to as “mAbs,” that have received FDA EUA for the outpatient treatment of mild to moderate COVID-19 in patients (12 years or older) at high risk for severe disease or hospitalization. Studies indicate that these medications, when given early in the course of the SARS-CoV-2 infection can prevent progression to severe disease, hospitalization, and death. Bamlanivimab was the first to receive FDA EUA on November 9th, 2020. Shortly after on November 21, 2020, REGEN-CoV (Casirivimab and Imdevimab) followed. This year, on February 9th the combination, Bamlanivimab and Etesevimab, joined the mAb COVID-19 treatment armament.

mAbs used in COVID-19 are engineered versions of antibodies that are naturally produced by the immune system in response to an invasion of the SARS-CoV-2 virus. U.S. TV watchers that were paying attention to the generic drug names in those direct-to-consumer drug company advertisements noticed many other mAb drugs currently FDA approved or treatment in various other diseases including Crohn’s disease, asthma, arthritis, plaque psoriasis, and cancer. mAbs are Immunomodulators, “biologic” medications used to modify or regulate immune functions, designed with very specific biochemical or cellular targets. The SARS-CoV-2 specific MAbs target part of the infamous spike protein of the virus, preventing it from entering human cells and inhibiting viral replication. Studies indicate these COVID-19 specific antibody drugs can help protect high-risk patients from ending up in the hospital or dying from COVID-19. These therapies are intended for outpatient treatment of eligible high-risk patients with mild to moderate symptoms and positive direct SARS-CoV-2 test in the last 10 days. Eligible high-risk patients include those 65 years of age or older and also patients 12 years of age and older with diseases and conditions that increase their risk of severe disease and hospitalization from COVID-19. Visit combatcovid.hhs.gov to learn more about Monoclonal Antibody Therapies in COVID-19, your eligibility, and how to access them.

 

The U.S. Government has agreed to purchase billions of dollars of these four COVID-19 mAbs and more than 2.8 million doses are committed by the end of this month. Just this past February, Eli Lilly announced an agreement with the U.S. Government for the purchase of a minimum of 100,000 doses of the bamlanivimab and etesevimab combination therapy for $210m delivered through March 31, 2021. The U.S. Government has already agreed to purchase 1,450,000 doses of bamlanivimab alone from Eli Lilly and 1 million doses have already been delivered with the remaining doses expected by March 31, 2021. In December, the powerhouse drug maker announced a purchase agreement with the U.S. Government for $812.5 million for 650,000 of those bamlanivimab doses. In January 2021, the U.S. Government also agreed to purchase 1.25 million doses of the combination Casirivimab and Imdevimab from Regeneron for $2.6 billion.

While healthcare facilities may charge a fee for the administration of the therapies, ultimately these government purchases are intended to allow eligible patients to receive these therapies at no out-of-pocket cost. The allocation and distribution of these therapies are coordinated by the U.S. Department of Health and Human Services and the Office of the Assistant Secretary for Preparedness and Response (HHS/ASPR). PHE offers resources for infusion centers, healthcare providers, and patients on their website. In addition to the state-based allocation of these outpatient therapies, federal allocations are being directed to priority settings caring for high-risk patients, like long-term care facilities and home infusion pharmacies, through The Special Projects for Equitable and Efficient Distribution (SPEED) program.

As the government allocates and distributes these therapies to the states and healthcare settings caring for our most vulnerable patients, pharmacists are reviewing the rapidly evolving clinical information, and are using their expertise to help ensure safe administration of these therapies to patients. Managing the drug preparation and administration challenges of these therapies includes complex considerations. These therapies require intravenous (IV) infusion and clinical monitoring of patients during the infusion and for at least 1 hour after completion of the infusion to assess for infusion-related reactions. Each drug has specific preparation, storage, and administration instructions. Depending on the mAb used, the time to complete the infusion process can take 15 minutes up to 3 hours or more. Additionally, these therapies can be infused using cost-effective gravity infusion with Flow Regulators containing 0.2-micron low protein binding in-line filters (PMIFR300) or can be infused using infusion pumps.

New information released from the drug manufacturers has improved the feasibility and practicality of administering these drugs including smaller volume and shorter infusion duration than originally directed. These medications are not FDA approved and there are limitations to their benefit and potential risk of use in hospitalized patients with severe COVID-19 that are on a ventilator or requiring high flow oxygen. For outpatient use, the FDA EUAs for these COVID-19 mAbs include specific patient eligibility criteria (non-hospitalized patients at high risk for progressing to severe disease or hospitalization) and should be given within 10 days of symptom onset. These are manageable points to navigate for pharmacists that work miracles every day in patient care, most now happily trudging through the EUA jungle, proudly providing the proper pronunciations, reviewing clinical studies, and remaining the steady medication experts, relieved to see the beginning of the end of COVID-19.