UVA Health shares that the Regeneron monoclonal antibody cocktail known as Casirivimab and Imdevimab (REGN10933 and REGN1098) were able to block 100% of the symptomatic COVID-19 infections participating in a clinical trial here. According to one of the site’s investigators, those trial participants that actually developed any asymptomatic infections accumulated materially less virus than the norm—leading to a shortening of infection duration time based on interim data recently shared by Regeneron. According to Dr. William Petri Jr., “This is the first treatment shown to prevent COVID-19 after a known exposure, and offers protection for unvaccinated individuals caring for a family member with COVID-19.” The UVA COVID-19 clinic, led by Dr. Debbie-Anne Shirly, expressed thanks to the nurses and staff in this important study, noting, “Their day-to-day support made our participation in this trial possible.”
Promising Results of Protection as ‘Passive Vaccine’
TrialSite chronicled the genesis of this monoclonal antibody with great interest. With the pandemic raging, the New York State-based sponsor initiated a series of clinical trials to investigate efficacy and safety. Regeneron was able to secure $450 million from BARDA for at-risk development and manufacturing for this sophisticated “cocktail” combining SARS-CoV-2 antibodies from A) proprietary technology enabling humanized mice and B) convalescent plasma. The original early safety study included some unorthodox features, including a sentinel cohort to serve as a safety signal for the overseeing Independent Data Monitoring Committee (IDMC). The company, however, was pleasantly transparent sharing information on request.
The company recently announced positive results from one of their ongoing Phase 3 clinical trials evaluating the combined investigational product for use as a “passive vaccine” for the prevention of SARS-CoV-2 for people facing high risk of infection due to household contacts. The clinical trial is run jointly with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
Most recently, the company shared in a press release the results of exploratory analysis involving the first approximately 400 evaluable individuals participating in the study. After receiving the passive vaccination (1,200 mg via subcutaneous injections) or placebo, the company reported that A) passive vaccination with REGN-COV) results in 100% prevention of symptomatic infection (8/223 placebo vs. 0/186 REGN-COV) and approximately 50% lower overall rates of infection (symptomatic and asymptomatic) (23/223 placebo vs. 10/186 REGN-COV); and B) The lower number of infections occurring with REGN-COV2 therapy were all asymptomatic, marked by decreasing peak virus levels and condensed duration of viral shedding. Of note, those infections that were observed in the placebo group on average were marked by 100-fold higher peak viral load. Those infections in the REGN-COV group lasted no more than a week while approximately 40% of the infections in the placebo group lasted 3-4 weeks. Additional observations can be read in the full press release.
The placebo group incurred more adverse events than the study drug cohort—18% vs. 12% respectively. Regeneron suggested there were infections in the placebo group. One COVID-19 related death and hospitalization did occur in the placebo group—none in the study drug group. This antibody cocktail isn’t a vaccine and won’t provide permanent immunity to SARS-CoV-2, reports local news media Rappahannock News.
NIH Guidelines & EUA Status
The NIH shares via its COVID-19 Treatment Guidelines that the cocktail product, “two recombinant human monoclonal antibodies that bind to nonoverlapping epitopes of the spike protein receptor-binding domain (RBD)” of SARS-CoV-2, serve to prevent the binding of the RBD to the human host cell. By November 21, 2020, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) making Casirivimab plus imdevimab available for treatment of non-hospitalized patients with mild to moderate COVID-19 who face high risk for progression of disease and/or hospitalization. A reminder—an EUA is not a product approval. It is still considered investigational.
The REGN-COV Household Contacts Program
As TrialSite has chronicled, a number of studies are ongoing involving this study drug targeting SARS-CoV-2. The “Household Contacts” study (NCT04452318) evaluates the Regeneron monoclonal antibody compound in four (4) cohorts, including 1) (Cohort A) adults and adolescents 12 and above who are SARS-CoV-2 negative at baseline; 2) (Cohort A1) pediatric subjects 12 an under who are SARS-CoV-2 negative at baseline; 3) (Cohort B) adult and adolescent participants 12 and up who are SARS-CoV-2 positive at baseline; and 4) (Cohort B1) pediatric subjects 12 and under who are SARS-CoV-2 positive at baseline.
Targeting a total of 2,450 participants initially, the Phase 3 trial runs till this Summer and is heavily supported by NIAID and its COVID-19 Prevention Network (a series of site networks combined for efficiency of subject recruitment).
About the UVA COVID-19 Clinic
Part of UVA Health, the COVID-19 Clinic represents a proactive effort in Virginia and includes the Virginia Department of Health and other organizations. They offer free testing in Charlottesville and a number of surrounding counties.
Based in Charlottesville, this academic medical center is associated with the University of Virginia. The UVA Health system includes a medical center (main hospital, children’s hospital and clinic network), school of medicine, school of nursing and health sciences library. This health system offers inpatient and outpatient care, patient education and conducts medical research and education.
The UVA Health System ranks high in the areas of patient care and research as well as medical education. In the past (2016 and 2017), U.S. News & World Report ranked UVAHS as Virginia’s top hospital.
UVA Health maintains 631 beds and helped 882,420 outpatient visits and 60,385 emergency visits as well as 26,159 inpatient encounters during 2020. The system employs over 8,500.
UVA runs a robust and well-known research program. Led by the Office of Research, the Clinical Trials Office supports ongoing clinical trials. UVA’s COVID-19: Research Prioritization Committee was set up during the pandemic to synergize and support COVID-19 research in the region.
As reported in the local Rappahannock News. the study team here at UVA was led by Professor Petri, Shirley and includes Gregory Madden, MD; Chelsea Marie, PhD, Jennifer Sasson, MD; Jae Shin, MD; and Cirle Warren, MD. Igor Shumilin supports the study as Clinical Research Coordinator as well as assistant Rebecca Carpenter. Importantly, the COVID-19 Clinic nurses supporting the REG-COV study include Michelle Sutton, Elizabeth Brooks, Danielle Donigan, Cynthia Edwards, Jennifer Pinnata, Samantha Simmons, and Rebecca Wade.
William A. Petri, MD, PhD, Wade Hampton Frost Professor of Medicine and Vice Chair for Research of the Department of Medicine, and Professor of Medicine, Microbiology, Immunology and Cancer Biology, and Pathology, Medicine: Infectious Diseases and International Health
Debbie Ann Shirley, MBBS, Infectious Diseases, Pediatric, UVA Health