Regeneron Pharmaceuticals, Inc., has announced Phase 3 findings from a randomized, double-blind, placebo-controlled study of recently infected asymptomatic COVID-19 patients. Their study assessed the efficacy and safety of REGEN-COV, a monoclonal antibody cocktail comprised of casirivimab and imdevimab.
Katharine J. Bar, MD, an infectious disease specialist at Penn Medicine, was the co-principal investigator for the trial.
Dr. Bar is also Director, Virology Core, Penn Center for AIDS Research, and Assistant Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania.
In a recent interview, Dr. Bar elaborated on the importance of early prevention of SARS-CoV-2 transmission.
“COVID-19 transmission often occurs via infected people who don’t yet have symptoms,” she said. “So it’s critical that we rapidly diagnose and treat these individuals for their own health and to prevent transmission.”
REGEN-COV Trial Details
The trial enrolled 204 asymptomatic individuals from childhood* through adulthood who tested positive for SARS-CoV-2 but did not have anti-virus antibodies at baseline. All trial participants were randomized to receive either a single injection of REGEN-COV (1,200 mg) or a placebo. The primary study endpoint was prevention of progression from asymptomatic to symptomatic disease.
Previously, REGEN-COV was available only as an IV infusion; an injectable format was used in the Phase 3 trial.
Trial Outcomes
The trial met all primary and key secondary endpoints:
- Reduced risk of progressing to symptomatic COVID - One shot of REGEN-COV reduced the patients’ overall risk of progressing to symptomatic COVID-19 by 31% (primary endpoint.) Infections were cut by 76% after the third day. In a second phase 3 trial reported on the same day by Regeneron, a single injection reduced infections by 81% in those not infected when they entered the trial.
- Reduced viral burden by more than 90% and shortened symptom duration.
- Reduced length of presentation by nearly half and reduced ER visits In addition to reducing the risk of symptomatic infections, the total number of weeks patients experienced symptoms was nearly cut in half (45%) with REGEN-COV.
Researchers also found that six patients in the placebo arm were either hospitalized or visited an emergency room during the trial period, versus none of the patients in the treatment arm.
"These data pave the way for REGEN-COV to be used before patients become symptomatic, with a more convenient subcutaneous administration,” Dr. Bar concluded.
How do Monoclonal Antibodies Work Against COVID-19?
Monoclonal antibodies are laboratory-made proteins that act like antibodies in the immune system. Like human-made antibodies, monoclonal antibodies also have the ability to fight off harmful pathogens.
According to Regeneron, REGEN-COV was designed specifically to block infectivity of SARS-CoV-2, the virus that causes COVID-19.
The two potent, virus-neutralizing antibodies that form the REGEN-COV cocktail bind non-competitively to different, non-overlapping epitopes on the critical receptor binding domain of the virus spike protein. Casirivimab targets the spike loop region on one edge of the ACE2 interface, and imdevimab binds to the front or the lower left side of the receptor binding domain.
The data is encouraging: There is evidence that REGEN-COV retains neutralization activity against mutant viruses and spike variants, including B117, B1352, and P1.
Under an EUA issued by the U.S. Food and Drug Administration (FDA), REGEN-COV is currently available in the U.S. to treat mild-to-moderate COVID-19 in adults, as well as in pediatric patients (with signed consent) at least 12 years of age and weighing at least 40 kg, who have received positive results of direct SARS-CoV-2 viral testing and are at high risk for progressing to severe COVID-19 and/or hospitalization.
Read more on Reuters: “Regeneron to seek U.S. OK for COVID-19 cocktail to be used for prevention(April 12, 2021)
Additional Penn Resources