The FDA on Friday expanded the emergency use authorization (EUA) it granted in November to Regeneron Pharmaceuticals for its two-antibody “cocktail” REGEN-COV™ (casirivimab and imdevimab) to allow its use in patients seeking protection from COVID-19 following exposure to someone infected with SARS-CoV-2.
The expanded EUA also authorizes REGEN-COV for people deemed at high risk of exposure to an infected individual in institutions such as nursing homes or prisons because they are not fully vaccinated or are not expected to develop an antibody response to vaccination.
In addition, the expanded EUA allows for monthly administration of REGEN-COV in people aged 12 and older who require repeat dosing for ongoing exposure.
“[Friday’s] FDA authorization enables certain people at high risk of developing severe COVID-19 infection to access REGEN-COV if they have been exposed to the virus—the first time an antibody treatment has been authorized for this purpose,” George D. Yancopoulos, MD, PhD, Regeneron’s president and CSO, said in a statement.
Regeneron cited positive data for REGEN-COV in a pivotal Phase III trial (2069A; NCT04452318) run jointly with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
The trial assessed the antibody cocktail for post-exposure prophylaxis of COVID-19 in household contacts of individuals infected with SARS-CoV-2 (index case). The data showed REGEN-COV 1,200 mg administered subcutaneously reduced the risk of symptomatic infections by 81% in those who were not infected when they entered the trial.
A total 1,505 participants in the trial (753 treated with REGEN-COV, 752 given placebo) were not infected when they entered the trial. In a post-hoc analysis in the subgroup of participants who met the criteria for high risk for progression to severe COVID-19 (570 REGEN-COV, 567 placebo), there was a 76% risk reduction in COVID-19 with REGEN-COV treatment compared to placebo, Regeneron said.
Reducing symptomatic infections
Based on post-hoc analysis, REGEN-COV was also found to have reduced the risk of symptomatic infections by 62% in a larger group of 2,378 asymptomatic participants (1,201 REGEN-COV, 1,177 placebo), regardless of infection status.
“We continue to work with the FDA as it undertakes its review of REGEN-COV in a broader group of people including in a pre-exposure prophylactic setting for people who are immunocompromised, and in patients hospitalized due to COVID-19,” Yancopoulos added.
REGEN-COV’s emergency authorization does not allow for its use as a substitute for vaccination against COVID-19, or for pre-exposure prevention of the disease.
Both casirivimab and imdevimab are designed to bind non-competitively to the receptor-binding domain (RBD) of SARS-CoV-2’s spike protein. According to a paper published in Science, casirivimab targets the spike-like loop region on one edge of the ACE2 interface. The fragment antigen-binding region of casirivimab binds the RBD from the top, where it collides with ACE2, while imdevimab only binds to the front or the lower left side of the RBD.
In a study published in the journal Cell, REGEN-COV retained its potency against the main variants of concern circulating within the United States—including Delta (B.1.617.2; first identified in India), Gamma (P.1; first identified in Brazil), and Beta (B.1.351; first identified in South Africa).
Before patients can be treated with REGEN-COV2 under the EUA, they must weigh at least 40 kilograms (about 88 pounds) and be deemed at high risk for progressing to severe COVID-19 and/or hospitalization. That high-risk category includes adults who are ages 65 or older, or who have chronic medical conditions.