Regeneron Pharmaceuticals and partner Roche reported positive results from a phase 3 study, showing that a subcutaneous formulation of the antibody cocktail REGEN-COV (casirivimab with imdevimab) reduced the risk and burden of COVID-19 among household contacts of SARS-CoV-2-infected individuals. According to the findings, REGEN-COV cut the risk of symptomatic COVID-19 by 81% among people who were not infected when they entered the 2069A trial, meeting the primary endpoint.
“Convenient subcutaneous administration of REGEN-COV could help control outbreaks in high-risk settings where individuals have not yet been vaccinated, including individual households and group living settings,” commented Myron Cohen, who helped lead the study on behalf of the US National Institute of Allergy and Infectious Diseases.
The FDA authorised REGEN-COV for emergency use last November, with casirivimab 1200 mg and imdevimab 1200 mg to be given as a single intravenous (IV) infusion, for a total dose of 2400 mg. Last month, in reporting results from another phase 3 trial showing that REGEN-COV lowered the likelihood of at-risk COVID-19 patients progressing to hospitalisation or death, the companies highlighted a phase 2 companion study in which the subcutaneous formulation of REGEN-COV was comparable to the IV doses at significantly decreasing viral load over the first week.
The 2069A trial enrolled 1505 people, who did not have anti-SARS-CoV-2 antibodies or any COVID-19 symptoms, but who lived in the same household as a person who tested positive for SARS-CoV-2 within the prior four days. Participants were randomized to receive REGEN-COV, administered as a single subcutaneous dose of 1200 mg, or placebo. Initial data from the study released in January showed that it cut both symptomatic and asymptomatic infection rates by roughly half, and was also 100% effective at preventing symptomatic infections.
Lower viral load, shorter symptom duration
On Monday, the companies said that for the primary endpoint, 11 patients treated with REGEN-COV experienced symptomatic SARS-CoV-2 infection through day 29, compared to 59 for placebo, for a risk reduction of 81%. Regeneron and Roche said the dual antibody therapy also protected household contacts from exposure to SARS-CoV-2 by 72% in the first week, where the case counts were nine for the REGEN-COV group and 32 for placebo. Protection jumped to 93% in subsequent weeks, with two events and 27 events, respectively, for the two groups. Four placebo participants were either hospitalised or visited the emergency room because of COVID-19 during the 29-day assessment period, whereas there were none in the treatment arm.
Among people who developed symptomatic infections, results suggested REGEN-COV helped clear the virus faster and led to shorter symptom duration. Specifically, recipients had high viral load for an average 0.4 weeks, compared to an average 1.3 weeks for placebo. In addition, participants in the REGEN-COV arm had symptoms for an average of 1.2 weeks, versus an average of 3.2 weeks for placebo. Overall, REGEN-COV recipients experienced a cumulative total of 13 weeks with symptoms, compared with 188 weeks for placebo, for a reduction of 93%. Regeneron did not disclose how many volunteers tested positive for COVID-19 without showing symptoms, but a company spokesperson said it plans to do so in the future.
Meanwhile, in a cohort of 204 recently-infected asymptomatic patients, Roche noted that REGEN-COV reduced the overall risk of progressing to symptomatic COVID-19 by 31%. The therapy also decreased the total number of weeks with high viral load by 40%, and the cumulative total number of weeks with symptoms by 45%, compared with placebo.
Option for unvaccinated people
Adverse events (AEs) were reported in 20% of REGEN-COV participants and in 29% of those given placebo, while serious AEs were similar between the two groups, occurring at a rate of 1% each. Further, no individuals from either arm withdrew from the trial due to AEs, and while there were two deaths in each of the groups in the trial, none were attributed to COVID-19 or the antibody cocktail.
“REGEN-COV…may help provide immediate protection to unvaccinated people who are exposed to the virus, and we are also working to understand its potential to provide ongoing protection for immunocompromised patients who may not respond well to vaccines,” said George Yancopoulos, chief scientific officer at Regeneron. He added that the company intends to “rapidly [discuss] these results with regulatory authorities.”