Casirivimab/imdevimab protected uninfected contacts from COVID-19 and reduced symptomatic infections in trials before Omicron emerged.
The monoclonal antibody (MAB) combination of casirivimab and imdevimab (REGEN-COV, Regeneron) protected some uninfected contacts from developing COVID-19 and reduced progression of symptoms in others, but in trials conducted before emergence of Delta and Omicron variants.
Despite the FDA authorizing emergency use of the MAB combination in November for treatment and post-exposure prophylaxis in certain high risk individuals,the National Institutes of Health (NIH) guidelines, updated January 19, predict that the Omicron variant will have "markedly reduced" susceptibility to both casirivimab/imdevimab and to bamlanivimab/etesevimab (Lilly, emergency use authorized December 22). In a released statement, Regeneron noted that REGEN-COV remains active against Delta
With the NIH now recognizing only sotrovimab (GSK) as active against Omicron, among the 3 MAB products with emergency authorization for early treatment of COVID-19, the updated guidelines recommend intravenous remdesivir (Veklury, Gilead) as an additional option.The FDA approved a supplemental application for remdesivir to treat non-hospitalized patients with mild to moderate COVID-19 on January 21.
In this fast moving campaign against an elusive virus, it is an unfortunate possibility that promising clinical trial results can be confounded even as they are reported, by emergence of new variants "of interest". The trials demonstrating potential utility of casirivimab/imdevimab in non-infected contacts and in early treatment of the infection were conducted in Romania, Moldova and the US prior to the circulation of the Delta and Omicron variants; and now offer less promise for regions such as the US in which Omicron is dominant.
In the first part of the placebo-controlled, phase 3 trial, the investigators assessed whether a single subcutaneous injection containing 600mg of each MAB would prevent infection or the development of COVID-19 among asymptomatic household contacts of persons infected with SARS-CoV-2.They reported an 81.4% reduction in risk.
In the recently reported second part of the trial, the course of the infected close contacts who had been randomized to receive either active treatment (n=155) or placebo (n=156) were monitored for a 28-day efficacy assessment period, and through 7 months of follow-up.Approximately 1/3 of the cohort had 1 or more risk factors for severe COVID-19, the mean age was 41 years, and approximately 1/2 were women.
The primary end point was the proportion of seronegative participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. Secondary endpoints were the number of weeks of symptomatic infection and of high viral load.
Meagan O'Brien, MD, Regeneron Pharmaceuticals, and colleagues of the COVID-19 Phase 3 Prevention Trial Team, reported that the MAB injection significantly prevented progression to symptomatic disease (29%) compared to placebo (42.3%). In addition, the treatment reduced the number of symptomatic weeks per 1000 participants (895.7 weeks vs 1,637.4 weeks); corresponding to an approximate 5.6 day reduction in an individual's symptoms. Treatment-emergent adverse events were more common with placebo than the active treatment.
"For individuals not protected by vaccination, complimentary approaches such as anti-SARS-CoV-2 monoclonal antibodies are needed," O'Brien and colleagues wrote.
The statement released by Regeneron advises, however, "Post-exposure prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19."