Monoclonal antibodies (MAB) that combine casirivimab with imdevimab (REGEN COV, Regeneron), protected some contacts from COVID-19. It also reduced the progression of symptoms in others. However, these results were not seen in trials before the emergence of Omicron and Delta 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). Regeneron stated in a statement that REGEN-COV is still active against Delta
The NIH has now only recognized sotrovimab, (GSK), as being active against Omicron. This means that the FDA has approved a supplemental request for intravenous remdesivir for non-hospitalized COVID-19 patients.
It is possible that promising clinical trial results could be distorted by the emergence of new variants, which can lead to a fast-moving campaign against an obscure virus. 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.
The investigators evaluated whether one subcutaneous injection of 600mg of each MAB could prevent or develop COVID-19 in asymptomatic household members of people infected by SARS-CoV-2. They reported an 81.4% decrease in the 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 endpoint was the percentage of participants with seronegative status who had symptomatic COVID-19 within the 28-day assessment period. Secondary endpoints included the duration of symptomatic illness and high viral load.
Meagan O’Brien, MD of Regeneron Pharmaceuticals and co-workers from the COVID-19 Phase 3 Preventive Trial Team reported that the MAB injection significantly slowed the progression to symptomatic diseases (29%) as compared to placebo (42.3%). The treatment also reduced the number of symptomatic week per 1000 participants (895.7 weeks, vs 1,637.4 weekly), which corresponds to a 5.6-day reduction in an individual’s symptoms. Placebo-emergent adverse reactions were more common than active treatment.
O’Brien and his colleagues wrote that “for individuals not protected by vaccinations, complementary approaches such as anti SARS-CoV-2 monoclonal antibody are required.”
Regeneron released a statement advising that “Post-exposure Prophylaxis with Regen-COV isn’t a substitute for immunization against COVID-19.”
