Antibody cocktail improves survival in seronegative hospitalised COVID-19 patients
Phase III data shows REGEN-COV™ (casirivimab and imdevimab) reduced risk of death by 20 percent in hospitalised COVID-19 patients lacking an immune response to SARS-CoV-2.
According to a report, adding Regeneron’s investigational COVID-19 antibody cocktail REGEN-COV™ (casirivimab and imdevimab) to usual care reduced the risk of death by 20 percent in hospitalised patients who had not mounted a natural antibody response against SARS-CoV-2, the virus that causes COVID-19, compared to usual care on its own. The results are from the RECOVERY trial which enrolled 9,785 patients in the UK.
“These results are very exciting. The hope was that by giving a combination of antibodies targeting the SARS-CoV-2 virus [, which causes COVID-19,] we would be able to reduce the worst manifestations of COVID-19,” said Sir Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine at the University of Oxford and Joint Chief Investigator for the RECOVERY trial. “There was, however, great uncertainty about the value of anti-viral therapies in late-stage COVID-19 disease. It is wonderful to learn that even in advanced COVID-19 disease, targeting the virus can reduce mortality in patients who have failed to mount an antibody response of their own.”
RECOVERY is the first trial large enough to definitively determine whether REGEN-COV reduces mortality in patients hospitalised with severe COVID-19. Previous Phase III trials in non-hospitalised COVID-19 patients have shown that the antibody cocktail reduced viral levels, shortened the time to resolution of symptoms and significantly reduced the risk of hospitalization or death. Additionally, Phase I/II data showed that, in hospitalised patients, REGEN-COV also rapidly reduced viral levels, with preliminary evidence suggesting that it lowered the risk of death or receiving mechanical ventilation, with the benefit driven by patients who entered the trial without having mounted a natural antibody response of their own (seronegative); and in the absence of REGEN-COV treatment, seronegative patients had higher mortality rates than patients who had already mounted their own immune response (seropositive).
Based on that Phase I/II data, the independently-run RECOVERY trial prospectively focused on seronegative patients. Similar to the prior trial, patients in RECOVERY who received usual care alone had double the mortality rate at day 28 if they were seronegative (30 percent) compared to seropositive (15 percent). Approximately one-third of hospitalised patients were seronegative (n=3,153), one-half were seropositive (n=5,272) and one-sixth had unknown serostatus (n=1,360). The mean age of patients for this comparison was 62 years and more than 90 percent received corticosteroids across all groups.
The primary outcome of RECOVERY showed that adding REGEN-COV 8,000mg to usual care reduced all-cause mortality by 20 percent in seronegative patients (primary analysis population), compared to usual care alone. Overall, 24 percent of patients in the REGEN-COV group died versus 30 percent in the usual care group by day 28. In the overall trial population (seropositive, seronegative and unknown serostatus), there was no longer a significant effect on 28-day mortality (20 percent of REGEN-COV patients died versus 21 percent in the usual care group).
Among seronegative patients in the RECOVERY trial, the median duration of hospital stay was four days shorter in the REGEN-COV group (13 days versus 17 days) and the proportion of patients discharged alive by day 28 was greater (64 percent versus 58 percent). Among the seronegative patients not on invasive mechanical ventilation at baseline, the risk of progressing to the composite endpoint of invasive mechanical ventilation or death was lower among the REGEN-COV group than the usual care group (30 percent versus 37 percent). No such benefits were seen in the overall trial population.
“The RECOVERY trial has shown that in patients who had not made their own antibodies against SARS-CoV-2, treating them with REGEN-COV antibodies dramatically reduced their risk of dying or being on a ventilator and also shortened how many days they remained in the hospital,” said Dr David Weinreich, Executive Vice President, Global Clinical Development at Regeneron. “The trial was conducted at a time when most patients had not been fully vaccinated. These results provide hope to patients who have a poor immune response to either the vaccine or natural infection, as well as those who are exposed to variants for whom their existing antibodies might be sub-optimal.”
Regeneron is currently in discussions with the US Food and Drug Administration (FDA) to expand the current emergency use authorisation (EUA) for REGEN-COV to other populations, including the prevention and hospitalised patient settings. Later this summer, Regeneron expects to submit a full Biologics License Application (BLA) for REGEN-COV.