Regeneron’s monoclonal antibody treatment lowers the risk of death from COVID-19 by 20% in hospitalized patients with severe illness who haven’t produced a natural immune response, according to preliminary results of the Randomised Evaluation of COVID-19 Therapy (RECOVERY) phase 3 trial. The results were published on the medRxiv preprint server yesterday.
Earlier studies had found that Regeneron’s combination of casirivimab and imdevimab (REGEN-COV) reduces viral load, leads to a shorter duration of symptoms, and cuts the risk of hospitalization and death in nonhospitalized coronavirus patients, and a small study suggested a clinical benefit in hospitalized COVID-19 patients with no antibody response to infection. But the UK-based RECOVERY Trial was the first study large enough to gauge a true effect on death in hospitalized patients.
REGEN-COV works by attacking the coronavirus’s spike protein. Based on those earlier studies, the US Food and Drug Administration issued an emergency use authorization (EUA) for the treatment of patients aged 12 and older with mild to moderate COVID-19 in November 2020.
No mortality benefit in seropositive patients
The randomized, controlled, open-label RECOVERY platform trial involved 9,785 hospitalized COVID-19 patients randomly assigned to receive either REGEN-COV plus usual care or usual care alone from Sep 18, 2020 to May 22, 2021. Roughly one-third of patients were seronegative at baseline, meaning that they hadn’t generated coronavirus antibodies, while half were seropositive, and one-sixth were of unknown serostatus.
Death by 28 days in patients who received only usual care was double that of those who were seronegative (30%) rather than seropositive (15%). In the seronegative group, the antibody cocktail lowered the 28-day death rate by one-fifth compared with usual care alone; 24% of patients in the treatment group died, versus 30% of the usual care group, for a rate ratio [RR] of 0.80). In other words, there were six fewer deaths for every 100 patients who received the treatment.
A test for heterogeneity showed that the effect of treatment in the seronegative group was different from that in the seropositive group (P=0.001). But combining the larger seropositive group with the seronegative patients and those with unknown serostatus revealed no significant effect on death by 28 days; 20% of all patients who received the antibody treatment died, compared with 21% of those in the usual-care group, for an RR of 0.96.
Shorter hospital stay, less need for mechanical ventilation
Joint chief study investigator Peter Horby, MBBS, PhD, of the University of Oxford, said in a RECOVERY trial news release today that there had been doubt about whether antiviral therapies would benefit patients with severe COVID-19. “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,” he said.
Hospital stay was 4 days shorter among seronegative patients who received the antibody cocktail than in those who received only usual care (13 vs 17 days), and the share of patients released from the hospital alive by 28 days was greater (64% vs 58%; RR, 1.19).
Of the seronegative patients who didn’t require invasive mechanical ventilation at the start of the study, the risk of eventually needing it or dying was 30% among those who received REGEN-COV, versus 37% of those in the usual-care group (RR, 0.83). But when combining all patients, regardless of serostatus, no such benefits were observed.
Follow-up is complete for 99% of study participants. According to a Regeneron news release today, the company will request that the EUA for REGEN-COV be expanded to include appropriate hospitalized coronavirus patients.
“The trial was conducted at a time when most patients had not been fully vaccinated,” David Weinreich, MD, a Regeneron executive vice president, said in the company release. “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.”