Trial Shows Combination Therapy Improves Survival for Certain Patients With COVID-19

Previous trials in non-hospitalized patients with COVID-19 suggested casirivimab and imdevimab reduced viral levels, shortened the time to resolution of symptoms and significantly reduced the risk of hospitalization or death.

A combination monoclonal antibody therapy of casirivimab and imdevimab (Regen-COV; Regeneron) was found to reduce risk of death by 20% in patients hospitalized with COVID-19 who had not mounted their own immune response, according to the results of the RECOVERY trial. RECOVERY was the first trial large enough to determine definitively whether the casirivimab and imdevimab combination reduces mortality in patients hospitalized with severe COVID-19.

“The hope was that by giving a combination of antibodies targeting the SARS-CoV-2 virus we would be able to reduce the worst manifestations of COVID-19,” said Peter Horby, PhD, professor of emerging infectious diseases in the Nuffield Department of Medicine, University of Oxford, in a press release. “There was, however, great uncertainty about the value of antiviral 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.”

Previous phase 3 trials in non-hospitalized patients with COVID-19 suggested casirivimab and imdevimab reduced viral levels, shortened the time to resolution of symptoms and significantly reduced the risk of hospitalization or death. Further, a phase 1/2 trial in hospitalized patients showed the therapy rapidly reduced viral levels, and preliminary evidence suggested that it lowered the risk of death or receiving mechanical ventilation. This benefit was driven by seronegative patients who entered the trial without having mounted a natural antibody response of their own, and in the absence of treatment, seronegative patients had higher mortality rates than seropositive patients who had already mounted their own immune response.

The RECOVERY trial was designed based on the data from this phase 1/2 trial, focusing primarily on seronegative patients. According to the authors of the study, participants receiving usual care alone had a 30% mortality rate at day 28 if they were seronegative, compared to 15% if they were seropositive. The primary outcome of RECOVERY demonstrated that adding Regen-COV 8000mg to usual care reduced all-cause mortality by 20% in seronegative patients compared to usual care alone. Combining the larger seropositive group with the seronegative patients, there was no longer a significant effect on 28-day mortality.

“Definitive Phase 3 trials have now demonstrated that Regen-COV can alter the course of COVID-19 infection from prevention, to very early infection, all the way through to when patients are on a ventilator in the hospital," said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron. "We are incredibly grateful to the RECOVERY team, participating investigators and patients for conducting this in-depth analysis, and hope that the results mean that even more patients may soon be able to benefit from this life-saving medicine. We intend to rapidly discuss these results with regulatory authorities, including in the U.S. where we will ask for our EUA to be expanded to include appropriate hospitalized patients.”

REFERENCE

Regen-COV™ (casirivimab and imdevimab) phase 3 recovery trial meets primary outcome, improving survival in hospitalized COVID-19 patients lacking an immune response to SARS-CoV-2 [news release]. Regeneron; June 16, 2021. Accessed June 21, 2021. https://investor.regeneron.com/index.php/news-releases/news-release-details/regen-covtm-casirivimab-and-imdevimab-phase-3-recovery-trial