Regeneron's REGEN-COV Shows 20% Reduction in Mortality Among Seronegative Hospitalized COVID-19 Patients in Phase 3 RECOVERY Trial

On June 16, 2021, Regeneron announced that its investigational neutralizing antibody therapy REGEN-COV (casirivimab and imdevimab) achieved positive preliminary results in the phase 3 RECOVERY clinical trial. The trial results showed that, compared to the control group, adding REGEN-COV to standard of care reduced the risk of death by 20% in hospitalized COVID-19 patients who had not mounted a natural antibody response to SARS-CoV-2. The press release noted that RECOVERY is the first large-scale clinical trial to demonstrate that neutralizing antibodies can reduce mortality in hospitalized COVID-19 patients. Regeneron will immediately discuss the latest findings with regulatory authorities and will request that the U.S. FDA expand the Emergency Use Authorization (EUA) to include eligible hospitalized patients.

REGEN-COV is a cocktail therapy consisting of two monoclonal antibodies, administered via intravenous infusion or subcutaneous injection. These two antibodies bind non-competitively to two distinct, non-overlapping sites on the receptor-binding domain (RBD) of the viral spike (S) protein, respectively. This synergistic effect reduces the potential for mutant viruses to evade treatment. REGEN-COV has received Emergency Use Authorization (EUA) for the treatment of adults and adolescents with mild to moderate COVID-19 who test positive for the virus and are at high risk of progression to severe COVID-19 (including hospitalization or death).

This Phase 3 clinical trial enrolled a total of 9,785 hospitalized patients with COVID-19, with a mean age of 62 years. One-third of the hospitalized patients were seronegative (n=3,153), half were seropositive (n=5,272), and one-sixth had unknown serostatus (n=1,360). Patients were randomized to receive standard of care plus REGEN-COV (8000 mg intravenous infusion) or standard of care alone as a control. Follow-up was completed by 99% of participants.

The trial results showed that, consistent with previous studies, when receiving standard care alone, seronegative patients had a day-28 mortality rate twice that of seropositive patients (30% vs. 15%). Compared with the control group, all-cause mortality at day 28 among seronegative patients in the treatment group was reduced by 20% (24% vs. 30%; RR: 0.80; 95% CI: 0.70–0.91; p = 0.001). However, when the analysis was expanded from seronegative patients to the entire patient cohort, the effect of the cocktail therapy on 28-day mortality was no longer statistically significant, with mortality rates of 20% in the treatment group and 21% in the control group (RR: 0.96; 95% CI: 0.86–1.03; p = 0.17).

Furthermore, among seronegative patients, the median length of hospital stay in the trial group was 4 days shorter (13 days vs. 17 days), the proportion of patients discharged by day 28 was also higher (64% vs. 58%), and the risk of the composite endpoint of progression to invasive mechanical ventilation or death was lower in the trial group than in the control group (30% vs. 37%); these benefits were not observed in the overall patient population.

Note: The original text has been abridged.

References:

[1] 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. Retrieved June 16, 2021, from https://investor.regeneron.com/news-releases/news-release-details/regen-covtm-casirivimab-and-imdevimab-phase-3-recovery-trial

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