REGEN-COV Antibody Cocktail Significantly Improves Survival in Hospitalized COVID-19 Patients Lacking Immune Response Amid Global Cases Surpassing 177 Million

June 16, 2021 /Bio ValleyBIOON/ -- At present, the COVID-19 epidemic overseas continues to spread rapidly. According to Baidu's 《Real-time Novel Coronavirus Pneumonia EpidemicBig DataReport》, as of 24:00 on June 16, 2021, the global cumulative number of confirmed cases exceeded 170 million (177.55 million), with over 3.84 million deaths.

Recently, Regeneron announced the largest-scale study evaluating monoclonal antibody therapy for hospitalized patients with severe COVID-19.Clinical TrialsPositive results from the UK RECOVERY trial. Data show that,In patients who failed to mount a natural antibody response against the novel coronavirus (SARS-CoV-2), the antibody cocktail therapy REGEN-COV (casirivimab and imdevimab) combined with standard care reduced the risk of death by 20% compared with standard care alone.

REGEN-COV is an antibody cocktail therapy comprising two antibodies that target two independent, non-overlapping epitopes within the receptor-binding domain of the SARS-CoV-2 spike protein. Acting synergistically, they reduce the risk of viral escape mutations and protect the population against viral variants harboring spike protein mutations.REGEN-COV can prevent SARS-CoV-2 infection and treat infection by accelerating viral clearance.

Peter Horby, Joint Chief Investigator of the RECOVERY trial and Professor of Emerging Infectious Diseases at the Nuffield Department of Medicine, University of Oxford, said: “These results are very exciting. We hope that through antibody cocktail therapy, we can reduce the worst manifestations of COVID-19. Currently, there is significant uncertainty regarding the value of antiviral therapy in late-stage COVID-19 disease. We are pleased to learn that even in late-stage COVID-19 disease, virus-targeted treatments can reduce mortality among patients who have not mounted an antibody response.”

David Weinreich, Executive Vice President of Global Clinical Development at Regeneron, stated: "The RECOVERY trial demonstrated that in patients who have not generated their own SARS-CoV-2 antibodies, treatment with the REGEN-COV antibody cocktail significantly reduces the risk of death or mechanical ventilation and also shortens the length of hospital stay."This trial was conducted when most patients had not yet been fully vaccinated (September 18, 2020–May 22, 2021). These results offer hope for patients with a suboptimal immune response to vaccination or natural infection, as well as for those exposed to viral variants against whom their existing antibodies may be less effective.”

REGEN-COV was developed for the treatment and prevention of COVID-19 infection. In August 2020, Roche and Regeneron entered into a strategic collaboration to develop, manufacture, and distribute REGEN-COV globally. The therapy will provide a much-needed treatment option for patients already exhibiting COVID-19 symptoms, and has the potential to prevent infection in high-risk individuals exposed to the virus, thereby helping to slow the spread of the global pandemic.

In the United States,FDAREGEN-COV has been granted an Emergency Use Authorization (EUA) for the treatment of high-risk patients recently diagnosed with mild to moderate COVID-19, specifically: pediatric and adult patients aged ≥12 years and weighing ≥40 kg who have tested positive for SARS-CoV-2 via a direct viral test and are at high risk for progressing to severe COVID-19 and/or hospitalization. Recently announced Phase 3 trial results demonstrate that REGEN-COV reduces the risk of hospitalization or death by 70% in high-risk non-hospitalized patients.

REGEN-COV (Image source: maroc-hebdo.press.ma)

RECOVERY was the first trial large enough to determine whether REGEN-COV could reduce mortality among hospitalized patients with severe COVID-19. Previous Phase 3 trials conducted in non-hospitalized COVID-19 patients demonstrated that REGEN-COV reduced viral load, shortened the time to symptom resolution, and significantly reduced the risk of hospitalization or death. In a Phase 1/2 trial conducted in hospitalized patients, REGEN-COV also rapidly reduced viral load, with preliminary evidence indicating that it reduced the risk of death or receipt of mechanical ventilation; this benefit was driven by patients who had not mounted a natural antibody response (seronegative) at trial entry; in the absence of REGEN-COV treatment, the mortality rate among seronegative patients was higher than that of those who had already producedAutoimmunityPatients with a response (serologically positive).

Based on the aforementioned Phase 1/2 data, the independently conducted RECOVERY trial prospectively focused on seronegative patients. Consistent with prior trials, among those receiving standard care alone, Day 28 mortality was twice as high in seronegative patients (30%) as in seropositive patients (15%). In the RECOVERY trial, approximately one-third of hospitalized patients were seronegative (n=3,153), half were seropositive (n=5,272), and one-sixth had unknown serostatus (n=1,360). The mean age of patients in the comparison was 62 years, and over 90% across all groups received corticosteroid therapy.

The primary results of the RECOVERY trial showed that, compared with standard care alone, adding REGEN-COV 8000 mg to standard care reduced all-cause mortality by 20% in seronegative patients (the primary analysis population) (28-day mortality: 24% in the REGEN-COV group vs. 30% in the standard care group; risk ratio [RR] = 0.80; 95% CI: 0.70–0.91; p = 0.001). When the larger seropositive group (along with patients of unknown serostatus) was combined with the seronegative patients, there was no longer a significant effect on 28-day mortality (overall mortality: 20% in the REGEN-COV group vs. 21% in the standard care group; RR = 0.96; 95% CI: 0.86–1.03; p = 0.17).

In seronegative patients in the RECOVERY trial, the REGEN-COV group had a 4-day reduction in the median duration of hospitalization (13 days vs. 17 days) and a higher proportion of patients discharged alive by day 28 (64% vs. 58%; RR=1.19; 95% CI: 1.08–1.30). Among seronegative patients not receiving invasive mechanical ventilation at baseline, the REGEN-COV group had a lower risk of the composite endpoint of progression to invasive mechanical ventilation or death compared with the usual care group (30% vs. 37%; RR=0.83; 95% CI: 0.75–0.92). This benefit was not observed in the overall trial population (comprising seronegative, seropositive, and status-unknown patients).

Multiple analyses, including a recent study published in the academic journal *Cell*, have demonstrated that REGEN-COV retains efficacy against the major viral variants circulating in the United States; therefore, REGEN-COV remains available for use in all 50 states. REGEN-COV maintains efficacy against viral variants including P.1 (first identified in Brazil and currently classified by the World Health Organization [WHO] as Gamma [γ]), B.1.351 (first identified in South Africa and currently classified by the WHO as Beta [β]), and B.1.162.2 (first identified in India and currently classified by the WHO as Delta [δ]). Currently, in eight U.S. states (Arizona, California, Florida, Illinois, Indiana, Massachusetts, Oregon, and Washington), the combined frequency of the P.1 and B.1.351 variants has exceeded that of the new`Diagnosis`10% of COVID-19 cases, the prevalence of these and other variants remains under close monitoring. (Bioon.com)

Original source: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