REGEN-COV Antibody Cocktail Clinical Outcomes Study in Covid-19 Outpatients

Abstract

Background: REGEN-COV antibody cocktail (casirivimab with imdevimab) rapidly reduced viral load and decreased medically-attended visits in the phase 1/2 portion of this trial; REGEN-COV, retains activity in vitro against emerging SARS-CoV-2 variants of concern. Methods: The phase 3 portion of this adaptive, randomized, master protocol, included 4,057 Covid-19 outpatients with one or more risk factors for severe disease. Patients were randomized to a single treatment of intravenous placebo, or various doses of REGEN-COV, and followed for 28 days. The prespecified hierarchical analysis first compared REGEN-COV 2400mg dose vs concurrent placebo, then compared the 1200mg dose vs concurrent placebo, for endpoints assessing risk of hospitalization or death, and time to symptom resolution. Safety was evaluated in all treated patients. Results: Both REGEN-COV 2400mg and 1200mg significantly reduced Covid-19-related hospitalization or all-cause death compared to placebo (71.3% reduction [1.3% vs 4.6%; p<0.0001] and 70.4% reduction [1.0% vs 3.2%; p=0.0024], respectively). The median time to resolution of Covid-19 symptoms was 4 days shorter in both dose arms vs placebo (10 vs 14 days; p<0.0001). Efficacy of REGEN-COV was consistent across subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. REGEN-COV more rapidly reduced viral load than placebo. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200mg (1.1%) and 2400mg (1.3%) groups and grade ≥2 infusion-related reactions were infrequent (<0.3% in all groups). Conclusions: Treatment with REGEN-COV was well-tolerated and significantly reduced Covid-19-related hospitalization or all-cause death, rapidly resolved symptoms, and reduced viral load. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.)

The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies

“…We extend these findings by showing that escape variants can also be efficiently selected in vivo upon treatment with individual antibodies, independent of dosage or treatment setting (prophylaxis or therapy), whereas the REGEN-COV combination fully protects against development of such resistance. Importantly, we confirm these findings in humans; we investigated the genetic diversity of the entire spike protein across 4,882 samples from 1,000 outpatients or hospitalized patients with confirmed COVID-19 from ongoing phase 1-3 trials (Weinreich et al, 2020(Weinreich et al, , 2021; https://clinicaltrials.gov; NCT04666441, NCT04426695, and NCT04452318). Analysis of baseline and post-treatment sequence diversity in placebo and REGEN-COVtreated patients demonstrated that the non-competing antibody combination protects against selection of drug resistant variants.…”

Subcutaneous REGEN-COV Antibody Combination in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial

“…19 The two-antibody combination reduces the risk of emergence of treatment-induced SARS-CoV-2 variants and retains neutralization potency in vitro against already-circulating variants of concern or interest (VOC/VOIs), including B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617 (delta), and B.1.427/429. [20][21][22][23] REGEN-COV has proven effective in treating COVID-19 outpatients 24,25 and is currently authorized in the U.S. under an emergency use authorization (EUA) for the treatment of mild-to-moderate COVID-19 and for postexposure prophylaxis in certain individuals exposed to or at high risk of exposure to a SARS-CoV-2-infected individual. 26,27 We conducted a phase 3, randomized controlled trial in asymptomatic household contacts of SARS-CoV-2-infected individuals to assess whether subcutaneous REGEN-COV 1200 mg (600 mg of each monoclonal antibody) may prevent infection and/or COVID-19 in this high-risk setting.…”

Ronapreve for prophylaxis and treatment of covid-19

“…On 20 August 2021, Ronapreve received conditional marketing authorisation for the prevention and treatment of covid-19 in the UK 1. Ronapreve (REGEN-COV in the US) comprises two monoclonal antibodies, casirivimab and imdevimab, that target the SARS-CoV-2 spike protein to reduce the risk and severity of covid-19 in selected patients 2345. Although Ronapreve’s approval represents a welcome expansion in the armamentarium against covid-19, it also brings difficult questions about who should be eligible for treatment.…”

“…The conditional marketing authorisation was based on two pivotal trials 234. The first randomised 4567 outpatients with covid-19 to placebo or intravenous Ronapreve 23.…”

“…The conditional marketing authorisation was based on two pivotal trials 234. The first randomised 4567 outpatients with covid-19 to placebo or intravenous Ronapreve 23. Eligible patients had at least one risk factor for severe disease, symptom onset within 7 days, and a positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) result within 72 hours.…”