Efficacy of Bamlanivimab/Etesevimab and Casirivimab/Imdevimab in Preventing Progression to Severe COVID-19 and Role of Variants of Concern

Abstract

Introduction The aim of this study was to evaluate the risk of hospitalization or death in patients infected by SARS-CoV2 variants of concern (VOCs) receiving combinations of monoclonal antibodies (mAbs), bamlanivimab/etesevimab or casirivimab/imdevimab. Methods Observational prospective study conducted in two Italian hospitals (University Hospital of Pisa and San Donato Hospital, Arezzo) including consecutive outpatients with COVID-19 who received bamlanivimab/etesevimab or casirivimab/imdevimab from March 20th to May 10th 2021. All patients were at high risk of COVID-19 progression according to FDA/AIFA recommendations. Patients were divided into two study groups according to the infecting viral strain (VOCs): Alpha and Gamma group. The primary endpoint was a composite of hospitalization or death within 30 days from mAbs infusion. A Cox regression multivariate analysis was performed to identify factors associated with the primary outcome in the overall population. Results The study included 165 patients: 105 were infected by the VOC Alpha and 43 by the VOC Gamma. In the Alpha group, no differences in the primary endpoint were observed between patients treated with bamlanivimab/etesevimab or casirivimab/imdevimab. Conversely, in the Gamma group, a higher proportion of patients treated with bamlanivimab/etesevimab met the primary endpoint compared to those receiving casirivimab/imdevimab (55% vs. 17.4%, p = 0.013). On multivariate Cox-regression analysis, the Gamma variant and days from symptoms onset to mAbs infusion were factors independently associated with higher risk of hospitalization or death, while casirivimab/imdevimab was protective (HR 0.33, 95% CI 0.13–0.83, p = 0.019). Conclusions In patients infected by the SARS-CoV-2 Gamma variant, bamlanivimab/etesevimab should be used with caution because of the high risk of disease progression. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00525-4.

A Learning Health System Randomized Trial of Monoclonal Antibodies for Covid-19

“…Notably, the U.S. federal government reinstated circulation of bamlanivimab-etesevimab on August 27, 2021 in areas where variant resistance to this mAb is < 5%, based on in vitro data of activity against the Delta variant, and lack of activity against the Beta, Gamma, Delta plus, and B.1.621 variants. 31,32 The similar effectiveness of bamlanivimab-etesevimab and casirivimab-imdevimab in the current trial supports this decision. Also aligning with these data is a recent observational study of 165 patients that found no difference in hospitalization or death between bamlanivimab-etesevimab and casirivimab-imdevimab in patients infected with Alpha, but worse outcomes with bamlanivimab-etesevimab in patients infected with Gamma.…”

“…26 A recent observational study reached a different conclusion and found similar effectiveness between bamlanivimab and casirivimab-imdevimab. 31 However, this study analyzed patients treated between November 2020 and February 2021, prior to widespread emergence of variants and U.S. federal decisions to halt bamlanivimab distribution.…”

MicroRNA-Mediated Regulation of the Virus Cycle and Pathogenesis in the SARS-CoV-2 Disease

“…B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529 VOCs (recently renamed by WHO as Alpha, Beta, Gamma, Delta and Omicron, respectively) first identified in the United Kingdom, South Africa, Brazil, India, and Botswana, carry different mutations among which D614G change became dominant early in the pandemic [ 18 ]. VOCs may increase virus transmissibility, disease severity, reduce neutralization by antibodies generated during previous infection or vaccination, and reduce the effectiveness of treatments or vaccines, or diagnostic detection failures [ 15 , 19 , 20 ].…”

Management of COVID patients with convalescent plasma: Do we have the final word?

“…More interestingly, monoclonal antibodies (mAbs) developed from CP, directed against specific target of SGP and selected on the basis of antiviral potency and target affinity showed efficacy in reducing the risk of disease progression and death. Currently approved mAbs have not the same activity against VoC [21] . Ongoing clinical trials are evaluating the safety and efficacy of second-generation mAbs with activity against circulating VoC and more easily administered by IM route.…”

“…The efficacy of CP is likely to depend on the ‘match’ between the strain-specific transfused anti-SARS-CoV-2 antibodies in donor plasma and the infecting virus variant in the recipient. The SARS-CoV-2 variant (B.1.1.7) detected in England in December 2020, spread rapidly to become the dominant SARS-CoV-2 variant in most European countries, including Italy [21] . Whilst B.1.1.7 has changes in the spike glycoprotein that could theoretically modify antigenicity, only modest reductions in neutralization by CP have been reported.…”