Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant

Abstract

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.

Treatment of Infants and Children With SARS-CoV-2 Monoclonal Antibodies: A European Case Series

“…In adult studies, allergic reactions, anaphylaxis, or infusion-related reactions were the main reported serious side effects occurring in bamlanivimab (2.3% of patients experienced local reactions), 14 casirivimab/imdevimab (1.4% grade ≥2 infusionrelated reaction), 15 sotrovimab (1% infusion-related reactions and 1 patient, ie, <1%, with infusion-related dyspnea) 16,17 and regdanvimab (2.9% with hypertriglyceridemia, 1% infusion-related reaction, 2 patients, ie, 8.3%, in the phase 1 study with hepatocellular injury). [18][19][20] Although studies with head-to-head comparisons are lacking, mAbs are thought to cause fewer side effects such as serum sickness, allergic reactions or life-threatening anaphylaxis than traditional serum therapy or polyclonal preparations (eg, convalescent plasma). 21 Due to data scarcity in children, despite promising studies in adults, a United States expert consortium in 2021 did not recommend the routine use of imdevimab and bamlanivimab in children, even in cases of high risk for disease progression.…”

Evidence of the Clinical Efficacy of Antiviral Agents against SARS-CoV-2

“…This neutralizing antibody shows some efficacy in vitro in decreasing viral loads of various SARS-CoV-2 isolates, e.g. South-African and a Korean, as well as the wild type of the virus [68,69]. CT-P53 showed significantly inhibited viral replication in vivo [69] and a clinical study involving approximately 200 patients indicated that this agent increases viral clearance and decreases time to negative conversion as well as hospitalization [70].…”

Potent neutralizing anti-SARS-CoV-2 human antibodies cure infection with SARS-CoV-2 variants in hamster model

“…Tixagevimab did not show activity against omicron either, while cilgavimab retained some activity (albeit 15-fold lower), resulting in a 42-fold reduction of the activity of the tixagevimab/cilgavimabb cocktail against omicron. On the other hand, sotrovimab and bebtelovimab are still retaining activity against beta, delta, and omicron (Cameroni et al, 2021;Corti et al, 2021;Ryu and Kang, et al, 2021;Ryu and Song, et al, 2021;Hoffmann et al, 2021;Planas et al, 2021;Westendorf et al, 2022;Ju et al, 2022;Li et al, 2022;Touret et al, 2022). This demonstrates that several of the commercially available therapeutic mAbs lose their activity against multiple SARS-CoV-2 variants of concern (VoC).…”