Lack of Ronapreve (REGN-CoV; casirivimab and imdevimab) virological efficacy against the SARS-CoV 2 Omicron variant (B.1.1.529) in K18-hACE2 mice

The Omicron variant (B.1.1.529) of SARS-CoV-2 has placed enormous strain on global healthcare systems since it was first identified by South African researchers in late 2021. Omicron has >50 mutations which mainly occur in the surface spike protein and this has led to rapid assessment of monoclonal antibodies to assess the impact on virus neutralisation. Ronapreve has shown potential application in post-exposure prophylaxis, mild/moderate disease and in seronegative patients with severe COVID19, but several early reports of loss of in vitro neutralisation activity have been documented. Here, the virological efficacy of Ronapreve was assessed in K18-hACE2 mice to provide an in vivo outcome. Ronapreve reduced sub-genomic RNA in lung and nasal turbinate for the Delta variant but not the Omicron variant of SARS-CoV-2 at doses 2-fold higher than those shown to be active against previous variants of the virus. These data add to the growing evidence that the effectiveness of Ronapreve is compromised for the Omicron variant. ### Competing Interest Statement AO and SR are Directors of Tandem Nano Ltd and co-inventors of patents relating to drug delivery. AO has received research funding from ViiV, Merck, Janssen and consultancy from Gilead, ViiV and Merck not related to the current paper. SR has received research funding from ViiV and AstraZeneca and consultancy from Gilead not related to the current paper. No other conflicts are declared by the authors.