Monoclonal Antibody for Patients with Covid-19

Abstract

The ACTIV-3/TICO LY-CoV555 Study Group (Dec. 22)1 hypothesized that low penetration of the antibody into the infected lungs might explain the lack of benefit of bamlanivimab (LY-CoV555) in hospitalized patients with coronavirus disease 2019 (Covid-19). However, we previously measured transudation of human immunodeficiency virus type 1 (HIV-1) monoclonal antibodies (VRC07-523 and PGT121) into tissues of 1-month-old rhesus macaques as part of a study to assess the effectiveness of monoclonal antibodies as postexposure prophylaxis.2 We detected high concentrations of passively transferred antibodies in the lungs of the two macaques (250 ng per milliliter in one and 285 ng per milliliter in the other) after subcutaneous administration of 10 mg per kilogram of body weight of monoclonal antibody cocktail. The concentration of antibody in the lungs was higher than the mean concentration detected in 26 other tissues (184 ng per milliliter); monoclonal antibody biodistribution was not affected by the virus in challenged animals.Our observations suggest that the rapid selection of neutralization-resistant variants, rather than biodistribution, might have undermined the efficacy of bamlanivimab in this trial. This hypothesis is supported by recent data provided by Regeneron about the preliminary efficacy of the combination of casirivimab and imdevimab in reducing the risk of death or mechanical ventilation in hospitalized patients with Covid-19.