An overview of the preclinical discovery and development of bamlanivimab for the treatment of novel coronavirus infection (COVID-19): reasons for limited clinical use and lessons for the future.

: In the COVID-19 pandemic emergency, research has been oriented toward the development of therapies that could cure critically ill patients and treatments that can reduce the number of hospitalized patients, in order to ease the pressure on health-care systems. Bamlanivimab, developed from human convalescent plasma, was the first monoclonal antibody to become available for emergency use in several countries. Expectations related to its use in COVID-19 patients as a single agent have been largely disregarded, especially against E484K-carrying SARS-CoV-2 variants.: In this drug discovery case history, the development of the drug is described starting from the identification and selection of the antibody, from the pre-clinical and clinical trials up to the post-authorization phase.: Bamlanivimab has shown some efficacy in patients with mild to moderate COVID-19. Initially approved as a monotherapy, due to poor efficacy it is currently only usable in combination with etesevimab. Pharmacokinetic limitations and mainly the onset of SARS-CoV-2 variants are the main reasons for this limited clinical use. The use in preventing hospitalization also has ethical limits related to the sustainability of care, especially if, considering similar effectiveness, bamlanivimab is compared with convalescent plasma.