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

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEYWORDS:

• Bamlanivimab
• ly-cov555
• covid-19
• etesevimib: monoclonal antibody
• pandemic
• sars-cov-2
• spike protein

Article highlights

• The development of anti-COVID-19 monoclonal antibodies appeared a promising strategy to treat critically ill patients and to reduce pandemic pressure on hospitals

• Bamlanivimab was the first monoclonal antibody developed from human convalescent plasma to receive authorization for emergency use

• In the pre-clinical trial, bamlanivimab, administered IV 24 hours before intranasal and intratracheal inoculation of SARS-CoV-2, has been shown to inhibit viral load in respiratory tissues in primate models

• In clinical trials, bamlanivimab has been shown to be effective in reducing hospitalization in patients with mild to moderate COVID-19, but no efficacy in critically ill patients

• The occurrence of SARS-CoV-2 variants and some pharmacokinetic limitations are the basis of a reduced efficacy that led the FDA to withdraw the emergency authorization for bamlanivimab monotherapy, while leaving it for the bamlanivimab-etesevimab combination

• The future of COVID-19 mAb therapy is uncertain due to problems related to viral resistance, pharmacokinetics, and economic sustainability

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.