Medlior was pleased to work with the Canadian Agency for Drugs and Technologies in Health (CADTH) to prepare a report on virus-neutralizing monoclonal antibodies for the treatment of SARS-CoV-2 infection, as part of CADTH’s Coronavirus Disease (COVID-19) evidence bundle.
The Medlior team reviewed the available evidence for virus-neutralizing monoclonal antibodies currently approved or under development as a treatment for SARS-CoV-2 infection, including evidence regarding their mechanisms of action, efficacy, safety and use as preventive therapies. The key findings from our review are below.
SARS-CoV-2 Spike Protein
COVID-19 is caused by the SARS-CoV-2 virus, which expresses a characteristic spike protein (or S protein) used to bind to receptors on host cells. Studies of plasma from patients who have been infected with SARS-CoV-2 have found neutralizing antibodies for the S protein found that monoclonal antibodies targeting this protein may offer therapeutic treatment for COVID-19.
While most candidate therapeutics in development target a single site on the S protein, others include a cocktail of multiple monoclonal antibodies, each targeting different specific S protein sites, which may prevent waning efficacy and viral mutation.
Virus-Neutralizing Monoclonal Antibodies
Monoclonal antibodies are lab-grown molecules developed to activate the body’s immune system response to a specific pathogen. Virus-neutralizing monoclonal antibodies bind to a virus, preventing it from infecting host cells (i.e., neutralizing the virus) and activate the body’s immune response to clear the virus particles. Monoclonal antibody therapies are so-called because they contain identical antibodies that bind to a single site on the virus; polyclonal preparations contain a mix of antibodies that bind to multiple sites on the virus.
Twenty-two virus-neutralizing antibodies in various phases of clinical development were identified, including five that are either approved for use in Canada or in late-phase clinical development: bamlanivimab, REGN-COV2 (casirivimab + imdevimab), AZD442 (AZD8895 + AZD1061), VIR-7831 (GSK4182136), and CT-P59. These therapeutics are typically administered as single dose intravenous infusions, though some trials include subcutaneous or intramuscular injections.
Bamlanivimab (previously LY-Cov555) was the first virus-neutralizing monoclonal antibody to be approved for therapeutic use in Canada, done so on November 20, 2020, under Health Canada’s Interim Order, for use in patients with COVID-19 who are not yet hospitalized but at risk for serious illness. At the time of report publication, the United States Food and Drug Administration (FDA) had issued Emergency Use Agreements for both bamlanivimab and REGN-COV2.
Considerations for Therapeutic Treatment
New evidence is constantly emerging as these new therapeutics move through their clinical development, however, at the time of this report, none of the identified therapeutics had shown benefit when administered to people already hospitalized due to COVID-19.
While these virus-neutralizing monoclonal antibodies are showing early promise as treatment options for patients with COVID-19, especially among those who are at high risk of developing severe illness, there are limited data available regarding their safety and efficacy. Preliminary data should be considered carefully before adopting these therapeutics as treatment strategies.
A full version of the report can be found on CADTHs website: https://covid.cadth.ca/treatment/horizon-scan-virus-neutralizing-monoclonal-antibodies-against-sars-cov-2/