In drug development, Phase 3 involves testing a medication against a group of human patients with the condition the medication is meant to treat. This is usually done comparatively against control groups taking other treatments for the same disease. Phase 3 is generally one of the last steps before a drug is verified safe by the United States Food and Drug Administration (FDA) and subsequently brought to market. For some products, this testing and validation timeline is sped up based on the spread and mutation of a virus.
COVID-19 and Antibody Treatments
Antibody treatments work by mimicking the natural function of our immune system. Antibodies are designed to target and bind to specific antigens — such as viruses — thereby neutralizing them. An antibody treatment can be monoclonal (derived from a single parent cell) or polyclonal, which refers to an antibody treatment based on multiple cells that all target the same antigen through different epitopes or protein structures. These epitopes are often a dual-edged sword from the perspective of a virus or other antigen. While they allow the antigen to bind to the cells they wish to attack, they also offer a ready target for antibody treatment. Those infamous spike proteins prominent on a COVID-19 model are an excellent contemporary example of an epitope.
Monoclonal antibodies have been identified as an effective treatment for COVID-19; one or more effective polyclonal antibody products may also be on the horizon. The multi-epitope targeting of polyclonal antibodies makes them well suited as a response to COVID-19 and its rapid mutations. They could represent a breakthrough in the testing, treatment, and containment of COVID-19’s existing variants and potential future iterations.
UT Southwestern Medical Center in Dallas, TX – Phase 3 National Trials for COVID-19 Polyclonal Antibody Treatments
SAB-185 is one of the promising polyclonal antibody-based treatments currently undergoing trials in hopes that it can get to market as a response to the Omicron variant and new emergent mutations of the COVID-19 virus. As of the beginning of 2022, the UT Southwestern Phase 3 trial was recruiting people at high risk of hospitalization due to COVID-19, such as the elderly and those who were unvaccinated.
National Institutes of Health ACTIV-2 Phase 3 Trials
The National Institutes of Health (NIH) have also supported Phase 3 testing of SAB-185 through their ACTIV-2 program, a unique initiative developed to fast-track treatments for COVID-19. This Phase 3 trial is sponsored by the NIH branch known as the National Institute of Allergy and Infectious Diseases. It will consist of a randomized study comparing SAB-185 against a cocktail of monoclonal antibodies (casirivimab and imdevimab, specifically) to test its efficacy in treating COVID-19 and reducing hospitalizations.
Other research continues to take place. Intravenous injection of heterologous polyclonal antibodies purified from animal plasma (plasma from horses, in this case) that has been “hyperimmunized” with SARS-CoV-2 proteins is another potentially promising method of using polyclonal antibodies to treat COVID-19 and its mutations. These intravenous preparations have been reliably used for years as antivenoms and rabies treatments. The technology and equipment to produce heterologous polyclonal antibodies have paved a promising path for future treatment options.
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