First Long-Acting Antibody Cocktail to Prevent COVID-19 Submitted for EUA
AstraZeneca submitted data to the U.S. Food and Drug Administration (FDA) for an Emergency Use Authorization (EUA) for AZD7442 for prevention of symptomatic COVID-19. AZD7442 is a long-acting antibody (LAAB) combination, a cocktail of tixagevimab and cilgavimab, both originating from B-cells donated by patients who recovered from COVID-19. If authorized, it will be the first long-acting antibody cocktail against COVID-19.
On August 20, the company announced positive high-level data from the PROVENT Phase III pre-exposure prophylaxis trial of AZD7442. The antibody cocktail demonstrated a statistically significant decrease in the incidence of symptomatic COVID-19, which was the study’s primary endpoint. In it, AZD7442 decreased the risk of developing COVID-19 by 77% compared to placebo. There were no cases of severe COVID-19 or COVID-19-related deaths in patients receiving the cocktail; however, in the placebo cohort, there were three cases of severe COVID-19, with two deaths.
The trial included 5,197 participants. More than 75% of the trial participants had comorbidities, including diseases that cause a decreased immune response to vaccines.
“Vulnerable populations such as the immunocompromised often aren’t able to mount a protective response following vaccination and continue to be at risk of developing COVID-19,” said Mene Pangalos, executive vice president, BioPharmaceuticals R&D, AstraZeneca. “With this first global regulatory filing, we are one step closer to providing an additional option to help protect against COVID-19 alongside vaccines. We look forward to sharing AZD7442 data for the treatment of COVID-19 later this year.”
AstraZeneca optimized the antibody cocktail via the company’s proprietary YTE half-life extension technology. This potentially offers up to 12 months of protection from COVID-19. It is dosed via intramuscular injection.
Earlier in vitro data from researchers at Oxford University and Columbia University found that AZD7442 neutralized SARS-CoV-2 variants, including the Delta and Mu variants.
Currently, AstraZeneca is in talks with the U.S. government and other governments globally over supply agreements.
The antibody cocktail is also being studied for the treatment of COVID-19, including the TACKLE COVID-19 Phase III study in mild-to-moderate COVID-19 outpatients and collaborator treatment studies in outpatient and hospitalized settings. The therapy was developed with support from the U.S. Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA) in partnership with the Department of Defense; Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense.
The primary antibody treatment used in the U.S. is Regeneron Pharmaceuticals’ REGEN-COV. It is also a cocktail of two monoclonal antibodies, casirivimab and imdevimab. It is authorized to treat mild-to-moderate COVID-19 in adults and children 12 years and older who weigh 40 kilograms or more. In June, the FDA updated its EUA for REGEN-COV for a lower dose of 1,200 mg, half of the original dose, based on several studies, including a Phase III trial where REGEN-COV decreased the risk of hospitalization or death by 70% in high-risk, non-hospitalized patients.
Another antibody product is Eli Lilly’s combination of bamlanivimab and esesevimab. In mid-April, the company requested the FDA revoke the EUA for its single bamlanivimab (BAM) monotherapy because it was less effective against the Gamma, Beta, Delta and Epsilon variants compared to the cocktail.