AstraZeneca has submitted a request to the US Food and Drug Administration (FDA) for an Emergency Use Authorization (EUA) for AZD7442, its long acting antibody (LAAB) combination, for prophylaxis of symptomatic COVID-19.
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If granted, AZD7442 would be the first LAAB to receive an EUA for COVID-19 prevention. It is the first LAAB with Phase III data demonstrating a statistically significant reduction in the risk of developing symptomatic COVID-19 compared to placebo.
In August, 2021, AstraZeneca announced high-level results from the PROVENT pre-exposure prophylaxis trial which showed AZD7442 reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval (CI): 46, 90), compared to placebo.
Importantly, the trial population included people with co-morbidities and who may be in need of additional protection from SARS-CoV-2 infection. Greater than 75% of participants in PROVENT presented with co-morbidities associated with an increased risk of severe disease or a reduced immune response to vaccination.
The trial accrued 25 cases of symptomatic COVID-19 at the primary analysis. AZD7442 was well-tolerated.
The EUA request filing includes safety and efficacy data from the PROVENT and STORM CHASER Phase III trials and the Phase I trial.
AZD7442 is a combination of two LAABs tixagevimab (AZD8895) and cilgavimab (AZD1061) derived from B-cells donated by convalescent patients after SARS-CoV-2 virus. Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein7 and were optimised by AstraZeneca with half-life extension and reduced Fc receptor and complement C1q binding.
The half-life extension more than triples the durability of its action compared to conventional antibodies and could afford up to 12 months of protection from COVID-19 following a single administration1-4; data from the Phase I trial show high neutralising antibody titres for at least nine months.
The reduced Fc receptor binding aims to minimise the risk of antibody-dependent enhancement of disease - a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.
AZD7442 is being studied in a comprehensive clinical trial programme for both prevention and treatment of COVID-19 in over 9,000 participants. In the Phase III PROVENT trial, AZD7442 reduced the risk of developing symptomatic COVID-19 by 77%, compared to placebo.
The trial included 5,197 participants in a 2:1 randomisation AZD7442 to placebo. The primary analysis was based on 5,172 participants who did not have SARS-CoV-2 infection at baseline. The LAAB was well tolerated and preliminary analyses show adverse events were balanced between the placebo and AZD7442 groups.
Other ongoing trials include TACKLE COVID-19, a Phase III mild to moderate COVID-19 outpatient treatment trial, and collaborator treatment trials in outpatient and hospitalised settings. ■