AstraZeneca asks U.S. authorisation of drug to prevent COVID-19October 5, 2021
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.
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.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “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. 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.”
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 company said.
The EUA request filing includes safety and efficacy data from the PROVENT and STORM CHASER Phase III trials and the Phase I trial.
AZD7442 was optimised using AstraZeneca’s proprietary YTE half-life extension technology which more than triples the durability of its action compared to conventional antibodies.
Preliminary ‘in vitro’ findings demonstrate that AZD7442 demonstrates broad anti-COVID activity, and in particular neutralises recent emergent SARS-CoV-2 viral variants, including the Delta and Mu variants.
Discussions regarding supply agreements for AZD7442 are ongoing with the US Government as well as other governments around the world.
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-19,10 a Phase III mild-to-moderate COVID-19 outpatient treatment trial, and collaborator treatment trials in outpatient and hospitalised settings.
AZD7442 is being developed with support from the US government, including federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority in partnership with the Department of Defense; Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, under Contract No. W911QY-21-9-0001.
Data published in Nature in July 2020 showed that in preclinical experiments, the LAABs were able to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease.
Under the terms of the licensing agreement with Vanderbilt, AstraZeneca will pay single-digit royalties on future net sales.