Long-Acting Antibody Combination for Prophylaxis of Symptomatic COVID-19 Files for Authorization

UK-based AstraZeneca today announced it had 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 prevention 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.

AZD7442 is a combination of two LAABs - tixagevimab (AZD8895) and cilgavimab (AZD1061) - derived from B-cells donated by convalescent patients after a SARS-CoV-2 virus infection.

Furthermore, AZD7442 was optimized using AstraZeneca’s proprietary YTE half-life extension technology, which more than triples the durability of its action compared to conventional antibodies.

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 protein and were optimized 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 than conventional antibodies and could afford up to 12 months of protection from COVID-19 following a single administration. In addition, data from the Phase I trial show high neutralizing antibody titers for at least nine months. 

The reduced Fc receptor binding aims to minimize the risk of antibody-dependent enhancement of disease - a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease, says the Company.

Mene Pangalos, EVP, BioPharmaceuticals R&D, AstraZeneca, stated in a press release, “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.”

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, 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.

And preliminary ‘in-vitro’ findings demonstrate that AZD7442 demonstrates broad anti-COVID activity, and in particular, neutralizes 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 and other governments around the world, says the Company.

Cambridge, UK, is home to one of AstraZeneca’s three global R&D Centres, alongside Gothenburg and Gaithersburg, and plays a central role in our mission to deliver life-changing medicines to patients.