AstraZeneca to seek regulatory approval for COVID-19 prevention antibody

AZD7442 is the first antibody combination (non-vaccine) modified to potentially provide long-lasting protection that has demonstrated prevention of COVID-19 in a clinical trial. It is a combination of two LAABs - tixagevimab (AZD8895) and cilgavimab (AZD1061) - derived from B-cells donated by convalescent patients after SARS-CoV-2 virus.

The antibody combination could help provide extra protection to high risk people who are unable to be vaccinated or have an inadequate response to vaccination.

In June, AstraZeneca announced that a parallel Phase 3 Storm Chaser trial for AZD7442 did not meet the primary endpoint of post-exposure prevention of COVID-19. But today it revealed that the Phase 3 Provent pre-exposure trial achieved a statistically significant reduction in the incidence of symptomatic COVID-19, thus meeting this trial's primary endpoint. 

AstraZeneca is now preparing regulatory submission of the prophylaxis data to health authorities for potential emergency use authorisation or conditional approval.

'This could be an important tool in our arsenal to help people who may need more than a vaccine'

AZD7442 was 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 have been optimised by AstraZeneca with half-life extension and reduced Fc receptor and complement C1q binding.

This 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 administration, according to AstraZeneca. Preliminary in vitro findings suggest AZD7442 neutralises virus variants, including Delta.

AZD7442 is being studied for both prevention and treatment of COVID-19; via both IM and intravenous administration routes.

The Phase 3 Provent trial assessed the safety and efficacy of a single 300mg dose in a pre-exposure prophylaxis trial.

The trial included 5,197 participants in a 2:1 randomisation AZD7442 to placebo, with participants in 87 sites across the US, UK, Spain, France and Belgium. A total of 25 cases of symptomatic COVID-19 were accrued at the primary analysis; with no cases of severe COVID-19 in the group treated with AZD7442. The placebo arm had three cases of severe COVID-19, including two deaths.

Participants were adults aged 18+ who had increased risk of inadequate response to vaccination; or increased risk of contracting the virus. Around 43% of the participants were aged 60+. More than 75% of participants had co-morbidities, which included conditions that have been reported to cause a reduced immune response to vaccination or an increased risk for severe COVID-19.

The LAAB was well tolerated and preliminary analyses show adverse events were balanced between the placebo and AZD7442 groups.

“The Provent data show that one dose of AZD7442, delivered in a convenient intramuscular form, can quickly and effectively prevent symptomatic COVID-19,”​ said Myron J. Levin, MD, Professor of Pediatrics and Medicine, University of Colorado School of Medicine, US, and principal investigator on the trial. “With these exciting results, AZD7442 could be an important tool in our arsenal to help people who may need more than a vaccine to return to their normal lives.”​

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, added: “We need additional approaches for individuals who are not adequately protected by COVID-19 vaccines. We are very encouraged by these efficacy and safety data in high-risk people, showing our long-acting antibody combination has the potential to protect from symptomatic and severe disease, alongside vaccines.”​

Further data from the AZD7442 Phase 3 trial will be published later this year.

Learnings from Storm Chaser

In June, AstraZeneca announced that a parallel Phase 3 trial, Storm Chaser, did not meet the primary endpoint of post-exposure prevention of symptomatic COVID-19. However, it did suggest AZD7442 reduced the risk of developing symptomatic COVID-19 by 73%, pivoting the focus onto the pre-exposure prevention trial.

AZD7442 is also being studied in the Tackle COVID-19 Phase 3 treatment trial 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.