AZD7442 is the first LAAB with Phase 3 data to demonstrate benefit in both prophylaxis and treatment of COVID-19.
AstraZeneca submitted a request to the US Food and Drug Administration (FDA) last week for Emergency Use Authorisation for AZD7442 for prophylaxis of COVID-19.
Half-life extension triples durability of action
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 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 compared to conventional antibodies and could afford up to 12 months of protection from COVID-19 following a single administration; data from the Phase I trial show high neutralising antibody titres for at least nine months.
Phase 3 trial data
The Phase 3 ‘Tackle’ trial included 903 participants aged 18+ split equally between AZD7442 and placebo: with 90% were at high risk of progression to severe COVID-19, including those with co-morbidities (this included cancer, diabetes, obesity, asthma, or immunosuppression).
The primary analysis was based on 822 participants.
The trial met the primary endpoint, with a dose of 600mg of AZD7442 given by intramuscular (IM) injection reducing the risk of developing severe COVID-19 or death (from any cause) by 50% compared to placebo in outpatients who had been symptomatic for seven days or less.
The trial recorded 18 events in the AZD7442 arm (18/407) and 37 in the placebo arm (37/415).
AZD7442 reduced the risk of developing severe COVID-19 or death (from any cause) by 67% compared to placebo, with nine events in the AZD7442 arm (9/253) and 27 in the placebo arm (27/251).
The LAAB was generally well tolerated in the trial.
Hugh Montgomery, professor of Intensive Care Medicine at University College London, and the trial’s principal investigator, said: “With continued cases of serious COVID-19 infections across the globe, there is a significant need for new therapies like AZD7442 that can be used to protect vulnerable populations from getting COVID-19 and can also help prevent progression to severe disease. These positive results show that a convenient intramuscular dose of AZD7442 could play an important role in helping combat this devastating pandemic.”
Mene Pangalos, executive vice president, BioPharmaceuticals R&D, AstraZeneca, said: “These important results for AZD7442, our long-acting antibody combination, add to the growing body of evidence for use of this therapy in both prevention and treatment of COVID-19. An early intervention with our antibody can give a significant reduction in progression to severe disease, with continued protection for more than six months.”
AZD7442 is also being studied as a potential treatment for hospitalised COVID-19 patients as part of the National Institute of Health’s ACTIV-3 trial and in an additional collaborator hospitalisation treatment trial.
It 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.