New preclinical authentic ‘live’ virus data from Washington University School of Medicine demonstrated that AZD7442 (tixagevimab co-packaged with cilgavimab) retains potent neutralising activity against the emerging and highly transmissible Omicron SARS-CoV-2 BA.2 subvariant.1 The data also showed that AZD7442 retains activity against Omicron BA.1 and BA.1.1.1
In addition, in vivo (live organism) data generated using mice infected with Omicron BA.1, BA.1.1 and BA.2 demonstrated that AZD7442 significantly reduced the viral burden and limited inflammation in the lungs for all three subvariants.1 SARS-CoV-2 viral load is associated with increased disease severity and mortality as well as post-COVID conditions (long COVID).2,3
The study used a transgenic mouse model to evaluate AZD7442 in pre-exposure prophylaxis (prevention) of COVID-19, similar to how AZD7442 is used in the clinic. These are the first in vivo data evaluating efficacy of AZD7442 against the Omicron variants versus previous in vitro neutralising activity assays in cultured cells.
The Washington University findings were reported online on bioRxiv, a preprint server.
Michael S. Diamond, MD, PhD, The Herbert S. Gasser Professor, Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University, US, said: “These new in vivo mouse model data confirm previous in vitro neutralisation activity results for AZD7442 against Omicron. The findings demonstrate that AZD7442 was effective at protecting against infection in the lungs, a critical disease site for severe COVID-19, across all Omicron subvariants tested.”
John Perez, Senior Vice President, Head of Late Development, Vaccines & Immune Therapies, AstraZeneca, said: “These important data show that AZD7442 reduced viral burden and limited inflammation caused by Omicron. The findings further support AZD7442 as a potential important option to help protect vulnerable patients such as the immunocompromised who could face poor outcomes if they were to become infected with COVID-19.”
Additional ‘live’ virus data from Aix-Marseilles University and pseudovirus data from the US Food and Drug Administration also demonstrated that AZD7442 neutralises BA.2.4,5 According to the World Health Organization, cases of BA.2 have been identified in 85 countries to date, with prevalence increasing in several parts of the world.6
AZD7442 is authorised for pre-exposure prophylaxis (prevention) of COVID-19 in the US and several other countries. AZD7442 is intended for vulnerable populations who have a medical condition or are receiving immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination, as well as those individuals for whom COVID-19 vaccination is not recommended. AZD7442 is not yet approved in the Philippines.
Notes
AZD7442
AZD7442, is a combination of two long-acting antibodies – tixagevimab (AZD8895) and cilgavimab (AZD1061) – derived from B-cells donated by convalescent patients after SARS-CoV-2 infection. 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 reduction of Fc effector function. The half-life extension more than triples the durability of its action compared to conventional antibodies;8-10 data from the Phase III PROVENT trial show protection lasting at least six months.11 The reduced Fc effector function 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.12
AZD7442 received Emergency Use Authorisation (EUA) in the US in December 2021 for the pre- exposure prophylaxis (prevention) of COVID-19 in people with moderate to severe immune compromise due to a medical condition or immunosuppressive medications and who may not mount an adequate immune response to COVID-19 vaccination, as well as those individuals for whom COVID-19 vaccination is not recommended, or have a history of severe adverse reactions to these vaccines. About 2% of the global population is considered at increased risk of an inadequate response to a COVID-19 vaccine.13,14
AZD7442 is also authorised for use and being supplied in several other countries around the world.
In the Philippines, AZD7442 has not yet
The primary data supporting the AZD7442 EUA are from the ongoing PROVENT Phase III pre-exposure prevention trial, which showed a statistically significant reduction (77% at primary analysis, 83% at median six-month analysis) in the risk of developing symptomatic COVID-19 compared to placebo, with protection from the virus continuing for at least six months.4 More follow-up is needed to establish the full duration of protection provided by AZD7442.
In October 2021, AstraZeneca announced positive high-level results from the TACKLE Phase III outpatient treatment trial in which a 600mg IM dose of AZD7442 was generally well-tolerated.4 AstraZeneca is discussing the TACKLE mild-to-moderate COVID-19 treatment data with health authorities.
AZD7442 was well-tolerated in the trials.
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 Defence; Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defence, under Contract No. W911QY-21-9-0001.
Under the terms of the licensing agreement with Vanderbilt, AstraZeneca will pay single-digit royalties on future net sales.
