AstraZeneca's Evusheld (tixagevimab co-packaged with cilgavimab), a long-acting antibody combination for the prevention of COVID-19, retains neutralisation activity against the Omicron SARS-CoV-2 variant (B.1.1.529), according to new authentic `live' virus neutralisation data from both University College Oxford, UK and Washington University School of Medicine, St. Louis, US.

The findings were posted online on bioRxiv, a preprint server, here (https://www.biorxiv.org/content/10.1101/2021.12.03.471045v2) and here (https://www.biorxiv.org/content/10.1101/2021.12.15.472828v1).

Evusheld's Inhibitory Concentration 50 (IC50), a measure of neutralising potency of an antibody, was 273 ng/ml and 147 ng/ml in the Oxford and Washington University studies, respectively.[1,2] The levels are within the range of neutralising antibody titres found in individuals who have been previously infected with and recovered naturally from COVID-19.[3]

The data were generated from laboratory testing using actual live virus isolated from individuals who contracted the Omicron variant of COVID-19, considered a `gold standard' for antibody neutralisation studies.[4] Evusheld is one of only two antibody therapies authorised for use that showed neutralising activity against Omicron and against all other variants of concern in these two studies.[1,2]

These findings are in line with pseudovirus neutralising data from independent investigators at the US Food and Drug Administration (FDA) announced on 16 December[ ]2021 (https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/evusheld-long-acting-antibody-combination-retains-neutralising-activity-against-omicron-variant-in-independent-fda-study.html/), and add to the growing body of preclinical evidence demonstrating that Evusheld retains activity against all tested SARS-CoV-2 variants of concern to date.[5]

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "Consistent data across three independent studies now provide confidence that Evusheld, a combination of two highly potent antibodies, retains neutralising activity against the Omicron variant at a level that will continue to provide benefit to patients. Evusheld is the only antibody therapy authorised for pre-exposure prophylaxis of COVID-19 in the US, and we're excited that Evusheld is now available to help protect vulnerable populations, such as the immunocompromised, who are unable to mount an adequate response to vaccination and who remain at high-risk for COVID-19."

By combining two particularly potent antibodies with different and complementary activities against the virus, Evusheld was designed to evade potential resistance with the emergence of new SARS-CoV-2 variants.

The Omicron variant was not in circulation during the Evusheld clinical trials. The Company is continuing to collect further data to better understand the implications of these data in clinical practice. Data from both studies will be submitted for publication in a peer-reviewed journal.

Evusheld received Emergency Use Authorisation (EUA) in the US in December 2021 (https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/evusheld-long-acting-antibody-combination-authorised-for-emergency-use-in-the-us-for-pre-exposure-prophylaxis-prevention-of-covid-19.html) 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.

About 2% of the global population is considered at increased risk of an inadequate response to a COVID-19 vaccine.[6,7] Recent emerging evidence indicate that protecting vulnerable populations from getting COVID-19 could help prevent viral evolution that is an important factor in the emergence of variants.[8]

Notes

Evusheld

Evusheld, formerly known as 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 (https://www.astrazeneca.com/media-centre/articles/2020/advancing-our-discovery-of-novel-coronavirus-neutralising-antibodies-against-covid-19.html), the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein[9] 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 administration;[10-12 ]data from the Phase III PROVENT trial show protection lasting at least six months.[13] 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.[14 ]Evusheld is delivered as an IM dose of 150mg tixagevimab and 150mg cilgavimab administered in two separate, consecutive injections.

In December 2021, the FDA issued an EUA (https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/evusheld-long-acting-antibody-combination-authorised-for-emergency-use-in-the-us-for-pre-exposure-prophylaxis-prevention-of-covid-19.html) for the use of Evusheld for the pre-exposure prophylaxis (prevention) of COVID-19. It is the only antibody authorised in the US to prevent COVID-19 symptoms before virus exposure. Evusheld is also authorised for emergency use for prevention of COVID-19 in several other countries.

In August 2021, AstraZeneca announced (https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html) that Evusheld demonstrated a statistically significant reduction in the risk of developing symptomatic COVID-19 in the PROVENT trial; efficacy was 83% compared to placebo in a six-month analysis announced (https://www.astrazeneca.com/media-centre/press-releases/2021/new-analyses-of-two-azd7442-covid-19-phase-iii-trials-in-high-risk-populations-confirm-robust-efficacy-and-long-term-prevention.html) on 18 November 2021. In October 2021, AstraZeneca announced (https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-phiii-trial-positive-in-covid-outpatients.html) positive high-level results from the Evusheld TACKLE Phase III outpatient treatment trial. Evusheld 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 (https://clinicaltrials.gov/ct2/show/NCT04501978) and in an additional collaborator hospitalisation treatment trial.

Evusheld 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.

Under the terms of the licensing agreement with Vanderbilt, AstraZeneca will pay single-digit royalties on future net sales.

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com (https://www.astrazeneca.com/media-centre/press-releases/2021/twitter.com/AstraZeneca) and follow the Company on Twitter @AstraZeneca (https://www.astrazeneca.com/media-centre/press-releases/2021/twitter.com/AstraZeneca).

Contacts

For details on how to contact the Investor Relations Team, please click here (https://www.astrazeneca.com/investor-relations.html#Contacts). For Media contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html).

References

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3. Neerukonda SN et al. Establishment of a well-characterized SARS-CoV-2 lentiviral pseudovirus neutralization assay using 293T cells with stable expression of ACE2 and TMPRSS2. PLoS ONE. 2021.16(3): e0248348.  Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248348 [Last accessed: December 2021].
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13. AstraZeneca news release. New analyses of two AZD7442 COVID-19 trials in high-risk populations confirm robust efficacy and long-term prevention.  Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/new-analyses-of-two-azd7442-covid-19-phase-iii-trials-in-high-risk-populations-confirm-robust-efficacy-and-long-term-prevention.html. [Last accessed: December 2021].
14. van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.