Evusheld long-acting antibody combination retains neutralising activity against Omicron variants BA.4 and BA.5, according to new study from University of Oxford

Evusheld long-acting antibody combination retains neutralising activity against Omicron variants BA.4 and BA.5, according to new study from University of Oxford

In vitro data on new emerging Omicron variants consistent with Evusheld’s neutralisation activity against previous variants of concern

AstraZeneca’s Evusheld (tixagevimab and cilgavimab, formerly AZD7442) retains neutralisation activity against the emerging Omicron BA.4 and BA.5 (BA.4/5) variants, according to new preclinical pseudovirus assay data from the University of Oxford.1

The findings were reported online on bioRxiv, a preprint server.

These results are consistent with previous data from multiple studies showing that Evusheld retains potent neutralising activity against Omicron BA.2, the current dominant circulating variant, and neutralises all variants tested to date.2-6

Previously circulating SARS-CoV-2 variants have expanded in similar patterns; therefore it’s possible BA.4 and BA.5, which are now the dominant variants in Africa, could spread globally in a similar pattern to BA.2.6 BA.4 and BA.5 have identical S protein sequences and appear to have evolved from BA.2.1

John L. Perez, MD, MBA, MA, Senior Vice President, Head of Late Development, Vaccines & Immune Therapies, AstraZeneca, said: “By combining two antibodies with different and complementary activities against SARS-CoV-2, Evusheld was engineered from the start to outsmart the COVID-19 virus and to remain potent in the face of this virus’ ability to rapidly mutate. These findings further support Evusheld as an important option to help protect vulnerable populations such as the immunocompromised who are unable to respond adequately to COVID-19 vaccination and are at high risk for severe disease.”

Approximately 2% of the global population is considered at increased risk of an inadequate response to COVID-19 vaccination and may particularly benefit from pre-exposure prophylaxis (prevention) with Evusheld.7,8 This population includes people who are immunocompromised, such as cancer patients, transplant patients and anyone taking immunosuppressive medicines.3 People at increased risk of exposure to the SARS-CoV-2 virus could also benefit from protection with Evusheld.9 Emerging evidence indicates that protecting vulnerable populations from getting COVID-19 could help prevent viral evolution that is an important factor in the emergence of variants.10

Notes

Evusheld

Evusheld, formerly known as AZD7442, is a combination of two long-acting antibodies - tixagevimab (AZD8895) and cilgavimab (AZD1061) - derived from B-cells donated by individuals previously infected with the 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 protein11 and were optimised by AstraZeneca with half-life extension and reduced Fc receptor and complement C1q binding.12 The half-life extension more than triples the durability of its action compared to conventional antibodies;13-15 data from the Phase III PROVENT trial show protection lasting at least six months.16 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.17

There is a growing body of evidence from multiple independent in vitro and in vivo (animal model) studies supporting the potential of Evusheld to protect against Omicron SARS-CoV-2 subvariants.2-4,18,19 In particular, data from Washington University School of Medicine demonstrated Evusheld retained neutralising activity against the highly transmissible BA.2 subvariant, which is currently the dominant strain globally.2,6 This study also showed that Evusheld reduced viral burden and limited inflammation in the lungs (in vivo) for Omicron BA.1, BA.1.1 and BA.2.2

Evusheld has marketing authorisation in the European Union and was granted conditional marketing authorisation by the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain for pre-exposure prophylaxis of COVID-19. Evusheld is authorised for emergency use for pre-exposure prophylaxis of COVID-19 in the US. Evusheld is also authorised for use and being supplied in several other countries around the world. Regulatory filings are progressing in both prevention and treatment around the world.

The primary data supporting the Evusheld authorisations are from the ongoing PROVENT Phase III pre-exposure prevention trial, which showed a statistically significant reduction in the risk of developing symptomatic COVID-19 compared to placebo, with protection from the virus continuing for at least six months.16

In October 2021, AstraZeneca announced positive high-level results from the TACKLE Phase III outpatient treatment trial in which Evusheld provided statistically and clinically significant protection against the development of severe COVID-19 or death from any cause compared to placebo.20 Evusheld was generally well-tolerated in the trials.16,20

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 and follow the Company on Twitter @AstraZeneca.

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References

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