17 March 2022, London, UK: 07:00 GMT
Evidence shows efficacy and protection (estimated for at least six months) after one dose in high-risk populations*
AstraZeneca's Evusheld▼ (tixagevimab co-packaged with cilgavimab) is authorised by the Medicines and Healthcare products Regulatory Agency (MHRA) and is the first antibody combination for pre-exposure prophylaxis (PrEP) against COVID-19 licensed in Great Britain. The use of this medicine is for adults who are not currently infected with (or know exposure to) the COVID-19 virus and are unlikely to mount an adequate response to COVID-19 vaccination – including those for whom vaccination is not recommended.1
Tom Keith Roach, President, AstraZeneca UK, said: “Evusheld fills an urgent gap in the UK’s fight against COVID-19, providing protection for people for whom vaccination may not be effective and who are often amongst the most clinically vulnerable in society. We hope to see this critical medicine made available to UK patients as quickly as possible, in line with other countries.”
Hugh Montgomery, Professor of Intensive Care Medicine at University College London, said: “This announcement is really good news. Sensible public health actions with vaccination are the mainstay of protection for most individuals in the UK. However, for a considerable number in society with existing health problems, protection against the virus through vaccination is limited. Availability of this antibody medicine now offers an increased likelihood of pre-exposure protection, and all from a single, effective immunisation that can last for months."
Tixagevimab co-packaged with cilgavimab, formerly known as AZD7442, is a combination of two monoclonal antibodies given as separate sequential intramuscular (IM) injections.1
About 500,000 people in the UK are immunocompromised and may benefit from this medicine for pre-exposure prophylaxis of COVID-19.2 Nearly 40% of people with immunocompromised or immunosuppressed conditions mount a low or undetectable immune response after vaccination and approximately 11% fail to generate any antibodies.3 This includes people with blood cancers, those taking immunosuppressive drugs after an organ transplant or for conditions including multiple sclerosis and rheumatoid arthritis.3
The primary data from the ongoing PROVENT Phase III trial (which met its primary endpoint) showed a statistically significant reduction in the risk of developing symptomatic COVID-19 with AZD7442 compared to placebo. The trial has shown protection from the virus continuing for at least six months. The antibody was tolerated and follow-up is needed to establish the full duration of protection.1
Based on the primary analysis of 5,172 participants (AZD7442 n = 3,441 and saline placebo n = 1,731), the antibody combination demonstrated a 77% relative risk reduction (RRR) in incidence of symptomatic COVID-19 [95% Confidence Interval (CI) 46-90; p <0.001; 8/3,441 (0.2%) AZD7442 and 17/1,731 (1.0%) placebo], and 0.8% Absolute Risk Reduction (ARR) compared to placebo, with median follow-up time post-administration of 83 days.1,4
In a subsequent analysis, the antibody combination demonstrated an 83% RRR in the incidence of symptomatic COVID-19 [95% CI: 66-91; 11/3,441 (0.3%) AZD7442 and 31/1,731 (1.8%) placebo] and 1.5% ARR compared to placebo, after a median 6.5-month follow-up.1
No hospitalisation or deaths were seen in the treatment arm. In the placebo arm, there were five cases of severe COVID-19 and two COVID-19 related deaths. Adverse events were reported in 35% (1,221/3,461) of participants receiving AZD7442 and 34% (593/1,736) receiving placebo, with the vast majority being mild to moderate in nature. The most frequently reported adverse reaction in the pooled analysis was injection site reaction.4,5
*Available data indicate that tixagevimab and cilgavimab may be effective for pre-exposure prophylaxis for six months based on the variants prevalent during the study. The trial is ongoing and more data is being generated to establish an exact duration of prophylactic protection. It is not known how pseudovirus or authentic SARS-CoV-2 neutralisation susceptibility data correlate with clinical outcome however data across multiple independent studies (pseudovirus and authentic ‘live’ virus) show that the anitbody combination retained neutralising activity against Omicron.6,7,8
MHRA licence terms and Adverse Event reporting
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. As part of the terms of the Conditional Marketing Authorisation from the MHRA further efficacy and safety data will be submitted as available to the MHRA. Side effects should be reported. This includes any possible side effects not listed in the package leaflet. You can report side effects directly via the MHRA’s Yellow Card Scheme at https://yellowcard.mhra.gov.uk. By reporting side effects, you can help provide more information on the safety of the medicines. Side effects experienced after taking an AstraZeneca medicine can also be reported to AstraZeneca by visiting https://aereporting.astrazeneca.com/.
Anibody combination: tixagevimab co-packaged with cilgavimab
Formally known as AZD7442, Evusheld is a combination of two monoclonal antibodies - 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 protein9 and were optimised by AstraZeneca with half-life extension and reduced Fc receptor and complement C1q binding. The half-life extension more than tripled the durability of its action compared to conventional antibodies;10 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.11
The recommended dosage is 300 mg of the antibody combination, as 150 mg of tixagevimab and 150 mg of cilgavimab administered as separate sequential intramuscular injections. A higher dose of 600 mg of the antibody combination, as 300 mg of tixagevimab and 300 mg of cilgavimab, may be more appropriate for some SARS-CoV-2 variants (for example, Omicron BA.1, Omicron BA.1.1). The use of the antibody combination should be in accordance with official recommendations from the UK’s Depart of Health and Social Care.1
AstraZeneca 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. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.
AstraZeneca is based in six different locations across the UK, with its global headquarters in Cambridge. In the UK, almost 8,000 employees work in research and development, manufacturing, supply, sales and marketing. We supply 34 different medicines to the NHS, which treat more than one million UK patients every year. For more information, please visit www.astrazeneca.co.uk and follow us on Twitter @AstraZenecaUK.
For media questions please contact UKMediaRelations@astrazeneca.com
1. Summary of Product Charecterics, Evusheld (on file): To be available at www.medicines.org.uk/emc
2. Blood Cancer UK https://bloodcancer.org.uk/news/were-calling-on-the-government-to-postpone-lifting-restrictions-on-june-21/ [Last accessed: March 2022].
3. NIHR, OCTAVE TRIAL https://www.nihr.ac.uk/news/octave-trial-initial-data-on-vaccine-responses-in-patients-with-impaired-immune-systems/28529 [Last accessed: March 2022]
4. FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR EVUSHELD™ (tixagevimab co-packaged with cilgavimab) https://www.fda.gov/media/154701/download [Last accessed: March 2022]
5. Levin et al. LB5. PROVENT: Phase 3 Study of Efficacy and Safety of AZD7442 (Tixagevimab/Cilgavimab) for Pre-exposure Prophylaxis of COVID-19 in Adults. ID Week. 2021
6. Dejnirattisai W, et al. Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Available from: https://www.biorxiv.org/content/10.1101/2021.12.03.471045v2. [Last accessed: March 2022].
7. VanBlargan LA, et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by 2 several therapeutic monoclonal antibodies. Available from: https://www.biorxiv.org/content/10.1101/2021.12.15.472828v1.full.pdf [Last accessed March 2022.]
8. Zhou T., et al., Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529. bioRxiv, 2021: p. 2021.12.27.474307. Available from: https://www.biorxiv.org/content/10.1101/2021.12.27.474307v1 [Last accessed March 2022.
9. Dong J, et al. Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail. bioRxiv. 2021; doi: 10.1101/2021.01.27.428529.
10. Tixagevimab and cilgavimab (Evusheld) for pre-exposure prophylaxis of COVID-19. JAMA. 2022;327(4):384-385. doi:10.1001/jama.2021.24931
11. van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.