Builds on initial US government agreement, now totalling 1.7 million doses 

Only antibody therapy authorized in the US for pre-exposure prophylaxis of COVID-19 in people who are immunocompromised

AstraZeneca today announced the US Department of Health and Human Services has finalized its agreement to purchase an additional one million doses of EvusheldTM (150mg of tixagevimab co-packaged with 150mg of cilgavimab), a long-acting antibody combination for the pre-exposure prophylaxis (prevention) of COVID-19 in immunocompromised populations. 

This agreement includes the 500,000 additional dose purchase announced by the US government on January 12, 2022 and follows the government’s initial agreement for the purchase of 700,000 doses of Evusheld which are already being administered at sites around the US, for a total of 1.7 million doses. The US government has indicated that it plans to distribute these additional doses to states and territories at no cost. 

Ruud Dobber, Executive Vice President and President, BioPharmaceuticals Business Unit, AstraZeneca, said: “With continued cases of COVID-19 across the US and in the wake of the Omicron variant, there remains a critical need to provide additional protection to immunocompromised patients who are most vulnerable to the virus. We are proud to continue playing a leading role in the fight against COVID-19 with Evusheld, the first long-acting antibody combination to receive emergency use authorization in the US for pre-exposure prophylaxis of COVID-19 and the only antibody therapy authorized for this use, that shows neutralizing activity against Omicron and all other variants of concern to date.” 

Nitin Kapoor, Chairman and General Director, AstraZeneca Vietnam and Asia Area Frontier Markets said: “We are heartened by this good news which means that many more vulnerable patients in the US will get the extra protection they need against COVID-19. We are working closely with the Vietnam Ministry of Health on the necessary steps to accelerate the regulatory approval process, with a hope that the amount of Evusheld sign Vietnam Vaccine JSC (VNVC) could soon meet the needs of immunocompromised groups in Vietnam.”

Multiple independent live and pseudovirus studies showed that Evusheld retains neutralizing activity against the Omicron variant and all tested SARS-CoV-2 variants of concern to date.1-4 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. 

Evusheld received Emergency Use Authorization (EUA) in the US on December 8, 2021 for the pre-exposure prophylaxis (prevention) of COVID-19 in adults and adolescents (aged 12 and older who weigh 40kg or more) 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 due to a history of severe adverse reaction to a COVID-19 vaccine. 

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, the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein5 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;6-8 data from the Phase III PROVENT trial show protection lasting at least six months.9 The reduced Fc receptor binding aims to minimize the risk of antibody-dependent enhancement of disease – a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.10 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 for the use of Evusheld for the pre-exposure prophylaxis (prevention) of COVID-19. It is the only antibody authorized in the US to prevent COVID-19 symptoms before virus exposure. Evusheld is also authorized for emergency use for prevention of COVID-19 in several other countries. 

In August 2021, AstraZeneca announced 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 on November 18, 2021. In October 2021, AstraZeneca announced positive high-level results from the Evusheld TACKLE Phase III outpatient treatment trial. Evusheld is also being studied as a potential treatment for hospitalized COVID-19 patients as part of the National Institute of Health’s ACTIV-3 trial and in an additional collaborator hospitalization 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 is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization 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. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

References

 ACTIV. National Center for Advancing Translational Sciences Open Data Portal. SARS-CoV-2 Variants & Therapeutics, All Variants Reported in vitro Therapeutic Activity. Available at: https://opendata.ncats.nih.gov/variant/activity. [Last accessed: February 2022].

2 VanBlargan, L.A., Errico, J.M., Halfmann, P.J. et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat Med (2022). https://doi.org/10.1038/s41591-021-01678-y.

3 Dejnirattisai W, Huo J, Zhou D et al. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses, Cell, Volume 185, Issue 3, 2022, Pages 467-484.e15,

ISSN 0092-8674, https://doi.org/10.1016/j.cell.2021.12.046.

4 Takashita E, Kinoshita N, Yamayoshi et al. Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant. N Engl J Med. 2022 Jan 26. doi: 10.1056/NEJMc2119407. Epub ahead of print. PMID: 35081300.

5 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.

6 Robbie GJ, et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013; 57 (12): 6147-53.

7 Griffin MP, et al. Safety, tolerability, and pharmacokinetics of MEDI8897, the respiratory syncytial virus prefusion F-targeting monoclonal antibody with an extended half-life, in healthy adults. Antimicrob Agents Chemother. 2017; 61(3): e01714-16.

8 Domachowske JB, et al. Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. Pediatr Infect Dis J. 2018; 37(9): 886-892.

9 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: January 2022].

10 van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.