IDWeek data reinforces AstraZeneca’s commitment to advance science in vaccines and immune therapies

Additional analyses from TACKLE Phase III treatment trial further demonstrate Evusheld’s potential to reduce COVID-19 severity and mortality.
Analysis of long-acting antibody Beyfortus across respiratory syncytial virus (RSV) season further underscores the potential of the investigational treatment to be the first and only single-dose preventative option for all infants.

AstraZeneca will showcase new data across its Vaccines and Immune Therapies portfolio at the 11^th annual IDWeek conference, 19 – 23 October 2022, reinforcing its commitment to deliver long-lasting immunity for millions of people globally. The Company is set to present seven abstracts at the event.^1-7

Data featuring Evusheld (tixagevimab and cilgavimab)^1-5 and Vaxzevria (ChAdOx1-S [Recombinant], formerly AZD1222)⁶ in COVID-19 and Beyfortus (nirsevimab), in respiratory syncytial virus (RSV)⁷ will be presented. Beyfortus has the potential to transform RSV protection as the first and only single-dose preventative option for the broad infant population, including those born healthy, at term, pre-term or with specific medical conditions. In September, Beyfortus received a positive opinion from The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency.

Iskra Reic, Executive Vice-President Vaccines and Immune Therapies, AstraZeneca, said: “In our work in Vaccines and Immune Therapies, AstraZeneca has the ambition to help provide long-lasting immunity for millions. This year at IDWeek, our data for Evusheld, our long-acting antibody for patients at high risk of hospitalisation and death from COVID-19, and Beyfortus, our investigational long-antibody for RSV, demonstrate our commitment to helping protect the most vulnerable, ensuring no one is left behind.”

Evusheld’s role in protecting against COVID-19

Data from three abstracts from the Phase III TACKLE trial of Evusheld in adults with mild to moderate COVID-19 will be presented, which include new analyses on the prevention of hospitalisation and death;¹ reduction in the severity and progression of COVID-19 symptoms;² and the susceptibility of treatment-emergent viral variants to Evusheld.³ Data on the activity of Evusheld against circulating SARS-CoV-2 variants and those identified in the Phase III PROVENT prophylaxis trial will also be presented.⁴

Pursuing a breakthrough in infant RSV care

New viral susceptibility data on Beyfortus data in infants up to 150 days post-dose will be presented during IDWeek.⁷ Beyfortus is the first investigational passive immunisation with the potential to help protect a broad infant population across the entire RSV season with a single dose.

Additional data on Vaxzevria

AstraZeneca will also present data on Vaxzevria, evaluating its impact on immune responses, viral shedding and symptom burden in breakthrough SARS-CoV-2 infection.⁶

Key AstraZeneca presentations during IDWeek 2022

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 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 protein⁸ and were optimised by AstraZeneca with half-life extension and reduction of Fc effector function and complement C1q binding.⁹ The half-life extension more than triples the durability of its action compared to conventional antibodies;^10-12 data from the PROVENT Phase III trial show protection lasting six months.¹³ 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.¹⁴

Results from the TACKLE Phase III trial published inThe Lancet Respiratory Medicine showed that Evusheld significantly reduced the relative risk of progressing to severe COVID-19 or death (from any cause) through day 29 compared to placebo in non-hospitalised patients with mild-to-moderate COVID-19.¹⁵ Evusheld was generally well-tolerated in the trial. 90% of participants were at high risk of progression to severe COVID-19 due to age or co-morbidities, including cancer, diabetes, obesity, chronic lung disease or asthma, cardiovascular disease or immunosuppression.¹⁵

Evusheld is authorised for use for pre-exposure prophylaxis (prevention) of COVID-19 in the US (emergency use), EU, Japan and many other countries. Evusheld is approved for treatment of those with risk factors for severe SARS-CoV-2 infection in the EU and Japan. Regulatory submissions are progressing for both prevention and treatment indications around the world.

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.

Vaxzevria (ChAdOx1-S [Recombinant], formerly AZD1222)

AstraZeneca COVID-19 vaccine was invented by the University of Oxford. It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.

Vaxzevria is a ‘viral vector’ vaccine, which means a version of a virus that cannot cause disease is used as part of the vaccine, leaving the body knowing how to fight it if it is exposed to the real virus later. This vaccine technology has been used by scientists over the past 40 years to fight other infectious diseases such as the flu, Ebola, and HIV.¹⁶

The vaccine has been granted a conditional marketing authorisation or emergency use in more than 125 countries. It also has Emergency Use Listing from the World Health Organization, which accelerates the pathway to access in up to 144 countries through the COVAX Facility.

Under a sub-license agreement with AstraZeneca, the vaccine is manufactured and supplied by the Serum Institute of India under the name COVISHIELD.

Beyfortus (nirsevimab)

Beyfortus (nirsevimab), an investigational long-acting antibody designed for all infants for protection against RSV disease from birth through their first RSV season with a single dose, is being developed jointly by AstraZeneca and Sanofi using AstraZeneca’s YTE technology.

Beyfortus has been developed to offer newborns and infants direct RSV protection via an antibody to help prevent lower respiratory tract infection caused by RSV. Monoclonal antibodies do not require the activation of the immune system to help offer timely, rapid and direct protection against disease.¹⁷ The recommended dose of Beyfortus is a single intramuscular injection of 50 mg for infants with body weight <5 kg and a single intramuscular injection of 100 mg for infants with body weight ≥5 kg.

Beyfortus has been granted regulatory designations to facilitate expedited development by several major regulatory agencies around the world. These include Breakthrough Therapy Designation by The China Center for Drug Evaluation under the National Medical Products Administration; Breakthrough Therapy Designation from the US Food and Drug Administration; access granted to the European Medicines Agency (EMA) PRIority Medicines (PRIME) scheme; and named “a medicine for prioritized development” under the Project for Drug Selection to Promote New Drug Development in Pediatrics by the Japan Agency for Medical Research and Development (AMED). The safety and efficacy of Beyfortus was evaluated under an accelerated assessment procedure by the EMA. Beyfortus has not been approved by any regulatory authority.

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

1. Hobbs, F D R, et al. Outpatient Treatment With the SARS-CoV-2–Neutralizing Antibody Combination AZD7442 (Tixagevimab/Cilgavimab) for Preventing COVID-19 Hospitalizations in the Phase 3 TACKLE Trial: AZD7442 TACKLE key secondary abstract for IDWeek 2022, Oct 19–23, 2022, Washington, DC, USA Submission deadline: May 4, 2022, 17.00 ET.
2. Campos J A S, et al. Impact of the SARS-CoV-2–Neutralizing Antibody Combination AZD7442 (Tixagevimab/Cilgavimab) on the Severity and Progression of COVID-19 Symptoms in the Phase 3 TACKLE Trial: AZD7442 TACKLE symptom severity abstract for IDWeek 2022, Oct 19–23, 2022, Washington, DC, USA Submission deadline: May 4, 2022, 17.00 ET.
3. Kijak G H, et al. Treatment-Emergent Viral Variants in the Phase 3 TACKLE Trial Investigating Efficacy and Safety of AZD7442 (Tixagevimab/Cilgavimab) for the Treatment of Mild to Moderate COVID-19 in Adults: AZD7442 TACKLE variant analysis abstract for IDWeek 2022, Oct 19–23, 2022, Washington, DC, USA Submission deadline: May 4, 2022, 17.00 ET.
4. Tuffy K ea. AZD7442 (Tixagevimab/Cilgavimab) Demonstrates Potent In Vitro Activity Against SARS-CoV-2 Spike Variants Identified in Circulation and in Prophylaxis Clinical Studies: pVNT study abstract for IDWeek 2022, Oct 19–23, 2022, Washington, DC, USA Submission deadline: May 4, 2022, 17.00 ET.
5. Herbert A S, et al. Prophylactic and Therapeutic Activity of AZD7442 (Tixagevimab/Cilgavimab) in SARS-CoV-2 Hamster Challenge Models: Hamster challenge abstract for IDWeek2022, Oct 19–23, 2022, Washington, DC, USA Submission deadline: May 4, 2022, 17.00 ET.
6. Sobieszczyk M E, et al. IDWeek 2022 Abstract October 19th–23rd 2022, Washington DC, USA. Title: Immune responses, viral shedding, and COVID-19 symptom burden from breakthrough SARS-CoV-2 infection in a 2:1 randomized, double-blind, placebo-controlled Phase 3 study of AZD1222 (ChAdOx1 nCoV-19) vaccination: IDWeek 2022 Abstract October 19th–23rd 2022, Washington DC, USA.
7. Abram M ea. Pooled analysis of nirsevimab resistance through 150 days post dose in preterm and term infants: IDWeek 2022 Oral Presentation October 19th–23rd 2022, Washington DC, US.
8. Dong J et al. Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail. bioRxiv 2021.
9. Loo Y-M et al. The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans. Sci Transl Med 2022; 14(635): eabl8124.
10. 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).
11. 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.
12. 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):886–92.
13. Levin MJ et al. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. N Engl J Med 2022; 386(23):2188–200.
14. van Erp EA et al. Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease. Front Immunol 2019; 10:548.
15. Montgomery H et al. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine 2022.
16. Zhang et al. Adenoviral vector-based strategies against infectious disease and cancer. Available at: https://www.tandfonline.com/doi/full/10.1080/21645515.2016.1165908 Accessed October 2022.
17. Centers for Disease Control and Prevention (CDC). Vaccines & Immunizations:   https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm Accessed October 2022.