AstraZeneca to Present Data on Vaccines and Immune Therapies Portfolio at ECCMID 2023

AstraZeneca to Present Data on Vaccines and Immune Therapies Portfolio at ECCMID 2023

(IN BRIEF) AstraZeneca is set to present data on its Vaccines and Immune Therapies portfolio at the European Congress of Clinical Microbiology & Infectious Diseases. Among the data to be presented will be details on the progress of AstraZeneca’s Vaccines and Immune Therapies portfolio, including its investigational long-acting COVID-19 antibody, AZD3152. AstraZeneca will present in vitro neutralization data on AZD3152, including activity against past and currently circulating COVID-19 variants. In addition, data will be presented from a 12-month analysis of the Phase III PROVENT prophylaxis trial. There will also be new data from the Phase II MUSIC trial, examining the safety profile and pharmacokinetics (PK) exposures in immunocompromised children aged less than two experiencing a first or second RSV season as part of the ongoing Beyfortus clinical trial programme.

(PRESS RELEASE) CAMBRIDGE, 15-Apr-2023 — /EuropaWire/ —AstraZeneca will highlight new data across its Vaccines and Immune Therapies portfolio at the 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), 15 – 18 April 2023, reinforcing its ambition to provide long-lasting immunity for millions of people globally. The company will present 15 abstracts, including four oral presentations, at the event.

Data featuring AZD3152, AstraZeneca’s investigational long-acting COVID-19 antibody, as well as Evusheld (tixagevimab and cilgavimab), Vaxzevria (ChAdOx1-S [Recombinant], formerly AZD1222) in COVID-19 and Beyfortus (nirsevimab) in respiratory syncytial virus (RSV) will be presented. Additional data on AstraZeneca’s growing vaccines and immune therapies pipeline against a variety of pathogens will also be presented.

Iskra Reic, Executive Vice President, Vaccines and Immune Therapies, AstraZeneca, said: “We are excited to share our data at ECCMID this year, reflecting the progress of our Vaccines and Immune Therapies portfolio and our ambition to deliver long-lasting immunity and protect against infectious diseases that affect millions of people around the world. COVID-19 remains of great concern and disproportionately impacts the immunocompromised. Our first in vitro data from our next generation long-acting antibody, AZD3152, show its potential to provide protection to the immunocompromised from all known COVID-19 variants of concern to date.”

The role of long-acting antibodies in protecting against COVID-19
AstraZeneca will present the first in vitro neutralisation data on AZD3152, including activity against past and currently circulating COVID-19 variants.1 An update on the ongoing SUPERNOVA Phase I/III trial evaluating AZD3152 for the prevention of symptomatic COVID-19 in an immunocompromised population will also be presented.2

Three abstracts from the Phase IV VALOR trial assessing real-world effectiveness of Evusheld in immunocompromised adults with mild-to-moderate COVID-19 will be presented, including new analyses on prevention of hospitalisation and death.3-5 Data from a 12-month analysis of the Phase III PROVENT prophylaxis trial will also be presented.6

Pursuing a breakthrough in infant RSV prevention

RSV is a common and highly contagious seasonal virus, infecting nearly all children by the age of two.7,8 As part of the ongoing Beyfortus clinical trial programme, new data from the Phase II MUSIC trial, examining the safety profile and pharmacokinetics (PK) exposures in immunocompromised children aged less than two experiencing a first or second RSV season, will be presented.9 This data adds to the existing body of evidence that reinforce Beyfortus’ consistent efficacy across endpoints and studies of approximately 70-80% efficacy against medically attended RSV Lower Respiratory Tract Disease (LRTD) vs placebo with a single dose.10-14

Additional data on Vaxzevria

AstraZeneca will also present data on its COVID-19 vaccine Vaxzevria, evaluating vaccine generated immunogenicity in the context of hybrid immunity from natural infection – an increasingly common occurrence.15-17

Key AstraZeneca presentations during ECCMID 2023

AZD3152

AZD3152 is an investigational next-generation long-acting antibody (LAAB). AZD3152 has been shown in in vitro studies to have broad and potent neutralising activity across all known SARS‑CoV-2 variants of concern to date.1 AZD3152 was derived from B-cells donated by convalescent patients after SARS-CoV-2 infection. AZD3152 was optimised with the same half-life extension and reduced Fc effector function and complement C1q binding as Evusheld. The extended half-life is expected to confer protection from COVID-19 for six months.18

The ongoing SUPERNOVA Phase I/III trial is evaluating the safety and neutralising activity of AZD3152 for the prevention of symptomatic COVID-19 in adults and adolescents 12 years of age or older. Participants have conditions that cause immune impairment and may not mount an adequate protective response after COVID-19 vaccination and, therefore, are at high risk of developing severe COVID-19 if they were to become infected. The trial is using a novel immunobridging approach to establish the safety and efficacy of AZD3152 building on the established generalised safety and efficacy of Evusheld. AZD3152 is anticipated to be available in 2H 2023, subject to regulatory reviews and trial readouts.

AstraZeneca licensed AZD3152 from RQ Biotechnology in May 2022. Under the licensing agreement, RQ Bio is eligible to receive single digit royalties on sales in addition to potential milestone payments.

Evusheld

Evusheld 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 protein19 and were optimised by AstraZeneca with half-life extension and reduction of Fc effector function and complement C1q binding.20 The half-life extension more than triples the durability of its action compared to conventional antibodies;21-23 data from the PROVENT Phase III trial show protection lasting six months.24 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.25

Evusheld is authorised in many countries around the world for both pre-exposure prophylaxis (prevention) and treatment of COVID-19.

Beyfortus (nirsevimab)

Beyfortus (nirsevimab) is a single dose long-acting antibody, developed and commercialised in partnership by AstraZeneca and Sanofi using AstraZeneca’s YTE technology. It is designed to protect infants entering or during their first respiratory syncytial virus (RSV) season and for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Beyfortus has been developed to offer newborns and infants direct RSV protection via an antibody to help prevent Lower Respiratory Tract Infections (LRTI) caused by RSV. Monoclonal antibodies do not require the activation of the immune system to help offer timely, rapid and direct protection against disease.26

In November 2022, Beyfortus was approved by the European Commission and by the UK Medicines and Healthcare products Regulatory Agency (MHRA) for the prevention of RSV LRTI disease in newborns and infants from birth during their first RSV season. 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.27,28

Beyfortus has also 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).

Sanofi Alliance

In March 2017, AstraZeneca and Sanofi announced an agreement to develop and commercialise nirsevimab. Under the terms of the agreement, AstraZeneca leads development and manufacturing activities, and Sanofi leads commercialisation activities and records revenue. Under the terms of the global agreement, Sanofi made an upfront payment of €120m, has paid development milestones of €55m and will pay up to €440m further milestones subject to achievement of certain development and sales-related milestones. The two companies share ex-US costs and profits. Revenue from the agreement is reported as Alliance Revenue and Collaboration Revenue in the Company’s financial statements. Following a revision to the profit-sharing arrangement relating to the development and commercialisation of nirsevimab in the US between AstraZeneca, Sanofi and Sobi, Sobi has entered into a direct relationship with Sanofi, replacing the previous participation agreement with AstraZeneca entered into in November 2018.

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.29

Vaxzevria is estimated according to model outcomes to have helped save over six million lives in the first year of vaccination (8 December 2020 to 08 December 2021).30 Vaxzevria is approved for COVID-19 primary vaccination schedule and first booster on top of a primary schedule in both homologous and heterologous settings, based on an acceptable risk-benefit profile.

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

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

References

1. Francica J et al. The SARS-CoV-2 monoclonal antibody AZD3152 potently neutralises historical and currently circulating variants. Poster presented at: 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID); 17 April 2023; Copenhagen, Denmark

2. Webber C et al. Trial in progress: a Phase I/III, randomised, modified double-blind, placebo- and active-controlled pre-exposure prophylaxis study of the SARS-CoV-2–neutralising antibody AZD3152 (SUPERNOVA). Poster presented at: 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID); 18 April 2023; Copenhagen, Denmark

3. Hayek S et al. Implementation of AZD7442 (tixagevimab/cilgavimab) COVID-19 pre-exposure prophylaxis (PrEP) in the largest HMO in Israel: real-world uptake and sociodemographic and clinical characteristics across immunocompromised patient groups. Poster presented at: 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID); 15 April 2023; Copenhagen, Denmark

4. Taylor S et al. Initial use of AZD7442 (tixagevimab/cilgavimab) for pre-exposure prophylaxis (PrEP) in severely immunocompromised patients in the United States: Prevention of deaths and underestimation of effectiveness due to misclassification of medically attended COVID-19. Poster presented at: 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID); 17 April 2023; Copenhagen, Denmark

5. DuVall S et al. Clinical effectiveness of AZD7442 (tixagevimab/cilgavimab) COVID-19 hospitalization among immunocompromised patients in the US Veterans Affairs health system: Overall and during periods of susceptible vs. resistant omicron variants. Poster presented at: 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID); 18 April 2023; Copenhagen, Denmark

6. Ustianowski A et al. Efficacy and safety of a single dose of AZD7442 (tixagevimab/cilgavimab) for prevention of COVID-19: 12-month analysis of the PROVENT phase 3 study. Oral presentation at: 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID); 18 April 2023; Copenhagen, Denmark

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8. Collins et al. Viral and host factors in human respiratory syncytial virus pathogenesis. Journal of Virology. 2008:2040–2055

9. Mankad VS et al. The safety and tolerability of nirsevimab for the prevention of RSV disease in immunocompromised children aged ≤24 months: the open label, Phase 2 MUSIC study. Oral presentation at: 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID); 16 April 2023; Copenhagen, Denmark

10. Hammitt LL, et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med. 2022;386 (9): 837-846

11. Clinicaltrials.gov. A Study to Evaluate the Safety and Efficacy of MEDI8897 for the Prevention of Medically Attended RSV LRTI in Healthy Late Preterm and Term Infants (MELODY). https://clinicaltrials.gov/ct2/show/NCT03979313. Accessed April 2023.

12. Clinicaltrials.gov. A Study to Evaluate the Safety and Efficacy of MEDI8897 for the Prevention of Medically Attended RSV LRTI in Healthy Preterm Infants. (MEDI8897 Ph2b). https://clinicaltrials.gov/ct2/show/results/NCT02878330. Accessed April 2023.

13. Griffin P, et al. Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants. N Engl J Med. 2020;383: 415-425

14. Simões E, et al.  Efficacy of nirsevimab against Respiratory Syncytial Virus lower respiratory Tract infections in preterm and term infants, and pharmacokinetic extrapolation to infants with congenital heart disease and chronic lung disease: A pooled analysis of randomised controlled trials. Lancet Child Adolesc Health. 2023;7(3):180-189

15. Jepson B et al. Persistently high immunogenicity and between-country differences driven by hybrid immunity from primary-series AZD2816 or AZD1222 (ChAdOx1 nCoV-19) and Omicron infection. Oral presentation at: 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID); 16 April 2023; Copenhagen, Denmark

16. Meeraus W et al. Relative effectiveness of a 2nd vs 1st COVID-19 vaccine booster against hospitalisation with severe acute respiratory syndrome (SARS) due to SARS-CoV-2 in high-risk individuals: a test-negative design case-control study (REFORCO) using Brazilian national data. Poster presented at: 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID); 17 April 2023; Copenhagen, Denmark

17. Bollaerts K et al. COVIDRIVE: the first public private partnership to conduct pan-European COVID-19 vaccine effectiveness studies. Poster presented at: 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID); 17 April 2023; Copenhagen, Denmark

18. AstraZeneca Data on File – REF173312

19. Dong J, et al. Genetic and structural Basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail. Nat Microbiol. 2021;6(10):1233-1244

20. Loo YM, et al. AZD7442 demonstrates prophylactic and therapeutic efficacy in non-human primates and extended half-life in humans. Sci Transl Med. 2022;14(635):eabl8124

21. 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):6147-6153

22. 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)

23. 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

24. Levin MJ, et al. Intramuscular AZD7442 (tixagevimab–cilgavimab) for prevention of Covid-19. N Engl J Med. 2022;386(23):2188-2200

25. van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus Infection and Disease. Front Immunol. 2019;10(MAR)

26. Centers for Disease Control and Prevention. Vaccines & Immunizations. August 18, 2017. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm. Accessed April 2023.

27. European Commission. https://www.ema.europa.eu/en/documents/product-information/beyfortus-epar-product-information_en.pdf. Accessed April 2023.

28. Medicines & Healthcare products Regulatory Agency. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1119040/Marketing_authorisations_granted_1_-_14_November_2022.pdf. Accessed April 2023

29. 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 April 2023

30. AstraZeneca Data on file Ref – 156573. Data estimates based on model outcomes from separate analyses conducted by Airfinity and Imperial College, United Kingdom

Media Contacts:

Jacob Lund
Head of Global Media Relations
+44 (0)1223 344 800
global-mediateam@astrazeneca.com

SOURCE: AstraZeneca