AstraZeneca Canada Files for Health Canada Authorization of AZD7442 for Prevention Of COVID-19

MISSISSAUGA, ON, Nov. 3, 2021 /CNW/ - AstraZeneca Canada has initiated a rolling review New Drug Submission with Health Canada for authorization of AZD7442, its long-acting antibody (LAAB) combination, for prevention of symptomatic COVID-19.

If granted, AZD7442 would be the first LAAB to receive Health Canada authorization for COVID-19 prevention.

"AZD7442 is the first LAAB with Phase III data demonstrating a statistically significant reduction in the risk of developing symptomatic COVID-19 compared to placebo. This is an important option, especially for vulnerable populations like those who are immune-compromised and often aren't able to mount a protective response following vaccination," said Dr. Alex Romanovschi, Vice President, Scientific Affairs, AstraZeneca Canada. "With this Health Canada filing, we are one step closer to providing an additional long-lasting option to help protect against COVID-19 alongside vaccines."

In August 2021, AstraZeneca announced high-level results from the PROVENT pre-exposure prophylaxis trial, which showed AZD7442 reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval (CI): 46, 90), compared to placebo. Importantly, the trial population included people with co-morbidities and who may be in need of additional protection from SARS-CoV-2 infection. Greater than 75% of participants in PROVENT presented with co-morbidities associated with an increased risk of severe disease or a reduced immune response to vaccination. The trial accrued 25 cases of symptomatic COVID-19 at the primary analysis. AZD7442 was well-tolerated.

AZD7442 was optimized using AstraZeneca's proprietary YTE half-life extension technology which more than triples the durability of its action compared to conventional antibodies.^1-4

Preliminary 'in vitro' findings demonstrate that AZD7442 demonstrates broad anti-COVID activity, and in particular neutralizes recent emergent SARS-CoV-2 viral variants, including the Delta and Mu variants.^5,6

About AZD7442
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 protein⁷ 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;^1-4 data from the Phase I trial show high neutralizing antibody titres for at least nine months.⁸ 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.⁹

AZD7442 is being studied in a comprehensive clinical trial program for both prevention and treatment of COVID-19 in over 9,000 participants. In the Phase III PROVENT trial, AZD7442 reduced the risk of developing symptomatic COVID-19 by 77%, compared to placebo. The trial included 5,197 participants in a 2:1 randomization AZD7442 to placebo. The primary analysis was based on 5,172 participants who did not have SARS-CoV-2 infection at baseline. The LAAB was well tolerated, and preliminary analyses show adverse events were balanced between the placebo and AZD7442 groups.

In TACKLE,¹⁰ a Phase III mild-to-moderate COVID-19 outpatient treatment trial, AZD7442 met its primary endpoint demonstrating a 50% reduction in the risk of developing severe COVID-19 or death compared to placebo in outpatients who had been symptomatic for seven days or less.

Other ongoing trials include collaborator treatment trials in outpatient and hospitalized settings.

Data published in Nature in July 2020 showed that in preclinical experiments, the LAABs were able to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease.¹¹

About AstraZeneca Canada
AstraZeneca is a global, innovation-driven biopharmaceutical business with a focus on the discovery, development and commercialization of primary and specialty care medicines that transform lives. Our primary focus is on four important areas of healthcare: Cardiovascular, Renal and Metabolic disease; Oncology; Respiratory & Immunology; and Rare Diseases. AstraZeneca operates in more than 100 countries and its innovative medicines are used by millions of patients worldwide. In Canada, we employ roughly 1,090 employees across the country and our headquarters are located in Mississauga, Ontario. For more information, please visit the company's website at www.astrazeneca.ca.

References
1.	Robbie GJ, et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrobial Agents and Chemotherapy. 2013; 57 (12): 6147-53.
2.	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. Antimicrobial Agents and Chemotherapy. 2017; 61(3): e01714-16.
3.	Yu XQ, et al. Safety, tolerability, and pharmacokinetics of MEDI4893, an investigational, extended-half-life, anti-staphylococcus aureus alpha-toxin human monoclonal antibody, in healthy adults. Antimicrobial Agents and Chemotherapy. 2016; 61 (1): e01020-16.
4.	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. The Pediatric Infectious Disease Journal. 2018; 37(9): 886-892.
5.	Wang L et al. Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Science. 2021 Jul 1. doi: 10.1126/science.abh1766.
6.	ACTIV. National Center for Advancing Translational Sciences OpenData Portal. SARS-CoV-2 Variants & Therapeutics, All Variants Reported in vitro Therapeutic Activity. Available at: https://opendata.ncats.nih.gov/variant/activity [Last accessed: September 2021].
7.	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.
8.	Loo Y-M, et al. AZD7442 demonstrates prophylactic and therapeutic efficacy in non-human primates and extended half-life in humans. medRxiv. Cold Spring Harbor Laboratory Press; 2021 [preprint] Available from: https://www.medrxiv.org/content/10.1101/2021.08.30.21262666v1.
9.	van Erp EA, et al. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease. Front Immunol. 2019; 10: 548.
10.	Clinicaltrials.gov. Phase III study of AZD7442 for treatment of COVID-19 in outpatient adults (TACKLE). Available at: https://clinicaltrials.gov/ct2/show//NCT04723394. [Last accessed: 30 June 2021].
11.	Zost SJ, et al. Potently neutralizing and protective human antibodies against SARS-CoV 2. Nature. 2020; 584: 443–449.

SOURCE AstraZeneca Canada Inc.

Mary-Anne Cedrone, AstraZeneca Canada, E-mail: [email protected]